[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-urothelial-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-urothelial-carcinoma":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,21,0,[8,41,64,106,228,257,284,325,352,379,414,436,468,504,529,559,580,604,643,665,693],{"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":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":40},"100549882","phase-1-pembrolizumab-plus-ca-4948-for-the-treatment-of-patients-with-progressive-metastatic-urothelial-cancer-despite-prior-immunotherapy-100549882",false,"NCT06439836","Pembrolizumab Plus CA-4948 for the Treatment of Patients With Progressive Metastatic Urothelial Cancer Despite Prior Immunotherapy","Phase 1 Trial of CA-4948 in Combination With Pembrolizumab to Overcome Resistance to PD-1\u002FPD-L1 Blockade in Metastatic Urothelial Cancer","Inclusion Criteria:\n\n* Patients must have histologically confirmed urothelial cancer that is metastatic or unresectable and must have had the prior treatments outlined\n* Age ≥ 18 years\n\n  * Because no dosing or adverse event data are currently available on the use of CA-4948 in combination with pembrolizumab 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 ≤ 2 (Karnofsky ≥ 60%) within 28 days prior to registration\n* Leukocytes ≥ 3,000\u002FmcL\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL\n* Platelets ≥ 100,000\u002FmcL\n* Hemoglobin ≥ 9 g\u002FdL or ≥ 5.6 mmol\u002FL\n\n  * Criteria must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin (≥ approximately 3 months)\n* Creatine phosphokinase (CPK) \\\u003C grade (Gr) 2 ( \\\u003C\u002F= 2.5 upper limit of normal \\[ULN\\])\n* Creatinine \\\u003C 1.5 × institutional ULN or creatinine clearance of ≥ 30 mL\u002Fmin for patient with creatine levels ≥ 1.5 x institutional ULN\n\n  * Creatinine clearance (CrCl) should be calculated per institutional standard\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) ≤ 3 x ULN\n* Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 x ULN\n* International normalized ratio (INR) or prothrombin time (PT) ≤ 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) ≤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\n* Ability to provide at least 20 unstained slides or formalin-fixed paraffin-embedded (FFPE) block plus 1 hematoxylin and eosin (H\\&E) slide from prior archival invasive urothelial cancer specimen (and\u002For ability to undergo baseline tumor biopsy in patients in the expansion cohort)\n* Measurable metastatic or unresectable disease\n* Must have received prior treatment with a PD-1 or PD-L1 inhibitor\n* Must have received at least one of the following (may have been administered concurrently or sequentially with PD-1\u002FPD-L1 inhibitor):\n\n  * Platinum-based chemotherapy\n  * Enfortumab vedotin\n* Primary resistance to PD-1\u002FPD-L1 blockade as defined by Society for Immunotherapy of Cancer (SITC) consensus definitions:\n\n  * For patients who received single-agent PD-1\u002FPD-L1 blockade in the adjuvant setting:\n\n    * Must have received ≥ 6 weeks of treatment with PD-1\u002FPD-L1 blockade\n    * Recurrence while on treatment or within ≤ 3 months after completion of therapy\n  * For patients who received single-agent PD-1\u002FPD-L1 blockade in the metastatic setting:\n\n    * Must have received ≥ 6 weeks of treatment with PD-1\u002FPD-L1 blockade\n    * Progression within ≤ 6 months of initiating treatment with single-agent PD-1\u002FPD-L1 blockade with best response of stable disease\n  * For patients who received single-agent PD-1\u002FPD-L1 blockade in the switch-maintenance setting:\n\n    * Must have received ≥ 6 weeks of treatment with PD-1\u002FPD-L1 blockade\n    * Progression within ≤ 6 months of initiating treatment with single-agent PD-1\u002FPD-L1 blockade\n  * For patients who received an antibody-drug conjugate or cytotoxic chemotherapy plus PD-1\u002FPD-L1 blockade combination\n\n    * Must have received ≥ 6 weeks of treatment with PD-1\u002FPD-L1 blockade\n    * Progression within ≤ 12 months of initiating treatment\n  * An eligibility form will be developed to include documentation of the dates of prior PD-1\u002FPD-L1 blockade and a redacted radiology report confirming best response of stable disease for \\\u003C 6 months or progressive disease)\n* Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient\n* Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient\n* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Patients