[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-triple-negative-breast-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-triple-negative-breast-carcinoma":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,20,0,[8,42,75,99,216,229,239,262,302,323,347,368,388,408,428,467,495,516,544,571],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100054011","phase-2-testing-the-addition-of-an-individualized-vaccine-to-durvalumab-and-tremelimumab-and-chemotherapy-in-patients-with-metastatic-triple-negative-breast-cancer-100054011",false,"NCT03606967","Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer","Randomized Phase 2 Clinical Trial of Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab + Neoantigen Vaccine vs. Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Patients must have a histologically confirmed diagnosis of metastatic invasive triple negative breast cancer. Patients with clinical and\u002For radiologic suspicion of metastatic TNBC can be consented prior to this confirmation.\n* Estrogen receptor (ER) and progesterone receptor (PR) less than Allred score of 3 OR less than 1% positive staining cells in the invasive component of the tumor.\n* HER2 negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+.\n* PD-L1 negative by a Clinical Laboratory Improvement Act (CLIA) approved laboratory using compatible assays appropriate for treatment decisions.\n* Patients may have measurable or evaluable disease.\n* Patients must be willing to undergo biopsy and have accessible lesions for a new biopsy, or they must have sufficient tissue available from a biopsy performed for standard of care (specifications below). If patient does not have enough archived tissue available, a new biopsy is required. A tumor specimen obtained from relapsed primary, metastatic, or locally advanced sites of disease (if applicable) must be submitted. Acceptable samples include core needle biopsies for deep tumor tissue (minimum 4 cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. Formalin-fixed, paraffin-embedded (FFPE) tumor specimens in paraffin blocks are preferred; FFPE tumor tissue sections on slides may be provided if sufficient material (15 x 10μ, unstained) is available. Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable.\n* No prior therapy for metastatic TNBC. Patients who have received taxane-based adjuvant therapy are required to have a disease-free interval of at least 12 months after completion of taxane therapy.\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of durvalumab (MEDI4736) and tremelimumab in combination with neoantigen vaccine in patients \\\u003C 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 1 (Karnofsky \\>= 60%).\n* Body weight \\> 30 kg.\n* Must have a life expectancy of at least 12 weeks.\n* Absolute neutrophil count \\>= 1,500\u002FmcL.\n* Platelets \\>= 100,000\u002FmcL.\n* Hemoglobin \\>= 9.0 g\u002FdL.\n* Serum bilirubin =\\\u003C 1.5 x institutional upper limit of normal.\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =\\\u003C 5 x institutional upper limit of normal.\n* Calculated creatinine clearance \\> 40 mL\u002Fmin by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.\n* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:\n\n  * Women \\\u003C 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).\n  * Women \\>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \\> 1 year ago, had chemotherapy-induced menopause with last menses \\> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).\n* The effects of durvalumab (MEDI4736) and tremelimumab and neoantigen vaccine on the developing human fetus are unknown. For this reason and because these agents may be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 180 days after completion of durvalumab (MEDI4736) and tremelimumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n* Human immunodeficiency virus (HIV)-positive patients are eligible provided they have a negative viral load, CD4 count \\> 250, and are on a stable antiretroviral regimen.\n* Ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity who have a close caregiver or legal guardian are also eligible with the consent of the caregiver\u002Fguardian.\n\nExclusion Criteria:\n\n* Patients who are not considered to be candidates for carboplatin + gemcitabine for first line therapy of their metastatic triple negative breast cancer are not eligible.\n* Patients who have had chemotherapy, radiotherapy (to more than 30% of the bone marrow), or biologic therapy within 30 days (42 days for nitrosoureas or mitomycin C) prior to entering the study.\n* Patients who have received prior immunotherapy for metastatic disease.\n* Patients who have not recovered from grade \\>= 2 adverse events due to prior anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.\n\n  * Patients with grade \\>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.\n* Patients with grade \\>= 2 endocrinological adverse events (AEs), (e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or diabetes mellitus), must have been on a stable dose of supplemental therapy for at least 2 weeks before screening to be eligible for this study, and the endocrinological AE must be stable in the opinion of the treating physician.\n* Patients who are receiving any other investigational agents or who have received an investigational agent within the last 30 days.\n* Receipt of live attenuated vaccination within 6 months prior to study entry or within 30 days of receiving durvalumab (MEDI4736) and tremelimumab.\n\n  * Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment.\n* Major surgical procedure within 28 days prior to the first dose of durvalumab (MEDI4736) and tremelimumab. Local surgery of isolated lesions for palliative intent is acceptable.\n* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab (MEDI4736) or tremelimumab. The following are exceptions to this criterion:\n\n  * Intranasal, inhaled, topical steroids or local steroid injections (e.g. intra-articular injection)\n  * Systemic corticosteroids at physiological doses which are not to exceed 10 mg\u002Fday of prednisone or an equivalent corticosteroid\n  * Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)\n  * Steroids for symptoms from brain metastases as defined.\n* Spinal cord compression or active brain metastases and\u002For carcinomatous meningitis. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to registration are eligible if they meet all of the following criteria:\n\n  * Residual neurological symptoms have resolved to grade =\\\u003C 2\n  * On stable doses of dexamethasone, if applicable and if acceptable in the opinion of the treating physician\n  * Follow-up MRI performed after surgery or completion of radiation therapy and prior to registration shows no new lesions.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab (MEDI4736) and tremelimumab. Known allergy, or history of serious adverse reaction to vaccines, such as anaphylaxis, hives or respiratory difficulty.\n* Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) \\>= 470 ms calculated from 3 electrocardiograms (ECGs) (within 15 minutes at 5 \\[+\u002F- 3\\] minutes apart).\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, evidence of any acute or chronic viral illness or disease, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Pregnant women are excluded from this study because durvalumab (MEDI4736) and tremelimumab has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab (MEDI4736) and tremelimumab, breastfeeding should be discontinued if the mother is treated with durvalumab (MEDI4736) and tremelimumab. These potential risks may also apply to other agents used in this study. A negative serum pregnancy test is required no more than 7 days before study entry.\n* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n* History of pneumonitis or interstitial lung disease.\n* History of active primary immunodeficiency.\n* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and tuberculosis \\[TB\\] testing in line with local practice), hepatitis B (known positive hepatitis B virus \\[HBV\\] surface antigen \\[HBsAg\\] result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \\[anti-HBc\\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).\n* The patient with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met:\n\n  * Patient has undergone potentially curative therapy for all prior malignancies.\n  * Patients have been considered disease free for at least 1 year (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).\n* Patients with a strong likelihood of non-adherence (such as difficulties in adhering to follow-up schedule due to geographic distance from the treatment facility) should not be knowingly registered.\n* History of allogeneic organ transplantation.","ALL","18 Years",{"count":19,"type":20},86,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","This phase II trial studies how well nab-paclitaxel, durvalumab, and tremelimumab with or without personalized synthetic long peptide vaccine (neoantigen vaccine) works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving nab-paclitaxel, durvalumab, and tremelimumab with or without neoantigen vaccine will work better in treating patients with triple negative breast cancer.",[26,27,28],"Anatomic Stage IV Breast Cancer AJCC v8","Invasive Breast Carcinoma","Metastatic Triple-Negative Breast Carcinoma","RECRUITING","2026-07-10",{"date":32,"type":33},"2026-07-13","ACTUAL",{"date":35,"type":33},"2021-04-13",{"date":37,"type":20},"2026-12-30",{"name":39,"class":40},"National Cancer Institute (NCI)","NIH",30,{"id":43,"slug":44,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":4,"eligibilityCriteria":48,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":49,"targetDuration":4,"studyType":21,"phases":51,"briefSummary":53,"conditions":54,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":68,"startDateStruct":69,"completionDateStruct":71,"leadSponsor":73,"locationsCount":74},"100053568","phase-1-testing-the-safety-of-the-combination-of-anti-cancer-drugs-cx-5461-pidnarulex-and-trastuzumab-deruxtecan-t-dxd-for-human-epidermal-growth-factor-receptor-2-her2-positive-solid-tumors-and-breast-cancer-100053568","NCT07137416","Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer","Phase 1b Study of Pidnarulex and Trastuzumab Deruxtecan in Patients With HER2 Expressing Solid Tumors","Inclusion Criteria:\n\n* DOSE ESCALATION PHASE ONLY: Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\n* DOSE EXPANSION PHASE ONLY: Participants must have histologically or cytologically confirmed invasive breast cancer, with either locally advanced or metastatic disease\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CX-5461 (pidnarulex) in combination with T-DXd in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL\n\n  * No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment\n* Platelets ≥ 100,000\u002FmcL\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (or ≤ 2 × institutional ULN in patients with documented Gilbert's syndrome)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) ≤ 3 × institutional ULN (or ≤ 5 × ULN in patients with liver metastases)\n* International normalized ratio (INR)\u002Fprothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN\n* Glomerular filtration rate (GFR) ≥ 60 mL\u002Fmin\u002F1.73 m\\^2 (using the Cockcroft-Gault equation for participants with creatinine levels above institutional ULN)\n* Patients must have had at least one prior line of cytotoxic chemotherapy. Patients can have received an unlimited number of additional lines of chemotherapy, targeted therapy, biologic therapy, or hormonal therapy. Patients must not have progressed on a prior anthracycline in the metastatic setting. Receipt of anthracycline in the (neo)adjuvant setting is allowed, provided that disease recurrence occurred later than 6 months after the completion of treatment\n* Prior poly (ADP-ribose) polymerase (PARP) inhibition is allowed\n* No specific germline mutation is required\n* DOSE ESCALATION PHASE ONLY:\n\n  * HER2-positive (IHC 3+) solid cancers,\n  * HR+ HER2 positive\u002Flow\u002Fultralow breast cancer or triple negative breast cancer (TNBC) HER2-low breast cancer, with HER2 positive defined by the current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines,\n  * HER2-low, with HER2-low defined as IHC 2+\u002Fin situ hybridization (ISH)-, IHC 1+\u002FISH-, or IHC 1+\u002FISH untested\n* DOSE EXPANSION PHASE ONLY:\n\n  * Either the primary invasive tumor and\u002For the metastasis must be:\n\n    * HER2-low, with HER2-low defined as IHC 2+\u002FISH-, IHC 1+\u002FISH-, or IHC 1+\u002FISH untested. Any estrogen receptor (ER) and progesterone receptor (PR) expression is permitted but must be known, or\n    * HR+ HER2-ultralow defined as IHC 0 with membrane staining\n* Participants must have at least one lesion that is not within a previously radiated field that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Bone lesions are not considered measurable by definition. Biopsy of the lesion that will be used for disease evaluation (measurable disease) is not allowed in the dose expansion portion of this study\n* Peripheral neuropathy grade ≤ 1\n* Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days before randomization\u002Fenrollment\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* The effects of CX-5461 (pidnarulex) and T-DXd on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) 14 days prior to study entry and for the duration of study participation and for at least 7 months (women of childbearing potential \\[WOCBP\\] only) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should not breastfeed while taking CX-5461 (pidnarulex) and T-DXd and for 7 months after cessation of treatment. Men treated or enrolled on this protocol must also agree to use adequate contraception 14 days prior to the study, for the duration of study participation, and 6 months after completion of CX-5461 (pidnarulex) and T-DXd administration\n* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\[FSH\\] \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory) or on ovarian suppression are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method\n* Male patients must not freeze or donate sperm starting at screening and throughout the study period, and at least 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study\n* Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives (LAR) may sign and give informed consent on behalf of study participants\n* Patients who have had chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic radiation therapy). These patients will be excluded because T-DXd is known to increase the risk of developing pneumonitis\n\nExclusion Criteria:\n\n* Patients with a history of (non-infectious) interstitial lung disease (ILD) that required steroids, have current ILD, or where there is suspected ILD that cannot be ruled out by imaging at screening. These patients will be excluded because T-DXd is known to increase the risk of developing ILD and pneumonitis\n* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy at the time of screening. These patients will be excluded because T-DXd is known to increase the risk of developing ILD and pneumonitis\n* Patients who have had chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer) within 3 weeks (2 weeks or five half-lives, whichever is longer for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents), weekly paclitaxel; 6 weeks for nitrosoureas or mitomycin C. These patients will be excluded to allow for recovery of toxicities related to chemotherapy and minimize risk of drug interactions\n* Patients who have had cancer immunotherapy including monoclonal antibody therapy within 4 weeks\n* Patients who have had a major surgery within 4 weeks\n* Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤ 1 or baseline. Patients with chronic grade 2 toxicities may be eligible (e.g., grade 2 chemotherapy-induced neuropathy). Patients should no longer be symptomatic nor require treatment with corticosteroids or anticonvulsants and must have recovered from the acute toxic effect of radiotherapy\n* Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of CX-5461 (pidnarulex) will be determined based on their potential to interact with the CYP3A4 isozyme. Specifically, subjects taking strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded from participation in the trial. A list of agents that interact with CYP450 isoenzymes is provided\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CX-5461 (pidnarulex), T-DXd, or the inactive ingredients in the drug products, including patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies\n* Patients with a corrected QT interval (QTc) prolongation to \\> 470 ms (females) or \\> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)\n* Patients with clinically significant corneal disease, cicatricial conjunctivitis or active ocular surface disease in the opinion of the investigator\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because CX-5461 (pidnarulex) and T-DXd are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with CX-5461 (pidnarulex) and T-DXd, breastfeeding should be discontinued if the mother is treated with CX-5461 (pidnarulex) and T-DXd and avoided for 7 months after the last dose",{"count":50,"type":20},36,[52],"PHASE1","This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients with breast cancer and other solid tumors that express varying levels of a protein called HER2 and that has spread from where it first started (primary site) to other places in the body (metastatic), that cannot be removed by surgery (unresectable), or that has spread to nearby tissue or lymph nodes (locally advanced). Pidnarulex is an enzyme inhibitor that causes cell death and prevents tumor cell growth. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving pidnarulex in combination with trastuzumab deruxtecan may be safe, tolerable and\u002For effective in treating patients with metastatic, unresectable, or locally advanced HER2-expressing breast cancer or other solid tumors.",[55,26,27,56,57,58,59,60,61,28,62,63,64,65,66,67],"Anatomic Stage III Breast Cancer AJCC v8","Locally Advanced Breast Carcinoma","Metastatic Breast Carcinoma","Metastatic HER2-Low Breast Carcinoma","Metastatic HER2-Positive Breast Carcinoma","Metastatic Hormone Receptor-Positive Breast Carcinoma","Metastatic Malignant Solid Neoplasm","Unresectable Breast Carcinoma","Unresectable HER2-Low Breast Carcinoma","Unresectable HER2-Positive Breast Carcinoma","Unresectable Hormone Receptor-Positive Breast Carcinoma","Unresectable Malignant Solid Neoplasm","Unresectable Triple-Negative Breast Carcinoma",{"date":32,"type":33},{"date":70,"type":20},"2026-10-05",{"date":72,"type":20},"2028-01-10",{"name":39,"class":40},2,{"id":76,"slug":77,"hasResults":11,"nctId":78,"briefTitle":79,"officialTitle":80,"acronym":4,"eligibilityCriteria":81,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":82,"targetDuration":4,"studyType":21,"phases":84,"briefSummary":85,"conditions":86,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":88,"lastUpdatePostDateStruct":89,"startDateStruct":91,"completionDateStruct":93,"leadSponsor":95,"locationsCount":98},"100498459","phase-2-circulating-tumor-dna-to-guide-changes-in-standard-of-care-chemotherapy-100498459","NCT05770531","Circulating Tumor DNA to Guide Changes in Standard of Care Chemotherapy","A Randomized Clinical Trial Comparing ctDNA-Directed Therapy Change With Standard of Care in Patients With Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Clinical stage IV (metastatic) estrogen receptor (ER), PR, HER2 negative invasive mammary carcinoma, previously documented by histological analysis and that meets the following criteria:\n\n  * HER2 negativity is defined as any of the following by local laboratory assessment:\n\n    * In-situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 \\\u003C 2.0 or\n    * Single probe average HER2 gene copy number \\\u003C 4 signals\u002Fcell), or\n    * Immunohistochemistry (IHC) 0 or IHC 1+ (if more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the sponsor-investigator to establish eligibility of the patient)\n  * ER and PR negativity are defined as =\\\u003C 10% of cells expressing hormonal receptors via IHC analysis\n* PD-L1 negative (combined positive score \\[CPS\\] \\\u003C 10) or otherwise not appropriate for checkpoint inhibitors\n* Patients must have measurable disease according to the standard RECIST version 1.1\n\n  \\* NOTE: CT scans or MRIs used to assess the measurable disease must have been completed with 28 days prior to the study drug initiation\n* Patients must be age \\>= 18 years; both male and female are eligible\n* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =\\\u003C 2\n* Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study\n* No prior chemotherapy regimens for metastatic disease\n* Absolute neutrophil count (ANC) \\>= 1000\u002Fmm\\^3 (obtained less than 28 days from initiation of study drug)\n* Platelet count \\>= 100,000\u002Fmm\\^3 (obtained less than 28 days from initiation of study drug)\n* Bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutatmic pyruvic transaminase (SGPT), alkaline phosphatase =\\\u003C 4x upper limits of normal if no liver metastases present\n* Serum total bilirubin must be \\\u003C 3x upper limits of normal for patients with Gilbert disease\n* Total bilirubin, SGOT, SGPT =\\\u003C 6x upper limits of normal if liver metastases present (obtained less than 28 days from initiation of study drug)\n* For patients who are not postmenopausal (women) or surgically sterile (absence of ovaries and\u002For uterus or vasectomy), agreement to remain abstinent or to use two adequate methods of contraception (e.g., condoms, diaphragm, vasectomy\u002Fvasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of study treatment. Hormone based oral contraceptives are not allowed on study. Postmenopausal is defined as:\n\n  * Age \\>= 55 years\n  * Age =\\\u003C 55 years and amenorrheic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression; or follicle stimulating hormone and estradiol in the postmenopausal range\n\nExclusion Criteria:\n\n* Leptomeningeal disease\n* Uncontrolled tumor-related pain: patients requiring narcotic pain medication must be on a stable regimen at registration. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to randomization\n* Uncontrolled hypercalcemia (\\> 1.5 mmol\u002FL ionized calcium or calcium \\> 12 mg\u002FdL or corrected serum calcium \\> upper limit of normal \\[ULN\\]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy\n* Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer)\n* Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biological therapy) other than the ones specified in the protocol\n* Women only: pregnancy or lactation\n* Evidence of significant uncontrolled concomitant disease that in the opinion of the investigator could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)\n* Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) \\\u003C 35% will be excluded. Patients with known coronary artery disease or congestive heart failure not meeting the above criteria must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate\n* Major surgical procedure within 4 weeks prior to randomization or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis. Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted\n* Psychiatric illness\u002Fsocial situations that would compromise patient safety or limit compliance with study requirements",{"count":83,"type":20},160,[23],"This phase II trial tests how well evaluating circulating tumor deoxyribonucleic acid (ctDNA) works to guide therapy-change decisions in treating patients with triple-negative breast cancer (TNBC) that has spread from where it first started (primary site) to other places in the body (metastatic). This study wants to learn if small pieces of DNA associated with a tumor (called circulating tumor DNA, or ctDNA) can be detected in investigational blood tests during the course of standard chemotherapy treatment for breast cancer, and whether information from such investigational ctDNA blood testing could possibly be used as an early indication of chemotherapy treatment failure. It is hoped that additional information from investigational blood testing for ctDNA could help doctors to switch more quickly from a standard chemotherapy treatment that typically has significant side effects and which may not be working, to a different standard treatment regimen against TNBC, called sacituzumab govitecan. Sacituzumab govitecan is a monoclonal antibody, called hRS7, linked to a chemotherapy drug, called irinotecan. hRS7 is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and delivers irinotecan to kill them. Studying ctDNA may assist doctors to change therapy earlier if needed, and may improve health outcomes in patients with metastatic TNBC.",[87,28],"Metastatic HER2-Negative Breast Carcinoma","2026-06-19",{"date":90,"type":33},"2026-06-24",{"date":92,"type":33},"2023-10-03",{"date":94,"type":20},"2028-10-01",{"name":96,"class":97},"Vanderbilt-Ingram Cancer Center","OTHER",1,{"id":100,"slug":101,"hasResults":11,"nctId":102,"briefTitle":103,"officialTitle":104,"acronym":105,"eligibilityCriteria":106,"healthyVolunteers":11,"sex":16,"minAge":107,"maxAge":4,"enrollmentInfo":108,"targetDuration":4,"studyType":21,"phases":110,"briefSummary":111,"conditions":112,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":207,"lastUpdatePostDateStruct":208,"startDateStruct":210,"completionDateStruct":212,"leadSponsor":214,"locationsCount":98},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958","NCT05269381","Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors","A Phase I\u002FII Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)","PNeoVCA","Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.\n\nPHASE I PRE-REGISTRATION, ALL:\n\n* Willing to provide tissue specimens per protocol\n\n  * NOTE: includes fresh tissue specimen at pre-registration for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo Institutional Review Board (IRB) protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration.\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n* Willing to provide blood specimens for research\n* Negative pregnancy test =\\\u003C 7 days prior to pre-registration for persons of childbearing potential. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).\n* The following lab values obtained =\\\u003C 28 days prior to pre-registration:\n\n  * Hemoglobin \\>= 9.0 g\u002FdL (Must be \\>= 7 days after most recent transfusion)\n  * Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 or \\>= 1.5 X 10\\^9\u002FL\n  * Platelet count \\>= 100,000\u002Fmm\\^3 or \\>= 100 X 10\\^9\u002FL (Must be \\>=7 days after most recent transfusion)\n  * Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) =\\\u003C 3 x ULN or =\\\u003C 5 x ULN with liver metastases\n  * Creatinine =\\\u003C 1.5 x ULN OR calculated creatinine clearance must be \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n  * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy\n\nPHASE I REGISTRATION, ALL:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood and tissue specimens for research\n* Willing to return to enrolling institution for follow-up\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only\n\n  * NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicity see specified limits for inclusion) or NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nPHASE II PRE-SCREENING COHORT 3 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \\\u003C 10%, progesterone receptor (PR) \\\u003C 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)\n* Evidence of residual disease \\>= 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-SCREENING COHORT 4 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of lung NSCLC\n* No actionable EGFR mutations and ALK fusions\n* Stage II or stage III based on AJCC 8th\n* Tumor \\>= 2 cm on pre-surgery evaluation imaging (residual disease \\>= 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed\n* Provide written informed consent\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 3 (TNBC) ONLY:\n\n* Histologically confirmed residual cancer burden 2 and 3 in surgical specimens\n\nPHASE II PRE-REGISTRATION COHORT 4 (NSCLC) ONLY:\n\n* Tumor without complete pathologic response is confirmed in pathology\n* Willing to proceed with surgery and provide tissue specimens for complete exome and transcriptome sequencing\n\n  * NOTE: Patients who had sequencing under certain Mayo IRB protocols and neoantigens identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration\n* Negative pregnancy test ≤7 days prior to pre-registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* ECOG PS of 0 or 1\n* Anticipated life expectancy \\> 6 months\n\nPHASE II REGISTRATION:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Patients will receive \\>= 2 additional cycles of maintenance pembrolizumab\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood specimens for research\n* Willing to return to enrolling institution for follow-up\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nExclusion Criteria\n\nALL PHASES:\n\n* Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:\n\n  * Pregnant person\n  * Nursing person unwilling to stop breast feeding\n  * Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle\n* Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens\n* History of myocardial infarction =\\\u003C 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy\n\nPHASE I PRE-REGISTRATION:\n\n* Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease\n  * Stroke =\\\u003C 3 months prior to pre-registration\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* History of active autoimmune disease (AD) that required systemic treatment in =\\\u003C 30 days (i.e., use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major Surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n  * Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent permitted in absence of active AD\n* Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \\>10 mg daily prednisone equivalent\n\n  * NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)\n\nPHASE II PRE-SCREENING:\n\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-screening\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n\nPHASE II PRE-REGISTRATION\n\n* Uncontrolled illness including, but not limited to:\n\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n* Patients will also be excluded based on tissue\u002Fribonucleic acid (RNA)\u002Fdeoxyribonucleic acid (DNA) quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are \\>= 2 cores with passing cellularity; (3) \\>= 30% of tumor RNA with fragment sizes are \\>= 200 base pairs (DV200 \\>= 30); (4) \\\u003C 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)\n\nPHASE II REGISTRATION\n\n* Evidence of metastatic disease or recurrence\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n\n    * NOTE: Continuation of pembrolizumab per standard of care is allowed\n    * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Requirement for systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in","16 Years",{"count":109,"type":20},132,[52,23],"This phase I\u002FII trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.",[55,113,114,115,26,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,61,154,155,156,157,28,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,66,197,198,199,200,67,201,202,203,204,205,206],"Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage III Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Merkel Cell Carcinoma AJCC v8","Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Cervical Carcinoma","Locally Advanced Endometrial Carcinoma","Locally Advanced Gastric Adenocarcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Locally Advanced Head and Neck Squamous Cell Carcinoma","Locally Advanced Hepatocellular Carcinoma","Locally Advanced Lung Non-Small Cell Carcinoma","Locally Advanced Malignant Solid Neoplasm","Locally Advanced Melanoma","Locally Advanced Merkel Cell Carcinoma","Locally Advanced Renal Cell Carcinoma","Locally Advanced Skin Squamous Cell Carcinoma","Locally Advanced Triple-Negative Breast Carcinoma","Locally Advanced Unresectable Breast Carcinoma","Locally Advanced Unresectable Cervical Carcinoma","Locally Advanced Unresectable Gastric Adenocarcinoma","Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma","Locally Advanced Unresectable Renal Cell Carcinoma","Locally Advanced Urothelial Carcinoma","Metastatic Cervical Carcinoma","Metastatic Endometrial Carcinoma","Metastatic Gastric Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Melanoma","Metastatic Merkel Cell Carcinoma","Metastatic Renal Cell Carcinoma","Metastatic Skin Squamous Cell Carcinoma","Metastatic Urothelial Carcinoma","Skin Squamous Cell Carcinoma","Stage III Cervical Cancer AJCC v8","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IIIA Cervical Cancer AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIA Lung Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIB Cervical Cancer AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IIIB Lung Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Lung Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Cervical Cancer AJCC v8","Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","Stage IVA Cervical Cancer AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVA Lung Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Cervical Cancer AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","Stage IVB Lung Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","Triple-Negative Breast Carcinoma","Unresectable Cervical Carcinoma","Unresectable Endometrial Carcinoma","Unresectable Gastric Adenocarcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","Unresectable Head and Neck Squamous Cell Carcinoma","Unresectable Hepatocellular Carcinoma","Unresectable Lung Non-Small Cell Carcinoma","Unresectable Melanoma","Unresectable Merkel Cell Carcinoma","Unresectable Renal Cell Carcinoma","Unresectable Skin Squamous Cell Carcinoma","Unresectable Urothelial Carcinoma","Breast Adenocarcinoma","Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","2026-06-18",{"date":209,"type":33},"2026-06-23",{"date":211,"type":33},"2022-03-31",{"date":213,"type":20},"2028-03-31",{"name":215,"class":97},"Mayo Clinic",{"id":217,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":218,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":219,"targetDuration":4,"studyType":21,"phases":221,"briefSummary":24,"conditions":222,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":223,"lastUpdatePostDateStruct":224,"startDateStruct":226,"completionDateStruct":227,"leadSponsor":228,"locationsCount":41},"100332337","Randomized Phase 2 Clinical Trial of Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab + Neoantigen Vaccine Vs. Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer",{"count":220,"type":20},70,[23],[26,27,28],"2026-06-11",{"date":225,"type":33},"2026-06-12",{"date":35,"type":33},{"date":37,"type":20},{"name":39,"class":40},{"id":230,"slug":4,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":4,"eligibilityCriteria":48,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":231,"targetDuration":4,"studyType":21,"phases":232,"briefSummary":53,"conditions":233,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":234,"lastUpdatePostDateStruct":235,"startDateStruct":236,"completionDateStruct":237,"leadSponsor":238,"locationsCount":74},"100603507",{"count":50,"type":20},[52],[55,26,27,56,57,58,59,60,61,28,62,63,64,65,66,67],"2026-06-10",{"date":223,"type":33},{"date":70,"type":20},{"date":72,"type":20},{"name":39,"class":40},{"id":240,"slug":241,"hasResults":11,"nctId":242,"briefTitle":243,"officialTitle":244,"acronym":4,"eligibilityCriteria":245,"healthyVolunteers":11,"sex":246,"minAge":17,"maxAge":4,"enrollmentInfo":247,"targetDuration":4,"studyType":21,"phases":249,"briefSummary":250,"conditions":251,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":253,"lastUpdatePostDateStruct":254,"startDateStruct":256,"completionDateStruct":258,"leadSponsor":260,"locationsCount":74},"100496202","phase-2-propranolol-and-pembrolizumab-for-tumor-re-sensitization-and-treatment-of-patients-with-checkpoint-inhibitor-refractory-metastatic-or-unresectable-triple-negative-breast-cancer-100496202","NCT05741164","Propranolol and Pembrolizumab for Tumor Re-sensitization and Treatment of Patients With Checkpoint Inhibitor Refractory Metastatic or Unresectable Triple Negative Breast Cancer","Impact of Beta-2 Adrenergic Blockade With Checkpoint Inhibition in Checkpoint Inhibitor Refractory Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Age \\>= 18 years of age\n* Have pathologically confirmed diagnosis of unresectable or metastatic triple negative breast cancer (TNBC) with no curative treatment options\n* No chemotherapy, radiotherapy, or major surgery within 4 weeks of protocol treatment\n* Checkpoint inhibitor refractory patients (i.e., no longer responding to chemotherapy and checkpoint inhibitor) who have disease progression on prior line of chemotherapy and pembrolizumab, and, who in the opinion of the physician, can continue checkpoint inhibitor\n* Patients must be agreeable to pre- and 6-week post treatment biopsy in part 1 of the study\n\n  * The pre-treatment biopsy for this study must be taken at least 4 weeks after all previous chemotherapy (pembrolizumab is allowed during this period)\n* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately\n* Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =\\\u003C 1\n* Platelets \\>= 100,000\u002FuL\n* Hemoglobin \\>= 9.0 g\u002FdL\n* Absolute neutrophil count (ANC) \\>= 1500\u002FuL\n* Total bilirubin =\\\u003C institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 X institutional ULN\n* Creatinine clearance \\>= 50 mL\u002Fmin per Cockcroft-Gault equation\n* HbA1C \\\u003C=8.5\n* Have measurable disease per RECIST 1.1 criteria present\n* Ability to swallow and retain oral medication\n* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee\u002FInstitutional Review Board approved written informed consent form prior to receiving any study related procedure\n\nExclusion Criteria:\n\n* Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment\n* Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation\n* Patients with rapidly progressive disease\u002F symptomatic disease\n* Patients with primary resistance (i.e., did not respond to initial treatment with chemotherapy plus checkpoint inhibitor) with progressive disease at 12 weeks after starting chemotherapy and pembrolizumab\n* Patients who are pregnant or nursing. Women of childbearing potential (WOCBP) will have to undergo a urine pregnancy test as part of screening\n* Participants with symptomatic known brain metastases \\\u003C 4 weeks from radiation treatment should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events\n* History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastases or death\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Unwilling or unable to follow protocol requirements\n* Contraindications to the use of beta-blockers, like: uncontrolled depression, unstable angina pectoris, uncontrolled heart failure (grade III or IV), hypotension (systolic blood pressure \\\u003C 100 mmHg), severe asthma or chronic obstructive pulmonary disease (COPD), uncontrolled type I or type II diabetes mellitus (hemoglobin A1C \\[HbA1C\\] \\> 8.5 or fasting plasma glucose \\> 160 mg\u002Fdl at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, current use of beta-blockers or non-dihydropyridine calcium channel blockers\n* Any additional condition which in the investigator's opinion deems the participant an unsuitable candidate to receive the study drugs","FEMALE",{"count":248,"type":20},37,[23],"This phase II trial tests how well propranolol and pembrolizumab work to cause tumor re-sensitization and therefore treatment in patients with triple negative breast cancer that has not responded to previous checkpoint inhibitor therapy (refractory), cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). Propranolol is a drug that is classified as a beta-blocker. Beta-blockers affect the heart and circulation. Beta-blockers, like propranolol, may help to counteract effects of certain stress hormones produced by the body during cancer treatment and may increase the effectiveness of the pembrolizumab. Pembrolizumab is a drug that is classified as an immune checkpoint inhibitor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Propranolol may be able to re-sensitize the cells of the immune system to respond to the checkpoint inhibitor pembrolizumab in patients with checkpoint inhibitor refractory metastatic or unresectable triple negative breast cancer.",[55,26,28,252,67],"Refractory Triple-Negative Breast Carcinoma","2026-06-03",{"date":255,"type":33},"2026-06-04",{"date":257,"type":33},"2024-09-01",{"date":259,"type":20},"2029-06-30",{"name":261,"class":97},"Emory University",{"id":263,"slug":264,"hasResults":11,"nctId":265,"briefTitle":266,"officialTitle":267,"acronym":4,"eligibilityCriteria":268,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":269,"targetDuration":4,"studyType":21,"phases":270,"briefSummary":271,"conditions":272,"keywords":279,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":293,"lastUpdatePostDateStruct":294,"startDateStruct":296,"completionDateStruct":298,"leadSponsor":300,"locationsCount":301},"100535064","phase-1-a-study-of-pembrolizumab-and-cryoablation-in-people-with-breast-cancer-100535064","NCT06246968","A Study of Pembrolizumab and Cryoablation in People With Breast Cancer","Does Cryoablation Boost Immune Response Improving the Benefits of Pembrolizumab in Patients With Metastatic or Locally Advanced Triple Negative Breast Cancer?","Inclusion Criteria:\n\n* Patients ≥ 18 years of age\n* Confirmed histologic diagnosis of metastatic TNBC\n* 1 site amenable cryoablation of at least 1.5 cm in size as determined by an Interventional Radiologist. Eligible cryoablation sites include (but not limited to) soft tissue, liver, lung, and bone as determined by an Interventional Radiologist to be safest and most feasible.\n* Physically fit (clinically eligible) to undergo cryoablation as per usual clinical practice\n* Per clinical guidelines, women of childbearing age should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of the drug, which will be assessed and monitored by, and the responsibility of, the patient's medical oncologist (not study investigators or research team) as pembrolizumab is standard of care. Memorial Sloan Kettering Cancer Center Pregnancy Standards will be followed prior to cryoablation. That is, female patients that are 11-50 years of age and of childbearing potential will undergo a pregnancy test within 2 weeks (15 days) before cryoablation. Pregnancy test will not be required in patients with bilateral oophorectomy, bilateral salpingectomy, bilateral salpingectomy-oophorectomy, hysterectomy, menopause (no menses ≥ 1 year prior to treatment or after completion of all treatment), or surgical sterilization (i.e. tubal ligation or blockage), with documentation of permanent exemptions in CIS (\"Pregnancy Testing Exemption\").\n* Pembrolizumab therapy (200 mg every 3 weeks) planned as part of standard of care as first, second, or third line of therapy\n\n  * Eligible for PD-1 inhibitor per the patient's medical oncologist, with planned treatment with PD-1 inhibitor per the patient's medical oncologist. Additional systemic therapy is per the patient's medical oncologist. The following systemic therapy will be accepted (the timing of the systemic therapy relative to pembrolizumab and cryoablation is not restricted):\n\n    * Capecitabine (Xeloda, available as a generic drug)\n    * Carboplatin (Paraplatin, available as a generic drug)\n    * Cisplatin (Platinol, available as a generic drug)\n    * Cyclophosphamide (Cytoxan, available as a generic drug)\n    * Docetaxel (Taxotere)\n    * Doxorubicin (Adriamycin, available as a generic drug)\n    * Pegylated liposomal doxorubicin (Doxil)\n    * Epirubicin (Ellence, available as a generic drug)\n    * Eribulin (Halaven)\n    * Fluorouracil (5-FU, Adrucil, available as a generic drug)\n    * Gemcitabine (Gemzar, available as a generic drug)\n    * Ixabepilone (Ixempra)\n    * Methotrexate (available as a general drug)\n    * Nab-paclitaxel (Abraxane)\n    * Paclitaxel (Taxol, available as a generic drug)\n    * Vinorelbine (Navelbine, available as a generic drug)\n\nExclusion Criteria:\n\n* Patient not eligible for PD-1 inhibitor per the patient's medical oncologist\n* No disease amenable for cryoablation\n* Pembrolizumab therapy not planned as part of standard of care",{"count":41,"type":20},[52],"Participants will have a confirmed diagnosis of metastatic breast cancer and will receive pembrolizumab in combination with cryoablation OR pembrolizumab alone. Participants will be randomly assigned.",[273,274,275,276,277,28,278,140],"Metastatic Breast Cancer","Breast Cancer","Breast Cancer Stage IV","Triple Negative Breast Cancer","Triple Negative Breast Neoplasms","Locally Advanced Breast Cancer",[280,281,282,283,284,285,286,287,288,289,290,291,292],"metastatic TNBC","metastatic triple negative breast carcinoma","metastatic breast cancer","breast cancer","breast cancer stage IV","triple negative breast cancer","pembrolizumab","cryoablation","Memorial Sloan Kettering Cancer Center","23-390","locally advanced breast cancer","locally advanced triple negative breast carcinoma","locally advanced triple negative breast cancer","2026-05-18",{"date":295,"type":33},"2026-05-20",{"date":297,"type":33},"2024-01-29",{"date":299,"type":20},"2027-01-29",{"name":288,"class":97},7,{"id":303,"slug":304,"hasResults":11,"nctId":305,"briefTitle":306,"officialTitle":307,"acronym":4,"eligibilityCriteria":308,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":309,"targetDuration":4,"studyType":21,"phases":311,"briefSummary":312,"conditions":313,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":314,"lastUpdatePostDateStruct":315,"startDateStruct":317,"completionDateStruct":319,"leadSponsor":321,"locationsCount":322},"100471739","phase-1-testing-the-addition-of-anti-cancer-drug-zen003694-zen-3694-and-pd-1-inhibitor-pembrolizumab-to-standard-chemotherapy-nab-paclitaxel-treatment-in-patients-with-advanced-triple-negative-breast-cancer-100471739","NCT05422794","Testing the Addition of Anti-Cancer Drug, ZEN003694 (ZEN-3694) and PD-1 Inhibitor (Pembrolizumab), to Standard Chemotherapy (Nab-Paclitaxel) Treatment in Patients With Advanced Triple-Negative Breast Cancer","A Phase 1b Trial of ZEN003694 (ZEN-3694) With Pembrolizumab and Nab-Paclitaxel in Patients With Metastatic Triple-Negative Breast Cancer","Inclusion Criteria:\n\n* Participants must have a histologically or cytologically confirmed diagnosis of TNBC based on standard criteria for the disease:\n\n  * Estrogen receptor (ER) and progesterone receptor (PR) \\\u003C 10% by immunohistochemistry (IHC), and HER2-negative (per current American Society of Clinical Oncology \\[ASCO\\]\u002FCollege of American Pathologists \\[CAP\\] guidelines)\n  * If there is more than one histological result available, the most recent sample with ER, PR and HER2 results will be considered for inclusion\n  * Patients who have not had ER, PR and HER2 testing and thus, ER, PR and HER2 status is unknown, are not eligible\n  * Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation\n* Participants must have disease that is unresectable locally advanced or metastatic\n* DOSE ESCALATION COHORT: Known PD-L1 status is not required prior to study enrollment. Central PD-L1 testing (on archival tumor tissue) will occur retrospectively\n* DOSE ESCALATION COHORT: Any number of prior lines of therapy are allowed in the metastatic setting. Prior immune checkpoint inhibitor allowed in any setting\n* DOSE ESCALATION COHORT: Evaluable or measurable disease per RECIST 1.1 criteria\n* DOSE EXPANSION COHORT: PD-L1 status must be negative. Standard local testing with any PD-L1 antibody that has been validated in a Clinical Laboratory Improvement Act (CLIA)- certified environment will be acceptable for including patients on trial. Primary or metastatic samples may be tested for PD-L1 status. Central confirmation will occur retrospectively. For patients in whom a baseline research tumor tissue biopsy is not performed (e.g. site of disease is not safely accessible), archival tissue should be provided for central confirmatory PD-L1 testing\n* DOSE EXPANSION COHORT: 0-1 prior lines of systemic therapy in the metastatic setting\n* DOSE EXPANSION COHORT: Participants must have measurable disease per RECIST 1.1 criteria\n* DOSE EXPANSION COHORT: Participants must have disease that is amenable to biopsy as judged by the treating investigator and must be willing to undergo pre- and on-treatment tumor biopsies, if safely accessible\n* Age \\>= 18 years\n\n  * Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with nab-paclitaxel and pembrolizumab (MK-3475) in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 (Karnofsky \\>= 60%)\n* Absolute neutrophil count \\>= 1,000\u002FmcL\n* Platelets \\>= 100,000\u002FmcL\n* Hemoglobin \\>= 9 g\u002FdL or \\>= 5.6 mmol\u002FL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) (or =\\\u003C 2.0 x ULN in patients with documented Gilbert's Syndrome)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) \u002F alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 3.0 x institutional ULN or ≤ 5.0 x institutional ULN for participants with documented liver metastases\n* Serum or plasma creatinine =\\\u003C 1.5 x institutional ULN OR glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin (based on the calculated chronic kidney disease epidemiology (CKD-EPI) glomerular filtration rate estimation\n* International normalized ratio (INR) or prothrombin time (PT): =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants\n* Activated partial thromboplastin time (aPTT): =\\\u003C 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial as long as their anti-retroviral therapy does not have the potential for drug-drug interactions as judged by the treating investigator\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with history of treated central nervous system (CNS) metastases are eligible, provided they meet the following criteria:\n\n  * Disease outside the CNS is present\n  * Recovery from acute toxicity associated with the treatment to =\\\u003C Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 or baseline (with the exception of alopecia), with no requirement for escalating doses of corticosteroids over the past 7 days\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer are allowed\n* Patients should be New York Heart Association Functional Classification of class 2B or better\n* Peripheral neuropathy grade =\\\u003C 1\n* Ability to swallow and retain oral medications\n* Participants may not have had cytotoxic chemotherapy, immunotherapy, major surgery (other than diagnostic surgery, dental surgery or stenting), or other investigational therapy within 3 weeks prior to entering the study\n* Participants may not have had radiotherapy within 1 week prior to entering the study. Patients may not have had \\> 25% of their bone marrow radiated. Stereotactic radiosurgery (SRS) within 1 week prior to entering the study will be allowed\n* Participants may not have received tyrosine kinase inhibitors (TKIs) or small molecules within 5 half-lives or 2 weeks (whichever is shorter) of study entry\n* Patients who have experienced adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) must have recovered, with the exception of alopecia or as otherwise specified in the eligibility criteria\n* The effects of the combination of ZEN003694 (ZEN-3694) and MK-3475 on the developing human fetus are unknown. For this reason and because BETi and PD-1 blocking agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after study completion. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694), MK-3475 and nab-Paclitaxel administration. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to registration. Childbearing potential is defined as: participants who have not reached a postmenopausal state (\\>= 12 continuous months of amenorrhea with no identified cause other than menopause) and have not undergone surgical sterilization (removal of ovaries and\u002For uterus)\n* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and\u002For family member available will also be eligible\n\nExclusion Criteria:\n\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694), nab-paclitaxel, or pembrolizumab\n* Patients with uncontrolled intercurrent illness\n* Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment\n* Any gastrointestinal (GI) disorder that may affect absorption of oral medications in the opinion of the treating investigator, such as malabsorption syndrome or major bowel or stomach resection\n* Pregnant women are excluded from this study because ZEN003694 (a BETi agent) and MK-3475 have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued if the mother is treated with ZEN003694 (ZEN-3694). These potential risks may also apply to MK-3475 and nab-paclitaxel\n* Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor\n* DOSE EXPANSION COHORT: Prior exposure to immune checkpoint inhibitors in the metastatic setting. PD-1 or PD-L1 inhibitors in the neo-\u002Fadjuvant setting are allowed if at least 12 months have elapsed since the end of adjuvant systemic treatment to development of metastatic disease\n* DOSE EXPANSION COHORT: Prior exposure to taxane-based therapy in the metastatic setting. Taxane in the neo-\u002Fadjuvant setting is allowed if at least 12 months have elapsed since the end of adjuvant systemic treatment to development of metastatic disease\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 (ZEN-3694). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients receiving any medications or substances that are Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed\n* Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694 (ZEN-3694)\n* Myocardial infarction or unstable angina within 6 months prior to the first dose of ZEN003694 (ZEN-3694)\n* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)\n* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis\n* Has a known history of active tuberculosis (TB)\n* Has received a live vaccine within 30 days of planned treatment start. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster, yellow fever, rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine. Seasonal flu vaccines that do not contain live virus are permitted. Coronavirus disease-2019 (COVID-19) vaccines received within the last 30 days are also permitted\n* Participants with known or suspected extensive bone marrow infiltration per radiographic assessment, laboratory assessment, or bone marrow sampling (e.g., aspiration or biopsy), determined to be clinically significant by the treating investigator",{"count":310,"type":20},57,[52],"This phase Ib trial tests the safety and tolerability of ZEN003694 in combination with an immunotherapy drug called pembrolizumab and the usual chemotherapy approach with nab-paclitaxel for the treatment of patients with triple negative-negative breast cancer that has spread to other parts of the body (advanced). Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Immunotherapy with monoclonal antibodies, such as pembrolizumab may help the body's immune system attach the cancer and may interfere with the ability of tumor cells to grow and spread. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Combination therapy with ZEN003694 pembrolizumab immunotherapy and nab-paclitaxel chemotherapy may help shrink or stabilize cancer for longer than chemotherapy alone.",[55,26,140,28,67],"2026-05-12",{"date":316,"type":33},"2026-05-13",{"date":318,"type":33},"2023-05-18",{"date":320,"type":20},"2027-03-31",{"name":39,"class":40},6,{"id":324,"slug":325,"hasResults":11,"nctId":326,"briefTitle":327,"officialTitle":328,"acronym":4,"eligibilityCriteria":329,"healthyVolunteers":11,"sex":246,"minAge":17,"maxAge":4,"enrollmentInfo":330,"targetDuration":4,"studyType":21,"phases":332,"briefSummary":333,"conditions":334,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":337,"lastUpdatePostDateStruct":338,"startDateStruct":340,"completionDateStruct":342,"leadSponsor":344,"locationsCount":346},"100389274","phase-2-dendritic-cell-vaccines-against-her2her3-and-pembrolizumab-for-the-treatment-of-brain-metastasis-from-triple-negative-breast-cancer-or-her2-breast-cancer-100389274","NCT04348747","Dendritic Cell Vaccines Against Her2\u002FHer3 and Pembrolizumab for the Treatment of Brain Metastasis From Triple Negative Breast Cancer or HER2+ Breast Cancer","A Phase IIa Study of Dendritic Cell Vaccines Against Her2\u002FHer3 and Pembrolizumab in Patients With Asymptomatic Brain Metastasis From Triple Negative Breast Cancer (TNBC) or HER2+ Breast Cancer (HER2+BC) or Hormone Receptor Positive (HR+) Breast Cancer.","Inclusion Criteria:\n\n* female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least one of the following conditions applies:\n\n  * Not a woman of childbearing potential (WOCBP)\n  * A WOCBP who agrees to follow contraceptive guidance\n* WOCBP must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood:this may be a period of several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used. NOTE: If the risk of conception exists, patients must agree to use highly effective contraception throughout the study and for at least two years following the last study treatment administration\n* Negative serum and highly sensitive urine pregnancy test(s):\n* At initial screening prior to eligibility confirmation\n* within 72 hours prior to leukapheresis if \\>72 hours have passed between screening test and the Leukapheresis visit\n* Pregnancy testing will be performed for WOCBP and interpreted prior to every cycle of pembrolizumab (Initial Treatment Phase);\n* at the End of Treatment (EOT) Assessment; and\n* whenever pregnancy is otherwise suspected. Note: In the event that 72 hours have elapsed between the screening pregnancy test and leukapheresis, another pregnancy test must be performed and must be negative in order for subject to undergo leukapheresis\n* Histologically or cytologically confirmed diagnosis of triple negative breast cancer (TNBC) (estrogen receptor \\[ER\\] =\\\u003C 1%, progesterone receptor \\[PR\\] =\\\u003C 1% HER2 negative) or HR+ breast cancer\n\n  * HER2 testing should be performed on the invasive component using a validated immunohistochemistry (IHC) or in situ hybridization (ISH) assay\n  * IHC staining is defined as:\n\n    * IHC 3+ if there is complete and intense circumferential membrane staining within \\> 10 percent of tumor cells. All IHC 3+ tumors are considered HER2 positive\n    * IHC 2+ if there is incomplete and\u002For weak\u002Fmoderate, circumferential membrane staining within \\> 10 percent of tumor cells. All IHC 2+ tumors are reported as HER2 equivocal\n    * IHC 1+ if there is faint or barely perceptible, incomplete membrane staining within \\> 10 percent of tumor cells. All IHC 1+ tumors are reported as HER2 negative\n    * IHC 0 if (1) no staining is observed, or (2) there is faint or barely perceptible, incomplete membrane staining within \\\u003C 10 percent of tumor cells. All IHC 0 tumors are reported as HER2 negative\n    * Equivocal HER2 testing should trigger reflex HER2 testing using ISH on the same specimen or a new test (using a different specimen with either IHC or ISH)\n  * Results from ISH are defined as the ratio of gene amplification of HER2 and the chromosome 17 enumeration probe (CEP17). Results are reported as:\n\n    * ISH positive if the HER2\u002FCEP17 ratio is \\>= 2.0, and the HER2 copy number signals\u002Fcell is \\>= 4\n    * Definitive diagnosis will be rendered pending further workup in the following instances:\n\n      * If the HER2\u002FCEP17 ratio is \\>= 2.0 and an average HER2 copy number is \\\u003C 4.0 signals\u002Fcell - negative if confirmed on retesting\n      * If the HER2\u002FCEP17 ratio is \\\u003C 2.0 and the average HER2 copy number is \\>= 6.0 signals\u002Fcell positive - if confirmed on retesting\n      * If the HER2\u002FCEP17 ratio is \\\u003C 2.0 and an average HER2 copy number is between \\>= 4.0 and \\\u003C 6.0 signals\u002Fcell negative - if confirmed on retesting\n    * ISH negative if the HER2\u002FCEP17 ratio is \\\u003C 2.0 and average HER2 copy number is \\\u003C 4.0 signals\u002Fcell\n* Measurable brain disease as per RANO-BM criteria modified to include the cut off point of 0.5 cm or higher. Have at least one untreated (includes irradiation) brain metastasis approved by a research team that meets the following size requirements:\n\n  * \\>= 0.5 cm AND twice the magnetic resonance imaging (MRI) slice thickness; and\n  * \\\u003C 3.0 cm, that is asymptomatic and does not require local therapy at the time of enrollment (i.e. target lesion\\[s\\])\n  * Of note, lesions \\>= 0.5 cm and \\\u003C 3 cm may be determined ineligible by the research team because of location or symptoms. An untreated brain metastasis is defined as a lesion not present at the time of whole brain radiation therapy or not included in a stereotactic radiotherapy field (or within 0.5 cm of a treated lesion), or any lesion that is new or unequivocally progressing since prior radiation therapy or prior surgery.\n* Any brain metastasis \\>= 3.0 cm or causing symptoms must have previously been treated with local therapy (i.e. radiation or surgical resection, as clinically appropriate) prior to study enrollment. Any lesion present at the time of whole brain radiation therapy (WBRT) or included in the stereotactic radiotherapy field (or within 5 mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment\n* Stereotactic radiosurgery (SRS) and\u002For prior radiotherapy is permitted \\>=2 weeks prior to initial Dendritic Cell (DC) vaccine dose (leaving one or more lesions which are not radiated and will be used as target lesions) but a follow up brain MRI should be obtained prior to dendritic cell (DC) vaccine to determine stability of the lesions. An interval of at least 4 weeks after the end of whole brain radiation or for any surgical resection of brain lesions is permitted ; an interval of at least 4 weeks or 5 half-lives (whichever is sorter) after the last cytotoxic, targeted, immunotherapeutic or investigational agent is permitted (prior to the start of DC vaccine)\n\n  * Previous whole brain radiation is allowed if patient has been diagnosed with recurrent, progressive brain metastasis. Previously irradiated lesions would be considered non-target lesions\n  * Previously resected lesions or those treated with SRS would be considered nontarget lesions. There is no limitation on prior local therapies to other lesions.\n* If subject received major surgery, they must have recovered adequately from the toxicity and\u002For complications from the intervention prior to starting therapy\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Toxicity that has not recovered to \\\u003C=Grade 1 is allowed if it meets the inclusion requirments for lab parameters (Participants with \\\u003C= Grade 2 neuropathy may be eligible)\n* Patients must have adequate organ and marrow function as defined below (specimens must be collected within 10 days prior to the start of study treatment):\n* Hemoglobin \\>= 9 g\u002FdL or \\>= 5.6 mmol\u002FL\n* Leukocytes: \\>= 3 x 10\\^9\u002FL\n* Absolute neutrophil count: \\>= 1.5 x 10\\^9\u002FL\n* Platelets: \\>= 100 x 10\\^9\u002FL\n* Total bilirubin: =\\\u003C 1.5 x upper limit of normal (ULN) OR direct bilirubin =\\\u003C ULN for participants with total bilirubin levels \\> 1.5 x ULN\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]): =\\\u003C 2.5 x institutional upper limit of normal (=\\\u003C 5 x ULN for participants with liver metastases)\n* Creatinine OR Measured or calculated creatinine clearance (Glomerular Filtration Rate (GFR) can also be used in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL\u002Fmin for participant with creatinine levels \\>1.5 × institutional ULN\n* International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (APTT) =\\\u003C 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants\n* No evidence of leptomeningeal disease\n* If patient is on steroids, they must be on a steroid dose less than or = to an equivalent prednisone dose of 10 mg daily\n* Life expectancy of \\> 3 months\n* Prior checkpoint inhibitors permitted 3 weeks prior to enrollment\n* If the disease has progressed on current treatment in the CNS, prior to consent, patients may continue Her 2 directed antibody treatment (trastuzumab and pertuzumab); aromatase inhibitor or tamoxifen while on the study; patients with triple negative breast cancer may continue capecitabine, eribulin or paclitaxel while on study per PI discretion\n* Patients with systemic disease will be managed as detailed in Section 10.1 - Patients who develop systemic disease progression on the protocol will be managed as detailed in Section 10.4.2\n\nExclusion Criteria:\n\n* Any condition which might confound the results of the study, interfere with the subject's participation for full participation (for the full duration of the study) or in the Investigator's opinion deems the participant an unsuitable candidate for the study\n* Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drugs\n* May not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of DC vaccine treatment\n* Has had prior chemotherapy or targeted small molecule therapy (except treatment mentioned in inclusion criteria 17) within 4 weeks or 5 half-lives (whichever is sooner) prior to start of treatment (first DC vaccine) or who has not recovered (i.e., =\\\u003C grade 1 or at baseline) from adverse events due to a previously administered agent. Previous radiation to extracranial sites may be completed at any time prior to initiation of study drugs (first DC vaccine) with a 2-week washout is required.\n* Rapidly progressing systemic disease which might interfere with completion of all the vaccine doses\n* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed\n* History of allogenic tissue\u002Fsolid organ transplantation\n* Has an active infection requiring systemic therapy which in the investigator's opinion will increase risk to the patient\n* Has known active hepatitis B or hepatitis C infection (Testing is not mandatory)\n* Has known immunosuppressive disease (e.g. human immunodeficiency virus \\[HIV\\], acquired immunodeficiency syndrome \\[AIDS\\] or other immune depressing disease). Testing is not mandatory\n* Has received a blood transfusion in the two weeks prior to leukapheresis\n* Pregnant or actively nursing (females who agree to stop nursing would be eligible) participants\n* Unwilling or unable to follow protocol requirements\n* Brain lesion size with significant midline shift or obstructive hydrocephalus\n* The use of corticosteroids to control cerebral edema or treat neurologic symptoms will not be allowed unless at a low dose, not to exceed 10 mg of prednisone (or equivalent) per day\n* History of stroke or transient ischemic attack within 6 months prior to study enrollment\n* History of (non-infectious) pneumonitis \u002Finterstitial lung disease that required steroids, or has current pneumonitis\u002F interstitial lung disease\n* Presence of leptomeningeal disease\n* Any contraindication to MRI (i.e., patients with pacemakers or other metal implanted medical devices). An MRI safety questionnaire is required prior to MR imaging\n* Has received prior radiotherapy within 2 weeks of start of study treatment with dendritic cell (DC) vaccine and\u002For has received SRS \\\u003C2. weeks prior to the administration of the first DC vaccine dose. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\\\u003C 2 weeks of radiotherapy) to non-CNS disease\n* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Seasonal influenza vaccines for injection are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. Administration of killed vaccines is allowed.\n* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug (DC vaccine)\n* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded\n* A WOCBP who has a positive urine or blood pregnancy test at screening and within 72 hrs prior to leukapheresis\n\n  \\*Note: in the event that 72 hrs have elapsed between the initial screening pregnancy test and leukapheresis, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to undergo leukapheresis\n* Known active carcinomatous meningitis\n* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.",{"count":331,"type":20},23,[23],"This phase IIa trial studies how well dendritic cell vaccines against Her2\u002FHer3 and pembrolizumab work for the treatment of triple negative breast cancer or HER2+ breast cancer or HER+ Breast cancer that has spread to the brain (brain metastasis). Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the cancer cells. . Pembrolizumab is an \"immune checkpoint inhibitor\" which is designed to either \"unleash\" or \"enhance\" the cancer immune responses that already exist by either blocking inhibitory molecules\" or by activating stimulatory molecules. Giving dendritic cell vaccines and pembrolizumab may shrink the cancer.",[26,335,28,336],"Metastatic Malignant Neoplasm in the Brain","Prognostic Stage IV Breast Cancer AJCC v8","2026-05-07",{"date":339,"type":33},"2026-05-11",{"date":341,"type":33},"2022-12-19",{"date":343,"type":20},"2027-12-15",{"name":345,"class":97},"Roswell Park Cancer Institute",3,{"id":348,"slug":349,"hasResults":11,"nctId":350,"briefTitle":351,"officialTitle":352,"acronym":4,"eligibilityCriteria":353,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":354,"targetDuration":4,"studyType":21,"phases":356,"briefSummary":357,"conditions":358,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":359,"lastUpdatePostDateStruct":360,"startDateStruct":362,"completionDateStruct":364,"leadSponsor":366,"locationsCount":98},"100463728","phase-1-ivermectin-in-combination-with-balstilimab-or-pembrolizumab-in-patients-with-metastatic-triple-negative-breast-cancer-100463728","NCT05318469","Ivermectin in Combination With Balstilimab or Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer","A Phase I\u002FII Study Evaluating the Safety and Efficacy of Ivermectin in Combination With Immune Checkpoint Inhibitor in Patients With Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Age: ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) ≤ 1\n* Life expectancy \\> 3 months\n* Histologically confirmed metastatic triple negative breast cancer. Triple negative status will be defined as estrogen receptor (ER) and progesterone receptor (PR) ≤ 10% and HER2 negative (by immunohistochemistry \\[IHC\\] or fluorescence in situ hybridization \\[FISH\\]), per American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines\n* Patients must have progressed on 1-2 prior lines of systemic therapy (chemotherapy and\u002For drug-antibody conjugate) in the metastatic setting\n* Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 2 from prior anti-cancer therapy\n* For Phase 2 expansion only, must be PD-L1 negative. Note: For Phase 1 safety cohort, any PD-L1 status will be allowed to enroll.\n* Patients must have adequate organ function as defined in the following:\n* Absolute neutrophil count (ANC) ≥ 1,500\u002Fmm\\^3\n* Platelets ≥ 100,000\u002Fmm\\^3\n* Hemoglobin ≥ 9.0 g\u002FdL or ≥ 5.6 mmol\u002FL. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks\n* Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \\> 1.5 x ULN\n* Aspartate aminotransferase (AST) ≤ 1.5 x ULN or ≤ 3 x ULN with liver metastases\n* Alanine aminotransferase (ALT) ≤ 1.5 x ULN or ≤ 3 x ULN with liver metastases\n* Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 30 mL\u002Fmin for participant with creatinine levels \\>1.5 x institutional ULN\n* International normalized ratio (INR) or prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants\n* Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test\n\n  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period\n* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:\n\n  * Not a woman of childbearing potential (WOCBP) OR\n  * Females of child-bearing potential must be willing to use effective contraception during study and for 120 days after the last dose\n* Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.\n\nExclusion Criteria:\n\n* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug\n* Prohibited Treatments and\u002For Therapies:\n* Chemotherapy, radiation therapy, biological therapy, immunotherapy within 28 days prior to day 1 of protocol therapy\n* Prior immune checkpoint inhibitor therapy in metastatic setting (Note: Prior use of immune checkpoint inhibitor in neoadjuvant or adjuvant setting only permitted if last dose is at least 1 year from start of study intervention)\n* Prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease\n* Any live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed\n* Participants on any dose of warfarin. Use of low molecular weight heparin, antithrombin agents, anti-platelet agents or factor Xa inhibitors is allowed\n* Participants may not be currently participating in or participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention\n* Issues with tolerating oral medication (e.g., inability to swallow pills, malabsorption issues, ongoing nausea or vomiting during screening)\n* Women who are or are planning to become pregnant or breastfeed\n* Known allergy to any of the components within the study agents and\u002For their excipients\n* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years\n* Participants must not have known active CNS metastases and\u002For carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention\n* History of (non-infectious) pneumonitis that required steroids or has current pneumonitis\n* Active infection requiring systemic therapy\n* Known history of Human Immunodeficiency Virus (HIV) infection\n* Known history of Hepatitis B (defined as Hepatitis B surface antigen \\[HBsAg\\] reactive) or known active Hepatitis C virus (defined as HCV RNA \\[qualitative\\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority\n* Known history of active TB (Mycobacterium tuberculosis)\n* Intercurrent or historic medical condition that increases subject risk in the opinion of the Investigator. Eligibility may be revisited for intercurrent medical conditions once resolution\u002Frecovery is deemed adequate by the investigator (e.g., recovery from major surgery, completion of treatment for severe infection).\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment\n* Has had an allogenic tissue\u002Fsolid organ transplant\n* Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) class II, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at screening\n* Subjects having \\> 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \\\u003C 1 g\u002F24 hours\n* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed\n* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures",{"count":355,"type":20},34,[52,23],"This phase II trial studies the side effects and best dose of ivermectin in combination with balstilimab or pembrolizumab and to see how well they they work in shrinking tumors in patients with triple negative breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as balstilimab or pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivermectin may help block the formation of growths that may become cancer. Giving ivermectin with balstilimab or pembrolizumab may increase the effect of balstilimab or pembrolizumab in shrinking tumors in patients with triple negative breast cancer. The secondary objectives of the study include evaluating the following efficacy outcomes: objective response rate (ORR), progression free survival (PFS), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), and patients' quality of life (QOL) by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).",[26,28],"2026-05-01",{"date":361,"type":33},"2026-05-06",{"date":363,"type":33},"2023-10-13",{"date":365,"type":20},"2026-10",{"name":367,"class":97},"Yuan Yuan",{"id":369,"slug":370,"hasResults":11,"nctId":371,"briefTitle":372,"officialTitle":373,"acronym":4,"eligibilityCriteria":374,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":375,"targetDuration":4,"studyType":21,"phases":376,"briefSummary":377,"conditions":378,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":380,"lastUpdatePostDateStruct":381,"startDateStruct":383,"completionDateStruct":385,"leadSponsor":387,"locationsCount":98},"100549441","phase-2-tamoxifen-and-pegylated-liposomal-doxorubicin-for-the-treatment-of-patients-with-metastatic-or-inoperable-locally-advanced-triple-negative-breast-cancer-100549441","NCT06434064","Tamoxifen and Pegylated Liposomal Doxorubicin for the Treatment of Patients With Metastatic or Inoperable, Locally Advanced Triple Negative Breast Cancer","A Pilot, Single-Arm, Phase II Trial of Tamoxifen Plus Pegylated Liposomal Doxorubicin in Patients With Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Patients with pathologically confirmed metastatic triple negative breast cancer (ER ≤ 10%) that have been previously treated with at least 2 lines of therapy in the metastatic setting\n* Patients must have a confirmed eligible TP53 genomic alteration, as determined by the Roswell Park Oncomine™ Precision Assay (OPA) or similar CLIA-approved assay, using either an archival metastatic tumor sample or, if unavailable, a fresh biopsy. Uncertainty about the eligibility of the TP53 genomic alteration for this study can be resolved by discussion with the study PI\n* Patients must have ERα (estrogen receptor alpha) and PgR (progesterone receptor) status assessed using current American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines. Patients are eligible if the tumor staining is ERα low\u002Fnegative (ER ≤ 10%) and PgR negative by ASCO\u002FCAP guidelines\n* The tumor must be HER-2 negative by immunochemistry (IHC) 0-1+ or IHC 2 + and fluorescence in situ hybridization (FISH) negative\n* Patients must be ≥ 18 years of age\n* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n* Absolute neutrophil count (ANC) ≥ 1500\u002F μL\n* Hemoglobulin (hb) ≥ 9 g\u002FdL\n* Platelet count ≥ 100,000\u002F μL\n* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 x ULN\n* Creatinine clearance \\> 60 mL\u002Fmin (Cockroft-Gault Equation)\n* Left ventricular ejection fraction (LVEF) assessment must be performed within 30 days prior to enrollment. (LVEF assessment performed by 2-D echocardiogram is preferred; however, multigated acquisition scan \\[MUGA\\] scan may be substituted based on institutional preferences). The LVEF must be ≥ 50% regardless of the cardiac imaging facility's lower limit of normal\n* Patients must be able to swallow oral medications\n* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately\n* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee\u002FInstitutional Review Board approved written informed consent form prior to receiving any study related procedure\n\nExclusion Criteria:\n\n* Patients must not have any known contraindications to endocrine therapy, in the opinion of the treating investigator\n* Participants who have had chemotherapy, hormonal\u002Fendocrine therapy, immunotherapy, biologics or radiotherapy (as well as any other investigational agents\u002Fdevices) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin C), or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier\n* Have a known history of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to tamoxifen or any of its excipients\n* Patients known or suspected to have hypercoagulable syndrome or with history of venous or arterial thrombosis, stroke, transient ischemic attack (TIA), or pulmonary embolism\n* Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness\n* Cardiac disease (history of and\u002For active disease) that would preclude the use of the drugs included in the treatment regimen. This includes angina pectoris, arrhythmias except for benign premature ventricular contractions, a history of myocardial infarction, documented congestive heart failure (CHF) or cardiomyopathy\n* Patients with cirrhosis or severe hepatic impairment\n* Patients must not have a condition or an uncontrolled intercurrent illness including, but not limited to any of the following: ongoing or active infection requiring systemic treatment, except uncomplicated urinary tract infection (UTI), or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant or nursing female participants\n* Unwilling or unable to follow protocol requirements\n* Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug",{"count":41,"type":20},[23],"This phase II trial tests how well tamoxifen and pegylated liposomal doxorubicin works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or that has spread to nearby tissue or lymph nodes (locally advanced) and is unable to be operated on (inoperable). Tamoxifen works by blocking the effects of estrogen in the breast. This may help stop the growth of tumor cells that need estrogen to grow. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects and work better than other forms of the drug. Giving tamoxifen and pegylated liposomal doxorubicin together may work better in treating patients with metastatic or inoperable, locally advanced triple negative breast cancer than giving either of these drugs alone.",[55,26,379,28],"Locally Advanced Unresectable Triple-Negative Breast Carcinoma","2026-04-23",{"date":382,"type":33},"2026-04-24",{"date":384,"type":33},"2026-03-03",{"date":386,"type":20},"2028-11-30",{"name":345,"class":97},{"id":389,"slug":390,"hasResults":11,"nctId":391,"briefTitle":392,"officialTitle":393,"acronym":4,"eligibilityCriteria":394,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":395,"targetDuration":4,"studyType":21,"phases":397,"briefSummary":398,"conditions":399,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":400,"lastUpdatePostDateStruct":401,"startDateStruct":403,"completionDateStruct":405,"leadSponsor":407,"locationsCount":98},"100553951","phase-2-high-dose-radiation-therapy-with-pembrolizumab-and-chemotherapy-for-the-treatment-of-patients-with-pd-l1-positive-metastatic-triple-negative-breast-cancer-100553951","NCT06492759","High Dose Radiation Therapy With Pembrolizumab and Chemotherapy for the Treatment of Patients With PD-L1 Positive Metastatic Triple Negative Breast Cancer","A Phase II Study of High Dose Radiotherapy in Combination With Pembrolizumab Plus Chemotherapy in Patients With PD-L1 Positive Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Biopsy proven metastatic PD-L1 positive triple negative breast cancer with at least 2 sites of measurable metastatic disease on imaging\n\n  * Estrogen receptor (ER) and progesterone receptor (PR) negativity are defined as ≤ 10% of cells expressing hormonal receptors via immunohistochemistry (IHC) analysis\n  * HER2 negativity is defined as either of the following by local laboratory assessment\n\n    * In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 \\\u003C 2.0 or single probe average HER2 gene copy number \\\u003C 4 signals\u002Fcell) or\n    * IHC 0 or IHC 1+. If more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the Medical Monitor to establish eligibility of the patient\n* PD-L1 positive as defined by Dako 22c3 assay PD-L1 combined positive score (CPS) ≥ 10\n* Appropriate stage for study entry based on the following diagnostic workup:\n\n  * History and physical examination within 60 days prior to registration\n  * Clinical grade CT scans of the chest, abdomen, and pelvis with radionuclide bone scan or whole body positron emission tomography (PET)\u002FCT documenting metastatic disease within 4 weeks of the start of radiotherapy on this protocol with or without magnetic resonance imaging (MRI), as needed, documenting site of metastatic disease to be treated on protocol\n* Patient must be eligible for radiotherapy as determined by their treating physician\n* Patient must be eligible for immunotherapy and taxane chemotherapy as determined by their treating physician\n* At least 1 metastatic site amenable to high dose radiotherapy\n* Be willing and able to provide written informed consent for the trial\n* Ages ≥ 18 years of age\n* Biopsy proven metastatic PD-L1 positive triple negative breast cancer with at least 2 sites of measurable metastatic disease on imaging\n\n  * Estrogen receptor (ER) and progesterone receptor (PR) negativity are defined as ≤ 10% of cells expressing hormonal receptors via immunohistochemistry (IHC) analysis\n  * HER2 negativity is defined as either of the following by local laboratory assessment\n\n    * In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 \\\u003C 2.0 or single probe average HER2 gene copy number \\\u003C 4 signals\u002Fcell) or\n    * IHC 0 or IHC 1+. If more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the Medical Monitor to establish eligibility of the patient\n* PD-L1 positive as defined by Dako 22c3 assay PD-L1 combined positive score (CPS) ≥ 10\n* Appropriate stage for study entry based on the following diagnostic workup:\n\n  * History and physical examination within 60 days prior to registration\n  * Clinical grade CT scans of the chest, abdomen, and pelvis with radionuclide bone scan or whole body positron emission tomography (PET)\u002FCT documenting metastatic disease within 4 weeks of the start of radiotherapy on this protocol with or without magnetic resonance imaging (MRI), as needed, documenting site of metastatic disease to be treated on protocol\n* Patient must be eligible for radiotherapy as determined by their treating physician\n* Patient must be eligible for immunotherapy and taxane chemotherapy as determined by their treating physician\n* At least 1 metastatic site amenable to high dose radiotherapy\n* Be willing and able to provide written informed consent for the trial\n* Ages ≥ 18 years of age\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2, Karnofsky performance status (KPS) ≥ 60%\n* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1)\n* Absolute neutrophil count ≥ 1500\u002FmcL (obtained within 14 days prior to first study treatment)\n* Platelet count ≥ 100,000\u002FmcL (obtained within 14 days prior to first study treatment)\n* Hemoglobin ≥ 9.0 g\u002FdL (obtained within 14 days prior to first study treatment) (Note: The use of transfusion or other intervention to achieve hemoglobin \\[Hgb\\] ≥ 9.0g\u002FdL is acceptable)\n* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x the upper limit of normal (ULN) with the following exceptions (obtained within 14 days prior to first study treatment):\n\n  \\* Patients with documented liver metastases: AST and ALT ≤ 5 x ULN\n* Serum bilirubin ≤ 1.5 x ULN (obtained within 14 days prior to first study treatment)\n\n  \\* Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled\n* Calculated creatinine clearance ≥ 30 mL\u002Fmin (obtained within 14 days prior to first study treatment)\n* For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to radiation simulation\n* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry\n* Prior Treatment:\n\n  * Patients may or may not have received radiotherapy or neoadjuvant or adjuvant chemotherapy in the treatment of their initial, non-metastatic breast cancer, but must be entered on study after their last dose of radiotherapy, last cycle of chemotherapy and biologic therapy (if applicable) and have sufficient resolution of side effects per physician assessment at time of radiotherapy. Prior immunotherapy for treatment of early stage breast cancer is allowed if metastatic recurrence occurs ≥ 6 months after last dose of immunotherapy\n  * Patients must have not active wound healing issues from surgery and sufficient resolution of surgical side effects, per physician assessment, at time of radiotherapy\n  * Patients are not eligible if they have received chemotherapy in the advanced\u002Fmetastatic setting\n  * During radiotherapy, no other investigation or commercial agents or therapy for cancer other than bisphosphonate or receptor activator nuclear kappaB ligand (RANK-L) inhibitor, pembrolizumab, and nab-paclitaxel, paclitaxel, carboplatin or gemcitabine should be administered\n  * Patients may have received bisphosphonates or rank ligand inhibitors prior to enrollment on study\n\nExclusion Criteria:\n\n* Prior chemotherapy or targeted therapy for metastatic triple negative breast cancer before start of pembrolizumab plus partner chemotherapy. Prior chemotherapy (including taxanes) administered in the context of curative therapy (if treatment was completed \\> 6 months) prior to enrollment into the trial is allowed\n* Previous radiation to the metastases to be treated with radiation on this protocol\n* Untreated central nervous system (CNS) disease (patients with stable CNS disease for at least 28 days and asymptomatic treated CNS metastases are permitted)\n* Uncontrolled pleural effusion, pericardial effusion or ascites\n\n  \\* Patients with indwelling catheters (e.g., Pleurx) are allowed\n* Uncontrolled hypercalcemia (\\> 1.5 mmol\u002FL ionized calcium or calcium \\> 12 mg\u002FdL or corrected serum calcium \\> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab\n\n  \\* Patients who are receiving bisphosphonate therapy specifically to prevent skeletal prevents and who do not have a history of clinically significant hypercalcemia are eligible\n* History (Hx) of autoimmune disease that has required systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g.., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment\n* Use of chronic systemic glucocorticoid or immunosuppressive medications at time of enrollment (prednisone or equivalent steroid dose of \\> 10mg for \\> 2 weeks)\n* Prior allogeneic stem cell or solid organ transplantation\n* Severe, active co-morbidity such as congestive heart failure (CHF) or unstable angina within last 6 months, transmural myocardial infarction (MI) within the last 6 months\n* Acute bacterial or fungal infection requiring IV antibiotics at time of registration\n* History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan\n\n  \\* History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Chronic obstructive pulmonary disease (COPD) or other respiratory illness requiring hospitalization at time of registration\n* HIV positive with CD4 count \\\u003C 200 cells\u002F microliter\n* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy. Indolent cancers (such as low risk prostate or in-situ cancers) that are not being treated, are acceptable\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Examples include:\n\n  * Major surgical procedure within 28 days prior to randomization or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis\n  * Known hypersensitivity to nab-paclitaxel or to any of the excipients\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment",{"count":396,"type":20},29,[23],"This phase II trial tests how well radiation therapy with pembrolizumab and chemotherapy (paclitaxel or nab-paclitaxel or carboplatin and gemcitabine) works in treating patients with PD-L1 positive triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Carboplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. High dose radiation therapy with pembrolizumab and chemotherapy may effective in treating patients with PD-L1 positive metastatic triple negative breast cancer.",[26,28],"2026-04-14",{"date":402,"type":33},"2026-04-17",{"date":404,"type":33},"2025-10-22",{"date":406,"type":20},"2028-02-13",{"name":261,"class":97},{"id":409,"slug":410,"hasResults":11,"nctId":411,"briefTitle":412,"officialTitle":413,"acronym":4,"eligibilityCriteria":414,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":415,"targetDuration":4,"studyType":21,"phases":416,"briefSummary":417,"conditions":418,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":419,"lastUpdatePostDateStruct":420,"startDateStruct":422,"completionDateStruct":424,"leadSponsor":426,"locationsCount":98},"100598985","phase-2-a-cancer-vaccine-stemvac-in-combination-with-chemotherapy-for-the-treatment-of-pd-l1-negative-metastatic-triple-negative-breast-cancer-100598985","NCT07078604","A Cancer Vaccine (STEMVAC) in Combination With Chemotherapy for the Treatment of PD-L1 Negative Metastatic Triple-Negative Breast Cancer","A Phase II Trial of the Immunogenicity of a DNA Plasmid-Based Vaccine (STEMVAC) Encoding Th1 Selective Epitopes From Five Antigens Associated With Breast Cancer Stem Cells (MDM2, YB1, SOX2, CDH3, CD105) in Patients With Metastatic Triple-Negative Breast Cancer","Inclusion Criteria:\n\n* Patients must be at least ≥ 18 years of age\n\n  * Note: Because no dosing or adverse event (AE) data are currently available on the use of STEMVAC in patients \\\u003C 18 years of age, children and adolescents are excluded from this study, but will be eligible for future pediatric trials, if applicable\n* Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 2\n* Histologically confirmed triple-negative breast cancer\n\n  * Tumors with estrogen receptor (ER)-low (≤ 5%) or negative and progesterone receptor (PR)-low (≤ 5%) or negative will be included\n  * HER2-negative or HER2-low will be defined by the American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) 2023 \"Human Epidermal Growth Factor Receptor 2 (HER2) Breast Testing Guideline Update\" which reaffirms the 2018 \"HER2 Breast Testing Guideline Focused Update\"\n* Tumor is negative for PD-L1 marker testing per standard of care immunohistochemistry 22C3 pharmDx assay\n* Metastatic disease that is measurable based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment. This site should not be a site that is used to determine measurable disease for efficacy purposes. Lesions that will be biopsied should not be in a previously irradiated area unless progression has been demonstrated in such lesions\n* Patients should not have received any prior cancer immunotherapy in the metastatic setting\n* Prior Food and Drug Administration (FDA)-approved antibody drug conjugates are allowed\n* Patients are appropriate candidates to receive standard of care chemotherapy as per treating oncologist's clinical judgement\n* Patients who have received prior neoadjuvant or adjuvant chemotherapy are allowed\n* A minimum of 14 days washout since last systemic therapy or any palliative radiotherapy is required\n* Treatment with a bisphosphate or denosumab concurrently with protocol-specific therapy is allowed while on study (it is not exclusionary)\n* Patients must be at least 28 days post systemic steroids prior to enrollment, unless this is a steroid administered concurrently with chemotherapy or used as part of prophylaxis to prevent intravenous (IV) contrast reactions\n* Must have recovered from major infections and\u002For surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment\n* Willing to undergo up to two serial biopsies while on study\n* White blood cell (WBC) ≥ 2500\u002Fmm\\^3 (Within 28 days of receiving first study vaccine)\n* Lymphocyte count ≥ 500\u002Fmm\\^3 (Within 28 days of receiving first study vaccine)\n* Absolute neutrophil count (ANC) ≥ 1000\u002FμL (Within 28 days of receiving first study vaccine)\n* Hemoglobin (Hgb) ≥ 9 g\u002FdL (Within 28 days of receiving first study vaccine)\n* Platelets ≥ 75,000\u002FμL (Within 28 days of receiving first study vaccine)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be \\\u003C 3.0 mg\u002FdL (Within 28 days of receiving first study vaccine)\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (Within 28 days of receiving first study vaccine)\n* Creatinine ≤ 1.5 x ULN mg\u002FdL or creatinine clearance \\> 60 mL\u002Fmin (Within 28 days of receiving first study vaccine)\n* Patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a person of child-bearing potential. Acceptable methods of contraception are abstinence, condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. Effective methods of contraception must be used throughout the study until the end of treatment on study\n\nExclusion Criteria:\n\n* Patient has received more than one line of prior therapy in metastatic setting\n* Patients with tumors that are PD-L1-positive per standard of care immunohistochemistry 22C3 pharmDx assay\n* Enrollment in a concurrent interventional clinical trial. Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed\n* Patients with any of the following cardiac conditions:\n\n  * Symptomatic restrictive cardiomyopathy\n  * Dilated cardiomyopathy\n  * Unstable angina within 4 months prior to enrollment\n  * New York Heart Association functional class III-IV heart failure on active treatment\n  * Symptomatic pericardial effusion\n* Patients with any autoimmune disease or comorbidities that require chronic systemic steroids or immunosuppressants. Patients with conditions requiring inhaled, intranasal or topical steroids are permitted\n* Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF\n* A non-breast malignancy requiring radiation or systemic therapy within last 5 years or any B-cell malignancy (e.g., chronic lymphocytic leukemia or follicular lymphoma) under active surveillance\n* Pregnant and breastfeeding individuals\n* Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen \\[HBsAg\\] reactive), or hepatitis C (e.g., hepatitis C virus \\[HCV\\] ribonucleic acid \\[RNA\\] \\[qualitative\\] is detected)\n* Major surgery within the 4 weeks prior to initiation of study vaccine\n* Must be 14 days between a non-study vaccine, including live attenuated and non-live vaccines and any STEMVAC vaccination\n\n  * Note: The minimum of 14 days does not apply to the tetanus and diphtheria (Td) vaccine\n* Any condition that may interfere with the patient's participation in the study per treating physician",{"count":5,"type":20},[23],"This phase II trial studies how well a cancer vaccine called STEMVAC works in combination with chemotherapy in treating patients with PD-L1 negative, triple-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). STEMVAC is designed to target proteins that are expressed on breast cancer stem cells, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving STEMVAC in combination with chemotherapy may be an effective treatment for PD-L1 negative metastatic triple-negative breast cancer.",[26,28],"2026-04-01",{"date":421,"type":33},"2026-04-07",{"date":423,"type":33},"2026-03-20",{"date":425,"type":20},"2028-06-30",{"name":427,"class":97},"University of Washington",{"id":429,"slug":430,"hasResults":11,"nctId":431,"briefTitle":432,"officialTitle":433,"acronym":4,"eligibilityCriteria":434,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":435,"targetDuration":4,"studyType":21,"phases":437,"briefSummary":438,"conditions":439,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":458,"lastUpdatePostDateStruct":459,"startDateStruct":461,"completionDateStruct":463,"leadSponsor":465,"locationsCount":466},"100541006","phase-1-personalized-vaccine-immunotherapy-in-combination-with-checkpoint-inhibitor-for-treatment-of-triple-negative-breast-cancer-100541006","NCT06324240","Personalized Vaccine Immunotherapy in Combination With Checkpoint Inhibitor for Treatment of Triple Negative Breast Cancer","Clinical Evaluation of a Personalized Vaccine Immunotherapy in Combination With Checkpoint Inhibitor for Triple Negative Breast Cancer (TNBC)","Inclusion Criteria:\n\n* Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information\n* Must be age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days prior to tissue consent\n* Absolute neutrophil count \\> 1500\u002FmcL (obtained within 14 days prior to vaccine administration)\n* Absolute lymphocyte count \\>= 600 cells\u002Fµl (obtained within 14 days prior to vaccine administration)\n* Platelets \\> 100,000 mm (obtained within 14 days prior to vaccine administration)\n* Hemoglobin \\> 9.0 g\u002FdL (obtained within 14 days prior to vaccine administration) (NOTE: The use of transfusion or other intervention to achieve hemoglobin \\[Hgb\\] \\> 9.0g\u002Fdl is acceptable)\n* Serum creatinine =\\\u003C 1.5 x upper limit of normal (ULN) or calculated creatinine clearance \\>= 60 mL\u002Fmin using Cockcroft-Gault equation for patients with creatinine levels \\> 1.5 x institutional ULN (obtained within 14 days prior to vaccine administration)\n* Total bilirubin =\\\u003C 1.5 x ULN OR direct bilirubin =\\\u003C 1 x ULN (obtained within 14 days prior to vaccine administration)\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\\\u003C 2.5 x ULN unless liver metastases are present, in which case they must be =\\\u003C 5 x ULN (obtained within 14 days prior to vaccine administration)\n* Bilirubin =\\\u003C 1.5 X ULN (except in participants with documented Gilbert's disease, who must have a total bilirubin =\\\u003C 3.0 mg\u002FdL) (obtained within 14 days prior to vaccine administration)\n* International normalized ratio (INR) or prothrombin time (PT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (obtained within 14 days prior to vaccine administration)\n* Activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (obtained within 14 days prior to vaccine administration)\n* TNBC as defined by estrogen receptor (ER)\u002Fprogesterone receptor (PR) =\\\u003C 10% if Allred =\\\u003C 3; Her2\u002Fneu negative as defined by scores of 0 or 1+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of \\\u003C 2.0 or \\\u003C 6 Her2 copies per cell\n* Patients with metastatic or inoperable locally advanced disease: Metastatic or inoperable locally advanced disease is defined as either histologically confirmed metastatic breast cancer by biopsy; or locally advanced breast cancer that, in the opinion of the treating physician, is not amenable to curative intent surgical resection; or, radiological or clinical evidence suggestive and supportive of metastatic disease\n\n  * Documented metastatic biopsy is not required provided the patient has a prior diagnosis of TNBC that otherwise meets the eligibility criteria\n  * Eligible patients must have =\\\u003C 3 lines of chemotherapy in the metastatic\u002Fadvanced disease setting. For patients who have relapsed within 6 months of systemic therapy given within curative intent, that therapy will count as a line of metastatic therapy. Last cycle of cytotoxic therapy must be \\>= 21 days prior to cycle (C)1 day (D)1 of vaccine. Last cycle of checkpoint inhibitor therapy be \\>= 28 days prior to C1D1 of vaccine. Last dose of radiotherapy must be \\>= 14 days prior to C1D1 of vaccine\n  * Prior checkpoint inhibitor is permitted. Patients who are known to have PD-L1 positive with combined positive score (CPS) \\>= 10 will be required to have had pembrolizumab therapy prior to enrollment\n  * Patients who are metastatic or inoperable, locally advanced will only be eligible for the Phase 1b combination cohort. They will not be eligible for the Phase 1a dose escalation cohort. Patients who have received prior anti-CTLA-4 antibody will preferentially be enrolled to cohort B (combination of TMV vaccine with pembrolizumab). Patients who have received prior PD-L1 or PD-1 antibody therapy will preferentially be enrolled to cohort C (combination of TMV vaccine with ipilimumab). Patients with metastatic disease who have received no prior immune checkpoint inhibitor therapy will be assigned to a treatment arm based on available slots and discretion of treating physician\n* Patients with early stage TNBC: Early stage TNBC is defined as clinical or pathologic Stage I-III TNBC\n\n  * After resection of disease in the breast and axilla, early stage patients are eligible for either the Phase 1a dose escalation of TMV vaccine monotherapy Cohort A or the Phase 1b combination arm of the vaccine with immune checkpoint inhibitor (ICI)\n  * Patients will be required to have completed adjuvant radiotherapy (if indicated) \\>= 14 days prior to initiation of vaccine on trial\n  * Patients who have residual disease after completion neoadjuvant therapy that proceed with adjuvant capecitabine can enroll \\>= 28 days after completion of final dose of capecitabine. Patients electing to enroll onto the Phase 1a Cohort A monotherapy arm can enroll prior to initiation of capecitabine, however must not initiate capecitabine prior to the Week 12 blood draw (measurement of immune biomarkers) on study\n  * Patients who have a germline BRCA 1\u002F2 mutation that meet the Food and Drug Administration (FDA) indication for use of adjuvant Olaparib can enroll \\>= 28 days after completion of final dose of olaparib. Patients electing to enroll onto the Phase 1a Cohort A monotherapy arm can enroll prior to initiation of olaparib, however must not initiate olaparib prior to the Week 12 blood draw (measurement of immune biomarkers) on study\n  * Patients who undergo upfront surgery: Patients may initiate injection of vaccine \\>= 28 days after completion of final cycle of adjuvant chemotherapy\n  * Patients who have early stage breast cancer that have residual disease after completing neoadjuvant chemotherapy with the KEYNOTE 522 regimen (pembrolizumab at a dose of 200 mg every 3 weeks plus weekly paclitaxel and carboplatin for 4 cycles followed by pembrolizumab-doxorubicin-cyclophosphamide or of pembrolizumab-epirubicin-cyclophosphamide every 3 weeks for 4 cycles):\n\n    * Patient enrolling onto Phase 1a Cohort A will initiate injection of vaccine \\>= 28 days after completion of final cycle of standard of care adjuvant pembrolizumab\n    * Patient enrolling onto Phase 1b Cohort B or C will initiate injection of vaccine \\>= 28 days surgical resection. Patients who have received pembrolizumab as part of the preoperative KEYNOTE 522 regimen will preferentially be enrolled to cohort B (combination of TMV vaccine with pembrolizumab) and will receive up to 9 cycles of adjuvant pembrolizumab every 3 weeks as per standard of care. Vaccine will be administered every 2 weeks for 3 doses prior to the first three ICI cycles\n  * Patients who have early stage breast cancer that have that have residual disease after completing neoadjuvant chemotherapy with either dose-dense doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel-cyclophosphamide:\n\n    * Patient enrolling onto Phase 1a Cohort A will initiate injection of vaccine \\>= 28 days surgical resection\n    * Patient enrolling onto Phase 1b Cohort B or C will initiate injection of vaccine \\>= 28 days surgical resection. Patients will be assigned to receive either pembrolizumab (Cohort B) every 3 weeks for 6 cycles or ipilimumab (Cohort C) every 3 weeks for 4 cycles in combination with TMV vaccine based on available slots in each arm and discretion of treating physician. Vaccine will be administered every 2 weeks for 3 doses; the TMV vaccine will be administered prior to the ICI cycle if ICI is due.