who have received messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) and influenza vaccines will be allowed\n* Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either magnetic resonance imaging \\[MRI\\] or computed tomography \\[CT\\] scan, for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment\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\n* Patients should be willing and able to swallow pills\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) Note: Patients with grade ≤ 2 neuropathy or grade ≤ 2 alopecia are an exception to this criterion and may qualify for the study. Note: If patients received major surgery, they must have recovered adequately from the toxicity and\u002For complications from the intervention prior to starting therapy\n* 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 the first dose of study drug\n* Grade ≥ 3 immune related adverse event with prior PD-1\u002FPD-L1 blockade\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CA-4948 and\u002For pembrolizumab\n* Patients with uncontrolled intercurrent illness, including but not limited to interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia that would limit compliance with study requirements\n* Patients who are receiving any other investigational agents\n* Patients with carcinomatous meningitis\n* Patients with malabsorption syndrome or other conditions that would interfere with intestinal absorption\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* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis\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 patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator\n* Has received a live vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted\n* Pregnant women are excluded from this study because pembrolizumab is a monoclonal antibody with 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 pembrolizumab, breastfeeding should be discontinued if the mother is treated with pembrolizumab. These potential risks may also apply to other agents used in this study\n* Has known active hepatitis B (e.g., hepatitis B surface antigen \\[HBsAg\\] reactive) or hepatitis C (e.g., hepatitis C virus \\[HCV\\] RNA \\[qualitative\\] is detected)\n* Has a known history of active tuberculosis (TB)","ALL","18 Years",{"count":19,"type":20},27,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","This phase I trial tests the safety, side effects, best dose, and effectiveness of emavusertib (CA-4948) in combination with pembrolizumab in treating patients with urothelial cancer that has spread from where it first started to other places in the body (metastatic) and that has a resistance to PD-1\u002FPD-L1 immune checkpoint inhibitors. CA-4948, a kinase inhibitor, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving CA-4948 in combination with pembrolizumab may be safe, tolerable and\u002For effective in treating patients with metastatic urothelial cancer that is resistant to PD-1\u002FPD-L1 immune checkpoint inhibitors.",[26,27],"Metastatic Urothelial Carcinoma","Unresectable Urothelial Carcinoma","RECRUITING","2026-06-30",{"date":31,"type":32},"2026-07-01","ACTUAL",{"date":34,"type":32},"2025-05-05",{"date":36,"type":20},"2027-06-01",{"name":38,"class":39},"National Cancer Institute (NCI)","NIH",11,{"id":42,"slug":43,"hasResults":11,"nctId":44,"briefTitle":45,"officialTitle":46,"acronym":4,"eligibilityCriteria":47,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":48,"targetDuration":4,"studyType":21,"phases":50,"briefSummary":52,"conditions":53,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":55,"lastUpdatePostDateStruct":56,"startDateStruct":58,"completionDateStruct":60,"leadSponsor":62,"locationsCount":63},"100556395","phase-3-a-study-comparing-the-combination-of-pembrolizumab-and-sacituzumab-govitean-hziy-versus-standard-of-care-in-the-treatment-of-advanced-urothelial-cancer-100556395","NCT06524544","A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitean-hziy Versus Standard of Care in the Treatment of Advanced Urothelial Cancer","A Phase III Randomized Trial of Pembrolizumab in Combination With Sacituzumab Govitean-hziy vs Standard of Care in Anti-PD(L)1-Resistant Advanced Urothelial Cancer","Inclusion Criteria:\n\n* Patient must be ≥ 18 years of age\n* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.\n* Patient must have locally advanced (unresectable and\u002For not amenable to curative intent therapy) or metastatic urothelial cancer\n* Patient must have histologically proven conventional urothelial carcinoma (UC) of any urinary tract origin \\[any histologic subtype except neuroendocrine (small or large cell)\\] are permitted so long as tumors include ≥ 1% conventional urothelial histology). NOTE: Pure non-urothelial histology is excluded\n* Patient must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Baseline imaging must be obtained ≤ 35 days prior to randomization\n* Patient must have the following prior treatment(s). Patient must have had progression on or after the immediate prior anti-cancer therapy\n* Patient must have had prior exposure to anti-PD(L)1 therapy \\[anti -PD(L)1 monotherapy or as a combination regimen in any disease\u002Ftherapy setting for UC\\]. Patients must have received at least 1 dose of anti-PD(L)1 therapy\n\n  * NOTE: Anti-PD(L)1 therapy does not need to be the most recent therapy received prior to enrollment on this protocol\n  * NOTE: Patient must not have had progression within 12 weeks of starting their first anti-PD(L) 1 therapy, even if anti-PD-(L)1 treatment was given in more than one lines of therapy\n* Patient must have had ≥ 1 line of systemic therapy given in the advanced\u002Fmetastatic disease setting, except for patients who had received anti-PD(L)1 + enfortumab vedotin in the localized disease setting (e.g., neoadjuvant and\u002For adjuvant) and had cancer progression within 12 months from the last systemic therapy dose\n* For tumors with known FGFR3+ susceptible alteration (for FGFR inhibitor), patients must have received a prior FGFR inhibitor unless contraindicated per physician discretion\n* Patient must have received prior enfortumab vedotinor any other Nectin-4 directed therapy or other MMAE-containing therapy in any disease\u002Ftherapy setting unless contraindicated per physician\n* Patient must have had no prior exposure to Sacituzumab govitean-hziy or other TROP-2 directed therapies or antibody-drug conjugate that contains topo-isomerase I inhibitor, e.g. trastuzumab deruxtecan\n* Patient must have Bellmunt score of 0-2. The Bellmunt score assesses a patient's risk and is calculated based on ECOG PS, hemogloblin level and presence of liver metastases\n* Patient must not have history of grade 3 or higher immune-related adverse events on prior anti-PD1\u002FL1, except for endocrinopathies on adequate hormone therapy repletion and\u002For clinically insignificant laboratory abnormalities\n* Patient must have recovered (i.e., ≤ grade 1) from clinically significant AEs due to previously administered systemic therapy agent, except for endocrinopathies on adequate hormone therapy repletion\n\n  * NOTE: Patients with ≤ grade 2 neuropathy, any grade of alopecia, or any grade of non-clinically significant laboratory abnormality are exceptions to this criterion and are allowed in this trial.\n  * Examples of non-clinically significant laboratory abnormalities include, but are not limited to:\n\n    * Lymphopenia or monopenia\n    * Lymphocytosis or monocytosis\n    * Increase in amylase or lipase with no clinical correlation\n    * Any other abnormal laboratory findings that have no clinical relevance per the treating investigator.\n  * NOTE: If patient has undergone major surgery, they must have recovered adequately from the toxicity and\u002For complications from the intervention prior to randomization\n* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Patient must not nurse infants while on protocol treatment and for 4 months after the last dose of protocol treatment\n* Patient must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Patients of childbearing potential must continue contraceptive method(s) or abstain for 6 months after the last dose of protocol treatment. Patients with partners who could become pregnant should use effective contraception during therapy and for 3 months after the last dose of protocol treatment\n* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and\u002For family member available will also be considered eligible\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FuL (obtained ≤ 14 days prior to randomization)\n* Platelets ≥ 100,000\u002FuL (obtained ≤ 14 days prior to randomization)\n* Albumin ≥ 3 g\u002FdL (obtained ≤ 14 days prior to randomization)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 14 days prior to randomization)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 × institutional ULN or ≤ 5.0 x institutional ULN if known liver metastases (obtained ≤ 14 days prior to randomization)\n* Creatinine clearance (CrCl) ≥ 30 mL\u002Fmin (obtained ≤ 14 days prior to randomization) NOTE: CrCl is estimated using the Cockcroft-Gault formula (or can be measured by 24-hour urine collection if needed)\n* Hemoglobin (Hb) ≥ 8.5 mg\u002Fdl (obtained ≤ 14 days prior to randomization)\n* Patient must not have a known genetic UGT1A1 deficiency (Gilbert's syndrome). Patients with variant type UGT1A1\\*28 allele may have increased levels of SN-38 metabolite (due to reduced SN-38 metabolism and clearance) and are at higher risk for severe adverse events when compared to wild-type.\n\n  * NOTE: If a patient's UGT1A1 status is unknown, they are eligible to enroll (the study does not require this test as part of screening)\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible\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 history of hepatitis C virus (HCV) infection must have been treated and considered 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 and are not using steroids \\> 10 mg of prednisone (or equivalent) daily for brain metastases for at least 7 days prior to randomization\n* Patients with prior or concurrent malignancy that is not considered clinically significant and whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (at the discretion of the treating physician) are eligible\n* Patient must not be on systemic immunosuppressive medication, including steroids (if doses exceed the equivalent of prednisone 10 mg daily). Short courses of steroids, e.g. \"burst\", which are discontinued prior to randomization are acceptable. Patients on inhaled, intranasal, intra-articular and\u002For topical steroids are eligible\n* Patient must be English or Spanish speaking to be eligible for the HRQOL component of the study.\n\n  * NOTE: Sites cannot translate the associated HRQOL forms",{"count":49,"type":20},320,[51],"PHASE3","This phase III trial compares the effectiveness of pembrolizumab and sacituzumab govitean-hziy to standard of care in treating patients with urothelial cancer that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread to other places in the body (metastatic). 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. Sacituzumab govitean-hziy is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug called govitean-hziy. Sacituzumab attaches to TROP2 positive tumor cells in a targeted way and delivers govitean-hziy to kill them. The usual treatment approach is treatment with chemotherapy such as cisplatin, carboplatin, gemcitabine, docetaxel or paclitaxel. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Giving pembrolizumab and sacituzumab govitean-hziy may be more effective than usual care of carboplatin or cisplatin with gemcitabine, docetaxel or paclitaxel in treating patients with locally advanced or metastatic urothelial cancer.",[54,26,27],"Locally Advanced Urothelial Carcinoma","2026-06-24",{"date":57,"type":32},"2026-06-25",{"date":59,"type":32},"2025-12-02",{"date":61,"type":20},"2028-12-31",{"name":38,"class":39},152,{"id":65,"slug":66,"hasResults":11,"nctId":67,"briefTitle":68,"officialTitle":69,"acronym":4,"eligibilityCriteria":70,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":71,"targetDuration":4,"studyType":21,"phases":73,"briefSummary":75,"conditions":76,"keywords":81,"overallStatus":94,"whyStopped":4,"lastUpdateSubmitDate":95,"lastUpdatePostDateStruct":96,"startDateStruct":98,"completionDateStruct":100,"leadSponsor":102,"locationsCount":105},"100644477","early-phase-1-imaging-study-of-a-trop2-binder-in-metastatic-uc-hr-and-her2--breast-cancer-tnbc-and-nsclc-100644477","NCT07671092","Imaging Study of a TROP2 Binder in Metastatic UC, HR+ and HER2- Breast Cancer, TNBC, and NSCLC","A Phase 0 Imaging Study to Assess the Feasibility, Biodistribution, and Dosimetry of a Trophoblast Cell Surface Antigen 2 (TROP2) Binder in Metastatic Urothelial Cancer (UC), Hormone Receptor-Positive (HR+) and Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Breast Cancer, Triple-Negative Breast Cancer (TNBC), and Non-Small-Cell Lung Cancer (NSCLC)","Inclusion Criteria:\n\n* Are at least 18 years old