\n* Weight of tumor tissue for production of vaccine must be at least 1 gram. In metastatic patients, preferentially, invasive tumor in breast or lymph node tissue will be retrieved by excisional biopsy to ensure sufficient yield. In metastatic patients who undergo initiation of first-line standard of care systemic therapy off study (i.e. pembrolizumab and chemotherapy in a PD-L1 positive patient), then ideally collection of tumor tissue will occur prior to treatment initiation of standard of care therapy to maximize cellularity. Metastatic patients who have undergone mastectomy during curative treatment initially or have no invasive disease in the breast, chest wall, or accessible regional lymph nodes, will be evaluated for image-guided core biopsies of liver metastasis or video-assisted thorascopic wedge resection of lung metastasis\n\n  * In patients with early stage TNBC undergoing upfront surgery, the tumor tissue will be retrieved during lumpectomy\u002Fmastectomy. In early stage patients who are identified as high risk of having residual disease after neoadjuvant chemotherapy or undergo upfront resection, tissue will be retrieved during planned lumpectomy or mastectomy\n* Measurable disease is not required in metastatic patients but patients must have sufficient tumor to yield 1g on biopsy to enable production of personalized TMV vaccine product\n* Patients will undergo germline testing to assess for a BRCA1\u002FBRCA2 deleterious mutation. Knowledge of germline status is not required to enroll on the study\n* Able and willing to complete the entire study according to the study schedule\n* Patients must give written informed consent. A copy of the signed informed consent form will be retained in the patient's chart\n\nExclusion Criteria:\n\n* Weight of the tumor tissue is less 1 gram\n* Clinically significant comorbid conditions such as cardiovascular disease or significant peripheral vascular (e.g., uncontrolled hypertension, myocardial infarction, unstable angina) within 6 months of study entry, serious cardiac arrhythmia requiring medication, and uncontrolled infection\n* No second malignancy except prior breast cancer or except non-melanomatous skin cancer within the past 5 years\n* Ongoing or planned systemic anti-cancer therapy or radiation therapy. Last cycle of cytotoxic therapy must be \\>= 21 days prior to C1D1 of vaccine. Last cycle of checkpoint inhibitor therapy be \\>= 28 days prior to C1D1 of vaccine. Last dose of radiotherapy must be \\>= 14 days prior to C1D1 of vaccine\n* Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment\n* Has a known history of active tuberculosis (Bacillus Tuberculosis)\n* History of allogeneic organ transplant\n* Known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for management of brain metastases for at least 7 days prior to study treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability\n* Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg\u002Fday of prednisone, or an equivalent corticosteroid\n* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment\n* Known history of non-infectious pneumonitis that required steroids or any evidence of active pneumonitis\n* Failure to recover from grade 3 or 4 toxicity from previous treatment\n* For the combination cohort: prior grade 4 immune-related adverse events due to previous ICI. Patients who experienced grade 2 or 3 toxicity with prior ICI therapy may enroll if toxicity reverted to =\\\u003C grade 1",{"count":436,"type":20},18,[52],"This phase I trial tests the safety, side effects, and best dose of a personalized vaccine (tumor membrane vesicle or TMV vaccine) by itself and in combination with checkpoint inhibitor (pembrolizumab or ipilimumab) in treating patients with triple negative breast cancer. This vaccine is made by taking a piece of patient's triple negative breast cancer to design a vaccine to stimulate the immune system's memory. Patients are treated with the personalized vaccine immunotherapy with or without monoclonal antibodies, such as pembrolizumab and ipilimumab. This approach may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving personalized TMV vaccine with pembrolizumab or ipilimumab may help the immune system attack cancer better and reduce the risk of this breast cancer coming back or growing.",[440,441,442,443,444,445,55,113,114,115,26,446,140,28,447,448,449,450,451,452,453,454,455,456,336,457,67],"Anatomic Stage I Breast Cancer AJCC v8","Anatomic Stage IA Breast Cancer AJCC v8","Anatomic Stage IB Breast Cancer AJCC v8","Anatomic Stage II Breast Cancer AJCC v8","Anatomic Stage IIA Breast Cancer AJCC v8","Anatomic Stage IIB Breast Cancer AJCC v8","Early Stage Triple-Negative Breast Carcinoma","Prognostic Stage I Breast Cancer AJCC v8","Prognostic Stage IA Breast Cancer AJCC v8","Prognostic Stage IB Breast Cancer AJCC v8","Prognostic Stage II Breast Cancer AJCC v8","Prognostic Stage IIA Breast Cancer AJCC v8","Prognostic Stage IIB Breast Cancer AJCC v8","Prognostic Stage III Breast Cancer AJCC v8","Prognostic Stage IIIA Breast Cancer AJCC v8","Prognostic Stage IIIB Breast Cancer AJCC v8","Prognostic Stage IIIC Breast Cancer AJCC v8","Recurrent Breast Carcinoma","2026-01-23",{"date":460,"type":33},"2026-01-26",{"date":462,"type":33},"2025-12-02",{"date":464,"type":20},"2026-12-31",{"name":261,"class":97},4,{"id":468,"slug":469,"hasResults":11,"nctId":470,"briefTitle":471,"officialTitle":472,"acronym":473,"eligibilityCriteria":474,"healthyVolunteers":475,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":476,"targetDuration":478,"studyType":479,"phases":4,"briefSummary":480,"conditions":481,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":486,"lastUpdatePostDateStruct":487,"startDateStruct":489,"completionDateStruct":491,"leadSponsor":493,"locationsCount":98},"100575572","prospective-registry-of-adc-as-first--and-second-line-treatment-for-breast-cancer-100575572","NCT06774027","Prospective Registry of ADC as First- and Second-line Treatment for Breast Cancer","ENCORE: Multicenter ProspectivE Registry of Sequential ANtibody Drug COnjugates (ADCs) in HER2 Negative Metastatic BREast Cancer (MBC)","ENCORE","Inclusion Criteria:\n\n1. Male or female patients aged 18 years or greater with ability to provide written informed consent for this prospective registry study.\n2. Estimated life expectancy of at least at 3 months per investigator assessment.\n3. Willingness to provide an archival tissue sample and blood samples (20cc research blood collection at several timepoints) for research purposes.\n4. Cohort-specific enrollment criteria:\n\n   * Cohort 1: Histologically documented HR+\u002FHER2- MBC with plan to start an FDA-approved ADC as their first ADC per standard of care (SOC).\n   * Cohort 2: Histologically documented metastatic TNBC with plan to start an FDA-approved ADC as their first ADC per standard of care\n   * Cohort 3: Histologically documented HR+\u002FHER2- MBC with plan to start an FDA-approved ADC as their second ADC per standard of care (ADC1 should be an approved ADC administered per SOC or as monotherapy in a clinical trial; no prior experimental ADCs allowed). Clinical data from the first ADC must be available for retrospective review.\n   * Cohort 4: Histologically documented metastatic TNBC with plan to start an FDA-approved ADC as their second ADC per standard of care (ADC1 should be an approved ADC administered per standard of care or as monotherapy in a clinical trial; no prior experimental ADCs allowed). Clinical data from the first ADC must be available for retrospective review.\n   * Measurable disease is not required for any cohort.\n\nExclusion Criteria:\n\n1. Prior receipt of an experimental ADC in the metastatic setting. Of note, patients who received an FDA-approved ADC as their first ADC (as monotherapy, not in combination) can participate in cohorts 3 or 4 prior to starting their second FDA-approved ADC per standard of care. Of note, for all cohorts, experimental therapies are not allowed as intervening therapies after starting ADC1. If a patient enrolls on a clinical trial of an experimental therapy after ADC1, they will be taken off study.\n2. Current participation in a clinical trial with an ADC.\n3. Contraindication to research phlebotomy to collect \\~20cc blood at each research blood draw timepoint.",true,{"count":477,"type":20},100,"5 Years","OBSERVATIONAL","Antibody-drug conjugates (ADCs) have demonstrated substantial improvement in progression free survival (PFS) and overall survival (OS) in phase III clinical trials in patients with metastatic triple negative breast cancer (mTNBC) and hormone receptor positive\u002FHER2 negative (HR+\u002FHER2-) metastatic breast cancer (MBC), offering an effective new treatment strategy. Several outstanding questions drive the decision to use ADC drugs clinically. This is a prospective, multi-site observational study of patients with metastatic breast cancer (mBC) who are being treated with FDA-approved antibody drug conjugates (ADCs) as part of routine care and aims to collect real-world data to evaluate the impact of ADC treatment as part of routine care.",[482,483,273,484,485,28],"HER2-negative Breast Cancer","HER2 Negative Breast Carcinoma","HR+ HER2 Breast Cancer","Metastatic Triple Negative Breast Cancers","2025-12-10",{"date":488,"type":33},"2025-12-18",{"date":490,"type":33},"2025-10-08",{"date":492,"type":20},"2030-12-31",{"name":494,"class":97},"University of California, San Francisco",{"id":496,"slug":497,"hasResults":11,"nctId":498,"briefTitle":499,"officialTitle":500,"acronym":4,"eligibilityCriteria":501,"healthyVolunteers":11,"sex":246,"minAge":17,"maxAge":4,"enrollmentInfo":502,"targetDuration":4,"studyType":21,"phases":503,"briefSummary":505,"conditions":506,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":507,"lastUpdatePostDateStruct":508,"startDateStruct":510,"completionDateStruct":512,"leadSponsor":514,"locationsCount":98},"100516726","early-phase-1-neratinib-in-combination-with-ruxolitinib-in-patients-with-mtnbc-100516726","NCT06008275","Neratinib in Combination With Ruxolitinib in Patients With mTNBC","Pilot Clinical Trial Examining the Safety and Efficacy of Neratinib in Combination With Ruxolitinib in Patients With Chemotherapy-pretreated Metastatic Triple Negative Breast Cancer With Chest Wall Recurrence","Inclusion Criteria:\n\n* A patient will be considered for enrollment in this study if all the following criteria are met:\n\n  1. Female patients ≥18 years of age\n  2. Have a diagnosis of metastatic TNBC previously treated with standard anthracycline, cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to doxorubicin, in which case prior treatment with this agent is not required.\n\n     Note. TNBC defined as ER-negative tumors with ≤10% tumor nuclei immunoreactivity, or \"ER Low Positive\" as defined by the updated ASCO\u002FCAP guidelines 2020.\n  3. Have not received more than 4 prior chemotherapy regimens for metastatic disease. Prior platinum and\u002For taxane therapy in the adjuvant or metastatic setting is permitted. Patients with more than 4 prior regimens may be allowed on study per physician discretion, if ECOG PS is 0-1.\n  4. Have locoregional (e.g., breast, chest wall, regional lymphatic) or pulmonary or hepatic metastatic disease that is amenable to core needle biopsy. If a research biopsy from a patient's metastatic disease cannot be safely obtained, a skin biopsy is permitted. If a skin biopsy cannot be safely obtained, patients may still be eligible, per physician discretion.\n  5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n  6. Have adequate hematologic function, defined by:\n\n     1. Absolute neutrophil count (ANC) \\>1500\u002FµL\n     2. Platelet count ≥100,000\u002F µL\n     3. Hemoglobin ≥9 g\u002FdL or ≥5.6 mmol\u002FL\n  7. Have adequate liver function, defined by:\n\n     1. AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence of liver metastases\n     2. Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels \\>1.5 × ULN\n  8. Have adequate renal function, defined by:\n\n     a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL\u002Fmin\n  9. Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:\n  10. Brain metastases which have been treated\n  11. Off-treatment with steroids before administration of the first dose of treatment\n  12. No ongoing requirement for dexamethasone or anti-epileptic drugs\n  13. No clinical or radiological evidence of progression of brain metastases\n  14. Patients must be accessible for treatment and follow-up.\n  15. All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry.\n\nExclusion Criteria:\n\n* A patient will be ineligible for inclusion in this study any of the following criteria are met:\n\n  1. Has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study treatment. Administration of killed vaccines is allowed.\n  2. Has peripheral neuropathy ≥grade 2\n  3. Has completed previous radiotherapy for metastatic disease \\\u003C2 weeks prior to study treatment initiation\n  4. Has an active infection requiring systemic therapy\n  5. Has significant cardiovascular disease, such as:\n\n     1. History of myocardial infarction, acute coronary syndrome, or coronary angioplasty\u002Fstenting\u002Fbypass grafting within the last 6 months\n     2. Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, or history of CHF NYHA class III or IV.\n  6. Has a known history of active tuberculosis\n  7. Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.\n  8. Patients who have any severe and\u002For uncontrolled medical conditions or other conditions that could affect their participation such as:\n\n     1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and\u002For O2 saturation that is 88% or less at rest on room air\n     2. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).\n  9. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's full participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the Treating Physician.\n  10. Has received prior systemic anti-cancer therapy within 2 weeks prior to study treatment.\n  11. Has received investigational agents within 4 weeks prior to study treatment. Monoclonal antibody agents should have a 4-week (28 day) washout period.\n  12. Any other investigational or anti-cancer treatments while participating in this study\n  13. Any other active malignancy",{"count":5,"type":20},[504],"EARLY_PHASE1","The goal of this clinical trial is to assess the safety and efficacy of combined ruxolitinib and neratinib in patients with chemotherapy-pretreated metastatic triple negative breast cancer. This trial will evaluate one dosing schedule of neratinib in ruxolitinib in patients with metTNBC with locoregional recurrence.",[28,274],"2025-11-05",{"date":509,"type":33},"2025-11-10",{"date":511,"type":33},"2024-09-16",{"date":513,"type":20},"2026-12",{"name":515,"class":97},"Baylor Research Institute",{"id":517,"slug":518,"hasResults":11,"nctId":519,"briefTitle":520,"officialTitle":521,"acronym":522,"eligibilityCriteria":523,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":524,"targetDuration":4,"studyType":21,"phases":526,"briefSummary":528,"conditions":529,"keywords":530,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":534,"lastUpdatePostDateStruct":535,"startDateStruct":537,"completionDateStruct":539,"leadSponsor":541,"locationsCount":543},"100554894","telemonitoring-platform-cureety-techcare-vs-standard-of-care-for-mtbnc-patients-initiating-a-first-line-treatment-100554894","NCT06505018","Telemonitoring Platform \"CUREETY TECHCARE\" vs Standard of Care for mTBNC Patients Initiating a First-line Treatment","A Randomized Phase III Study Comparing the Digital Telemonitoring Platform \"CUREETY TECHCARE\" to Usual Standard of Care in Patients With Triple Negative Metastatic Breast Cancer Initiating a First-line Systemic Treatment","ALTERNATIVE","Inclusion Criteria:\n\n* Signed a written informed consent form prior to participate in the study. Note: In case of physical incapacitation, a trusted representative of their choice, which is not the Investigator or sponsor, can sign on the behalf of the patients\n* Patients ≥18 years of age.\n* Patient with histologically documented metastatic triple negative breast cancer (ER (Oestrogen receptor) and PR (Progesterone receptor) \\\u003C10%, Her2 negative status).\n* Life expectancy \\> 6 months as per investigator estimate.\n* Patient initiating a marketed authorized first-line systemic treatment in the metastatic setting.\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.\n* Patient having completed the EORTC QLQ-C30 and EORTC QLQ-BR45 at baseline (response to questions 29 and 30 of EORTC QLQ-C30 at baseline are mandatory)\n* Affiliated to the social security system or equivalent health insurance.\n* Patient able and willing to complete web-based self-reported questionnaires, from initiation of first-line treatment and for the duration of the study (over multiple treatment lines)\n* Patient has access to a computer, tablet, or smartphone connected to the Internet.\n\nExclusion Criteria:\n\n* Participation in another clinical trial using telemonitoring.\n* Physical or psychological incapacity of the patient to use the digital telemonitoring Cureety Techcare, according to the investigator's discretion.\n* Patient deprived of their liberty or under protective custody or guardianship.",{"count":525,"type":20},472,[527],"NA","The goal of this clinical trial is to assess whether adding telemonitoring (the digital telemonitoring platform \"CUREETY TECHCARE\"), to standard care, will benefit patients with previously untreated metastatic triple-negative breast cancer starting first-line cancer therapy.\n\nThe main questions it aims to answer are:\n\n* Is patient quality of life improved by using the telemonitoring platform?\n* Are patients hospitalized less frequently when using the telemonitoring platform?\n* Is the patient overall survival improved by telemonitoring ?\n\nResearchers will compare data from patients using telemonitoring while receiving standard care with data from patients receiving only standard care.