at the time of signing the informed consent form (ICF)\n* Have biopsy proven metastatic UC, HR+ and HER2- breast cancer, TNBC, or NSCLC\n\nExclusion Criteria:\n\n* TROP2-targeting antibody-drug conjugates (ADCs) such as sacituzumab govitecan or datopotamab deruxtecan, should be discontinued at least 90 days prior to administration of RYZ211 and RYZ212\n* For Women of Childbearing Potential: Are pregnant or breastfeeding\n\nNote: Additional criteria may apply and will be assessed by the study site",{"count":72,"type":20},40,[74],"EARLY_PHASE1","This imaging study aims to assess the feasibility, biodistribution, and dosimetry of a TROP2 binder in subjects with metastatic UC, HR+ and HER2- breast cancer, TNBC, or NSCLC.",[26,77,78,79,80],"Breast Cancer","TNBC - Triple-Negative Breast Cancer","Hormone Receptor Positive HER-2 Negative Breast Cancer","NSCLC",[82,83,77,84,85,86,87,88,89,90,91,92,93],"HR+","HER2-","Non Small Cell Lung Cancer","Triple Negative Breast Cancer","Trop2","TNBC","RayzeBio","Rayze","BMS","Bristol Myers Squibb","RPT","Imaging Agent","NOT_YET_RECRUITING","2026-06-22",{"date":97,"type":32},"2026-06-26",{"date":99,"type":20},"2026-06",{"date":101,"type":20},"2027-10",{"name":103,"class":104},"RayzeBio, Inc.","INDUSTRY",1,{"id":107,"slug":108,"hasResults":11,"nctId":109,"briefTitle":110,"officialTitle":111,"acronym":112,"eligibilityCriteria":113,"healthyVolunteers":11,"sex":16,"minAge":114,"maxAge":4,"enrollmentInfo":115,"targetDuration":4,"studyType":21,"phases":117,"briefSummary":119,"conditions":120,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":218,"lastUpdatePostDateStruct":219,"startDateStruct":221,"completionDateStruct":223,"leadSponsor":225,"locationsCount":105},"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":116,"type":20},132,[23,118],"PHASE2","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.",[121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,54,156,157,158,159,160,161,162,163,164,165,166,167,168,26,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,27,213,214,215,216,217],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Anatomic Stage IV 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","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 Malignant Solid Neoplasm","Metastatic Melanoma","Metastatic Merkel Cell Carcinoma","Metastatic Renal Cell Carcinoma","Metastatic Skin Squamous Cell Carcinoma","Metastatic Triple-Negative Breast 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 Malignant Solid Neoplasm","Unresectable Melanoma","Unresectable Merkel Cell Carcinoma","Unresectable Renal Cell Carcinoma","Unresectable Skin Squamous Cell Carcinoma","Unresectable Triple-Negative Breast 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":220,"type":32},"2026-06-23",{"date":222,"type":32},"2022-03-31",{"date":224,"type":20},"2028-03-31",{"name":226,"class":227},"Mayo Clinic","OTHER",{"id":229,"slug":230,"hasResults":11,"nctId":231,"briefTitle":232,"officialTitle":233,"acronym":234,"eligibilityCriteria":235,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":236,"targetDuration":4,"studyType":21,"phases":238,"briefSummary":239,"conditions":240,"keywords":244,"overallStatus":94,"whyStopped":4,"lastUpdateSubmitDate":249,"lastUpdatePostDateStruct":250,"startDateStruct":251,"completionDateStruct":253,"leadSponsor":255,"locationsCount":105},"100644360","phase-2-sacituzumab-tirumotecan-vs-mmae-adcs-in-advanced-urothelial-carcinoma-fuscc-spare-uc-01-100644360","NCT07662863","Sacituzumab Tirumotecan vs MMAE-ADCs in Advanced Urothelial Carcinoma (FUSCC-SPARE-UC-01)","A Randomized, Open-label, Phase II Study Evaluating the Neurotoxicity and Efficacy of Sacituzumab Tirumotecan (Sac-TMT) Versus MMAE-based ADCs in Patients With Advanced Urothelial Carcinoma: The SPARE-UC-01 Trial","SPARE-UC-01","Inclusion Criteria\n\n1. Must voluntarily sign the written Institutional Review Board (IRB)\u002FEthics Committee (EC) approved informed consent form (ICF) prior to any screening procedures.\n2. Age \\> 18 years at the time of signing the ICF.\n3. Histologically or cytologically confirmed locally advanced (unresectable) or metastatic urothelial carcinoma (UC), including bladder, ureter, renal pelvis, or urethra. Participants with mixed histology are eligible provided that UC is the predominant component (\\> 50%).\n4. Must have received at least one prior line of systemic therapy for locally advanced or metastatic UC (e.g., Enfortumab Vedotin plus Pembrolizumab, Disitamab Vedotin plus Toripalimab, platinum-based chemotherapy, immune checkpoint inhibitors, Nectin-4 ADCs, HER2 ADCs, FGFR inhibitors, or other palliative chemotherapy regimens).\n5. Neuropathy Status:\n\n   Cohort A\u002FB: Baseline peripheral neuropathy (PN) Grade 0-1 (per NCI-CTCAE v5.0) with stable nerve function confirmed by Nerve Conduction Study (NCS) during screening.\n\n   Cohort C (Observational): Baseline PN Grade 2, or a history of PN \\> Grade 2 where the investigator deems the patient unsuitable for MMAE-based ADC treatment.\n6. At least one measurable lesion per RECIST v1.1. (Lesions in previously irradiated areas are considered target lesions only if clear progression is documented after radiotherapy).\n7. ECOG Performance Status of 0 or 1 at screening.\n8. Expected survival \\> 3 months.\n9. Must have adequate organ and bone marrow function (no blood transfusion, growth factors, or albumin support within 14 days prior to screening):\n\n   * Hematological: ANC \\>= 1.5 x 10\\^9\u002FL; Platelets \\>= 75 x 10\\^9\u002FL; Hemoglobin \\>= 90 g\u002FL.\n   * Hepatic: ALT and AST \\\u003C= 2.5 x ULN (or \\\u003C= 5 x ULN for patients with liver metastases); Total Bilirubin \\\u003C= 1.5 x ULN (if Total Bilirubin \\> 1.5 x ULN, Direct Bilirubin must be \\\u003C= ULN).\n   * Coagulation: INR \\\u003C= 1.5; APTT \\\u003C= 1.5 x ULN; PT \\\u003C ULN + 4 seconds.\n   * Renal: Creatinine Clearance (CrCl) \\>= 30 mL\u002Fmin, or Serum Creatinine \\\u003C= 1.5 x ULN.\n\nExclusion Criteria\n\n1. Prior treatment with TROP2-targeted ADCs, topoisomerase I inhibitors (e.g., irinotecan, topotecan), or ADCs containing topoisomerase I inhibitor payloads.\n2. Patients previously treated with both Enfortumab Vedotin (EV) and Disitamab Vedotin (DV) are excluded from Cohorts A and B (eligible for Cohort C only).\n3. Treatment with any investigational anti-tumor agents, chemotherapy, immunotherapy, monoclonal antibodies, targeted therapy, or radical radiotherapy within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose. Major surgery within 4 weeks prior to the first dose.\n4. Active CNS or meningeal metastases. Patients with previously treated CNS metastases are eligible if clinically stable for ≥ 4 weeks, off systemic corticosteroids for ≥ 2 weeks (physiological replacement ≤ 10 mg\u002Fday prednisone equivalent is allowed), and no evidence of radiographic progression.\n5. History of non-infectious pneumonitis\u002Finterstitial lung disease (ILD) requiring steroids. Current ILD or suspected ILD on screening chest CT (even if asymptomatic). Severe COPD, severely impaired lung function, or requirement for long-term oxygen therapy.\n6. QTcF interval \\> 470 ms (females) or \\> 450 ms (males). Within 6 months prior to the first dose: myocardial infarction, unstable angina, severe arrhythmia requiring intervention, uncontrolled hypertension, stroke, or TIA. NYHA Class III or IV congestive heart failure.\n7. Active keratitis, corneal ulcer, or severe dry eye syndrome.\n8. Active Hepatitis B (HBsAg positive and HBV-DNA \\> 2000 IU\u002FmL; patients with lower HBV-DNA must receive antiviral therapy); Active Hepatitis C (HCV antibody and RNA positive); Known HIV infection; Severe infection requiring IV antibiotics within 2 weeks prior to first dose.\n9. Hypersensitivity: Known severe hypersensitivity to sac-TMT, EV, DV, or their excipients.\n10. Any severe or uncontrolled systemic disease that, in the investigator's opinion, increases the risk to the participant.\n11. HbA1c ≥ 8% (Patients with well-controlled blood glucose, fasting glucose ≤ 10 mmol\u002FL, and investigator approval are eligible).\n12. History of allogeneic stem cell transplant or solid organ transplant.\n13. Pregnant or breastfeeding females.",{"count":237,"type":20},75,[118],"The main goal of this clinical trial is to learn if a new targeted cancer drug called sacituzumab tirumotecan (sac-TMT) works to treat cancer while causing less nerve damage in patients with advanced urothelial carcinoma who have progressed on or could not tolerate previous treatment such as enfortumab vedotin plus pembrolizumab (EVP) or disitamab vedotin plus toripalimab (DVT).\n\nThe main question it aims to answer is: Does sac-TMT lower the risk of getting severe nerve damage, as measured together by doctors, machines, and the participants?