\n\nParticipants using telemonitoring will answer questions about their symptoms on the platform. The platform will analyze these symptoms, assess the patient's general condition and provide advice accordingly. Medical staff will also access the platform to monitor the patient's general condition and contact them if necessary.",[28],[531,276,532,533],"Telemonitoring","Cureety","Adverse events","2025-08-25",{"date":536,"type":33},"2025-09-02",{"date":538,"type":33},"2024-07-25",{"date":540,"type":20},"2028-09-02",{"name":542,"class":97},"UNICANCER",51,{"id":545,"slug":546,"hasResults":11,"nctId":547,"briefTitle":548,"officialTitle":549,"acronym":4,"eligibilityCriteria":550,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":551,"targetDuration":4,"studyType":21,"phases":553,"briefSummary":554,"conditions":555,"keywords":559,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":562,"lastUpdatePostDateStruct":563,"startDateStruct":565,"completionDateStruct":567,"leadSponsor":569,"locationsCount":346},"100529629","phase-2-dato-base-datopotamab-deruxtecan-for-breast-cancer-brain-metastases-100529629","NCT06176261","DATO-BASE: DATOpotamab-deruxtecan for Breast Cancer Brain metAstaSEs","DATO-BASE: A Phase 2 Trial of DATOpotamab-deruxtecan for Breast Cancer Brain metAstaSEs","Inclusion Criteria :\n\n* Metastatic breast cancer that is pathologically confirmed to be HER2-negative according to 2018 ASCO\u002FCAP guidelines 55.\n* Radiological confirmation of metastatic disease.\n* Cohorts A and B: Presence of newly diagnosed brain metastases or brain metastases progressing after prior local and\u002For systemic therapy.\n* Cohorts A and B: Participants must have a baseline MRI of the brain performed with and without gadolinium contrast, and must have central nervous system metastases with at least one measurable brain metastasis ≥ 1.0 cm in size (per RANO-BM) that has not been irradiated, or has progressed despite prior radiation therapy and\u002For systemic therapy (in the opinion of the treating physician). For cohorts A and B, head CT with contrast may be used in place of MRI at baseline and throughout the trial if MRI is contraindicated and the participant's CNS metastases are clearly measurable by head CT.\n* Cohorts C: Radiological evidence of evaluable leptomeningeal disease and clinical diagnosis of LMD per treating investigator. A positive CSF cytology is not required.\n* Cohort A: prior progression to treatment with at least one line of endocrine treatment (with or without CDK4\u002F6 inhibition) in the metastatic setting is mandatory. Patients experiencing recurrence during adjuvant endocrine treatment will be also considered eligible for the trial. There is no limit on the number of prior lines acceptable for the purpose of enrollment in this study.\n* Cohort B and C: no prior treatment is required (i.e., previously untreated patients are eligible). There is no limit on the number of prior lines of therapy acceptable for the purpose of enrollment in this study.\n* Participants may have measurable or non-measurable extracranial disease. Participants are NOT required to have extracranial disease, but must have imaging done to document disease status at baseline.\n* Age ≥ 18 years.\n* ECOG Performance Status 0-2\n* Participants must have adequate treatment washout period before registration, defined as \\> 4 weeks from major surgery, \\> 2 weeks from radiation treatment. For weekly chemotherapy regimens, \\> 2 weeks from chemotherapy; for every 3 weekly regimens, \\> 3 weeks from chemotherapy. At least 2 weeks from other systemic or targeted or investigational therapies (other than endocrine therapy) for breast cancer. No washout is required for endocrine therapy (e.g. aromatase inhibitors, tamoxifen, fulvestrant) but patients should discontinue prior to start of protocol therapy. Patients on ovarian suppression are allowed (but not required) to continue ovarian suppression at the discretion of their treating provider.\n* Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.\n* Adequate organ function as defined by the following values:\n\n  * Hemoglobin ≥ 9.0 g\u002FdL. Red blood cell\u002Fplasma transfusion is not permitted within 1 week prior to screening assessment.\n  * Absolute neutrophil count ≥1,500\u002Fmm3. Granulocyte colony-stimulating factor administration is not permitted within 1 week prior to screening assessment.\n  * Platelets ≥100,000\u002Fmm3. Platelet transfusion is not permitted within 1 week prior to screening assessment.\n  * Total bilirubin ≤ 1.5 institutional ULN if no liver metastases; or ≤ 3 x ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.\n  * AST(SGOT)\u002FALT(SGPT) ≤ 2.5 × institutional ULN OR ≤ 5.0 x institutional ULN for patients with documented liver metastases\n  * Serum creatinine ≤ 1.5 mg\u002FdL (or glomerular filtration rate ≥ 30 ml\u002Fmin as determined by the Cockcroft-Gault equation)\n* Participants with a history of chronic viral conditions such as HIV, Hepatitis B\u002FC, should not be systemically excluded but have thoughtful consideration of inclusion, unless safety is a concern. Testing for these conditions is not required at baseline.\n* Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 14 days of initiating protocol therapy.\n* Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Visceral crisis or impending visceral crisis\n* CNS complications for whom urgent neurosurgical intervention is indicated (i.e., resection, shunt placement)\n* Indication for immediate local therapy to CNS lesion(s) as defined by local standard\n* Evidence of significant (i.e., symptomatic) intracranial hemorrhage\n\n  -\\> 2 seizures within 4 weeks prior to study entry (registration)\n* Ongoing\u002Fpersistent toxicities caused by previous anti-cancer therapy (except alopecia) not yet improved to Grade ≤ 1 OR baseline prior to study entry (registration)\n* Known contraindication to MRI (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity, hypersensitivity). However, for cohorts A and B, head CT with contrast may be used in place of MRI at baseline and throughout the trial if MRI is contraindicated and the participant's CNS metastases are clearly measurable by head CT.\n* Concurrent administration of other anti-cancer therapy during the course of this study is not allowed. Concurrent use of supportive care medications is allowed, and certain medications are required (see Section 5.1).\n* Uncontrolled intercurrent illness, including (but not limited to) active infection, severely compromised pulmonary function, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ischemic heart disease, myocardial infarction within the previous six months, gastric or duodenal ulceration diagnosed within the previous six months, chronic liver or renal disease, or severe malnutrition. Note that if a patient has controlled diabetes mellitus, but is unable to monitor blood glucose at home, they will be excluded from the trial.\n* Participants must not have a condition requiring ongoing systemic treatment with corticosteroids (\\>4 mg daily dexamethasone (or bioequivalent)) or other immunosuppressive medications within 7 days prior to the baseline MRI. Corticosteroids administration must be stable and planned to remain ≤ 4 mg daily for the duration of protocol treatment. However, use of corticosteroids for clinical symptoms is allowed based upon treating physician discretion.\n* History of non-infectious interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, current ILD\u002Fpneumonitis, or suspected ILD\u002Fpneumonitis that cannot be ruled out by imaging at screening.\n* A history of uncontrolled seizures, CNS disorders, or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs.\n* A history of malignancy other than breast cancer, except (a) adequately resected non-melanoma skin cancer, (b) curatively treated in situ disease, or (c) other solid tumors curatively treated, with no evidence of disease for ≥ 3 years.\n* Major surgery, open biopsy, or significant traumatic injury within 28 days prior to the initiation of protocol therapy, or anticipation of need for a major surgical procedure during the study.\n* Clinically significant corneal disease.\n* Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients (including but not limited to polysorbate 80) of datopotamab deruxtecan.\n* History of severe hypersensitivity reactions to other monoclonal antibodies\n* Negative pregnancy test (urine and\u002For serum) is required for women of childbearing potential. Pregnant or lactating women are excluded from participation due to potential teratogenic effects of study drug.\n* Female participants must be either:\n\n  * post-menopausal for at least 1 year\n  * surgically sterile, or\n  * if of childbearing potential and sexually active with a non-sterilized male partner, must agree to use one highly effective form of birth control for the entire treatment period and for at least 7 months after the last dose of datopotamab deruxtecan (see Section 5.4 for complete list of highly effective birth control methods).\n* Female participants must not donate, or retrieve for their own use, ova at any time during this study and for at least 7 months after the last dose of datopotamab deruxtecan.\n* Female participants must refrain from breastfeeding while on study and for at least 7 months after the last dose of datopotamab deruxtecan.\n* Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception (see Section 5.4 for complete list of highly effective birth control methods) from the time of screening throughout the total duration of the study and the drug washout period (at least 4 months after the last dose of study intervention) to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period.",{"count":552,"type":20},58,[23],"The purpose of this study is to test the safety and effectiveness of the study drug datopotamab deruxtecan in participants with metastatic breast cancer that has spread to the brain.\n\nThe name of the study drug used in this research study is:\n\nDatopotamab deruxtecan (a type of antibody-drug conjugate)",[274,556,28,557,482,483,558],"Breast Cancer Female","ER Positive Breast Cancer","ER-negative Breast Cancer",[274,556,28,557,560,483,561],"HER2 Negative Breast Cancer","ER Negative Breast Cancer","2025-07-28",{"date":564,"type":33},"2025-07-30",{"date":566,"type":33},"2024-01-08",{"date":568,"type":20},"2029-01-01",{"name":570,"class":97},"Sarah Sammons, MD",{"id":572,"slug":573,"hasResults":11,"nctId":574,"briefTitle":575,"officialTitle":576,"acronym":577,"eligibilityCriteria":578,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":579,"targetDuration":4,"studyType":21,"phases":580,"briefSummary":581,"conditions":582,"keywords":583,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":587,"lastUpdatePostDateStruct":588,"startDateStruct":590,"completionDateStruct":592,"leadSponsor":594,"locationsCount":466},"100473968","phase-1-treatment-of-advanced-or-metastatic-triple-negative-breast-cancer-with-adoptive-therapy-of-pd1-tils-100473968","NCT05451784","Treatment of Advanced or Metastatic Triple-negative Breast Cancer With Adoptive Therapy of PD1+ TILS","Treatment of Advanced or Metastatic Triple-negative Breast Cancer With Adoptive Therapy of PD1+ Tumor-infiltrating Lymphocytes (TILS001 Trial)","TILS001","Eligibility criteria for Part #1 (Molecular pre-screening: Determination of PD1 by mRNA analysis from an archival FFPE tumor sample):\n\nParticipants are eligible to be included in the study only if all of the following criteria apply:\n\n1. Age ≥ 18 years.\n2. Estimated life expectancy of ≥6 months.\n3. Histologically confirmed diagnosis of unresectable or metastatic breast cancer.\n4. Histologically confirmed diagnosis of advanced triple-negative breast cancer (based on the most recently analyzed biopsy from locally recurrent or metastatic site, local laboratory) meeting the following criteria: HER2-negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+, and ER and PgR expressions \\\u003C10% as determined locally by IHC assay as per most recent ASCO\u002FCAP guidelines.\n5. Patients could have received a maximum of 5 lines of prior standard of care chemotherapy in the inoperable\u002Fmetastatic setting.\n6. Patients must not have history of other malignancy within the past 3 years with the following exceptions: adequately treated non-melanoma skin cancer without evidence of disease at the time of enrollment; adequately treated cervical carcinoma in situ without evidence of disease at the time of enrollment; adequately treated breast ductal carcinoma in situ without evidence of disease at the time of enrollment; prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of enrollment; adequately treated superficial or in-situ carcinoma of the bladder without evidence of disease at the time of enrollment.\n7. Subject likely to be available to complete all protocol-required study visits or procedures, and\u002For to comply with all required study procedures to the best of the subject and investigator's knowledge.\n8. Absence of psychiatric or physiologic history, substance abuse, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.\n9. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n10. Pregnant or breastfeeding women will NOT be eligible.\n11. Subject has known sensitivity to any of the products or components to be administered during dosing will NOT be eligible.\n12. NOT having an immediate family member (eg, spouse, parent\u002Flegal guardian, sibling, or child) who is investigational site or sponsor staff directly involved in this trial, unless prospective institutional review board (IRB)\u002Findependent ethics committee (IEC) approval (by chair or designee) is given allowing an exception to this criterion for a specific subject\n13. Patients must NOT have undergone prior allogeneic hematopoietic stem cell transplantation\n14. Patients with a history or evidence of symptomatic autoimmune will NOT be eligible: glomerulonephritis, vasculitis, or other symptomatic autoimmune diseases, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (ie, with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma\u002Fatopy. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n15. Absence of active bacillus tuberculosis history.\n16. Absence of a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required.\n17. Absence of a known history of Hepatitis B (defined as Hepatitis B surface antigen \\[HBsAg\\] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required.\n18. To be able to provide either a newly obtained tumor biopsy (preferred) or archival tumor tissue of an FFPE tumor block. The tumor tissue should be of good quality based on total and viable tumor content and must be evaluated centrally for gene expression analysis prior to enrollment in Part #2.\n\nEligibility criteria for Part #2 (Pre-Screening Phase: Selection, isolation and partial expansion of PD1+ TILs from a fresh tumor sample):\n\nParticipants are eligible to be included in the study only if all the previous and the following criteria apply:\n\n1. Patients will be eligible for Part #2 if they have a PD-1 mRNA expression above the 20th percentile in the FFPE tumor sample analyzed in Part 1.\n2. At least 1 resectable target lesion\n3. Patients must NOT have clinically active cerebral metastases. Carcinomatous meningitis is not allowed regardless of clinical stability.\n\nEligibility criteria for Part #3 (Screening and treatment Phase: Complete expansion of PD1+TILs. Treatment of patients with PD1+ TILs infusion):\n\nParticipants are eligible to be included in the study only if all of the previous and the following criteria apply. For being included in this section, the following criteria must apply:\n\n1. PD1+ TILs selection in Part #1 and successful partial expansion of tumor sample in Part #2\n2. Treatment-related toxicities (except alopecia and neuropathy G2) must ≤ Grade 1 at the time of allocation according to CTCAE version 5.0.\n3. All patients must have received two or more prior systemic therapies, including at least one of them for advanced disease and an ADC. A maximum of five chemotherapy-based lines are permitted in the metastatic setting. Prior treatment should be discontinued 28 days or 5 half-lives, whichever is shorter, before day 1 of NMA-LD.\n4. Measurable disease according to RECIST 1.1 criteria.\n5. Adequate organ function determined within 28 days prior to enrollment.\n6. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to enrollment.\n7. For patients ≥ 60 years or patients who have a history of ischemic heart disease, chest pain, or clinically significant atrial and\u002For ventricular arrhythmias, a cardiac stress tests must be performed showing normal LVEF, NYHA functional classification \\\u003C class 1 and if any wall movement abnormalities, they must be reversible.\n8. Left ventricular ejection fraction (LVEF) ≥ 50% at baseline as determined by either ECHO or MUGA\n9. Patients must not be currently receiving treatment with another investigational device or drug study. No other investigational procedures (of any kind) are permitted while participating in this study.\n10. Systemic steroid therapy is not permitted (patients who require replacement therapy for adrenal insufficiency may be enrolled if the steroid treatment dose does not exceed 10 mg of prednisone or equivalent).\n11. Patients with evidence of clinically significant immunosuppression will NOT be eligible.\n12. Patients with evidence of (non-infectious) pneumonitis that required steroids or current pneumonitis will NOT be eligible.",{"count":5,"type":20},[52,23],"This is a prospective, multicenter, phase I\u002FII, open-label, two-stage design of PD1+ TILs infusion in metastatic or advanced TNBC. TILS001 includes 3 parts. Previous to each phase inclusion, a specific ICF must be signed by the patient. Participants potentially eligible to participate in the clinical trial will be offered to sign a ICF three times prior to TILs treatment: 1) to allow for collection of archival FFPE tissue samples for determination PD1 by mRNA (Part #1), 2) prior to a fresh metastatic biopsy for selection, isolation and partial expansion of PD1+ TILs (Part #2) and 3) prior to allow for remaining study procedures and TILs therapy (Part #3, Main Consent).",[28],[584,274,585,586],"TNBC","metastatic","triple negative","2023-11-21",{"date":589,"type":33},"2023-11-24",{"date":591,"type":33},"2022-07-20",{"date":593,"type":20},"2027-09-30",{"name":595,"class":97},"Fundacio Clinic Barcelona"]