\n\nResearchers will compare sac-TMT to alternative MMAE-based ADC drugs (switching to a different MMAE-based ADC after the first one stopped working) to see if sac-TMT causes less nerve damage while still effectively treating the cancer. A small group of participants who had to stop their previous MMAE-based ADC treatment because of nerve damage will also receive sac-TMT to learn if the drug is safe for their nerves.\n\nParticipants will:\n\n1. Receive either sac-TMT or another MMAE-based ADC drug\n2. Have regular physical exams by a doctor to check their nerves\n3. Have machine tests to measure how well their nerves work\n4. Answer survey questions about their pain, numbness, and daily activities",[241,26,242,243],"Bladder Cancer","Urothelial Carcinoma","Peripheral Neuropathy",[243,245,246,247,248],"Sacituzumab Tirumotecan","Enfortumab Vedotin","MMAE","Disitamab Vedotin","2026-06-17",{"date":220,"type":32},{"date":252,"type":20},"2026-07-15",{"date":254,"type":20},"2029-12-01",{"name":256,"class":227},"Fudan University",{"id":258,"slug":259,"hasResults":11,"nctId":260,"briefTitle":261,"officialTitle":262,"acronym":4,"eligibilityCriteria":263,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":264,"targetDuration":4,"studyType":21,"phases":266,"briefSummary":267,"conditions":268,"keywords":270,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":249,"lastUpdatePostDateStruct":277,"startDateStruct":278,"completionDateStruct":279,"leadSponsor":281,"locationsCount":283},"100630157","phase-1-study-of-gb-4362-with-enfortumab-vedotin-and-pembrolizumab-for-advanced-urothelial-cancer-100630157","NCT07484022","Study of GB-4362 With Enfortumab Vedotin and Pembrolizumab for Advanced Urothelial Cancer","A Phase 1, Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of GB-4362 Administered With Enfortumab Vedotin and Pembrolizumab in Participants With Advanced Urothelial Cancer","Inclusion Criteria\n\n* Planned to receive standard-of-care treatment with enfortumab vedotin (EV) (starting dose 1.25 mg\u002Fkg) in combination with pembrolizumab for locally advanced or metastatic urothelial cancer.\n* Age ≥18 years.\n* ECOG Performance Status score of 0 or 1 (ECOG 2 excluded in Dose Escalation but allowed in Dose Expansion).\n* Weight ≥50 kg at screening.\n* Life expectancy ≥3 months, as determined by the investigator.\n* Participants must provide written informed consent before any study-related activities are carried out and must be able to understand the nature and purpose of the study, including potential risks and adverse effects.\n* Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.\n\nExclusion Criteria\n\n* Previously received enfortumab vedotin (EV) or other MMAE-based antibody-drug conjugates (ADCs).\n* Received anti-cancer treatment with chemotherapy, biologics, or investigational agents within 4 weeks before the first dose of EV\u002Fpembrolizumab.\n* Uncontrolled diabetes.\n* Active CNS metastases. Participants with treated CNS metastases are permitted if all of the following criteria are met:\n* CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis.\n* The participant is on a stable dose of ≤10 mg\u002Fday of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment).\n* The participant does not have leptomeningeal disease.\n* Ongoing clinically significant toxicity associated with prior treatment (including radiotherapy or surgery) that has not resolved to Grade ≤1 or returned to baseline.\n* History of a severe (Grade ≥3) allergic or infusion-related reaction to any monoclonal antibody.\n* Another underlying medical condition that, in the opinion of the investigator, would impair the ability of the participant to receive or tolerate the planned treatment and follow-up.\n* Known psychiatric or substance abuse disorders that would interfere with cooperating with study requirements",{"count":265,"type":20},37,[23],"The purpose of this study is to evaluate the safety and tolerability of an investigational drug called GB-4362 when it is given together with enfortumab vedotin and pembrolizumab in adults with advanced or metastatic urothelial cancer. GB-4362 is a monoclonal antibody designed to bind and neutralize free monomethyl auristatin E (MMAE), a chemotherapy payload released from enfortumab vedotin that is associated with side effects such as peripheral neuropathy.",[269,26],"Advanced Urothelial Cancer",[271,246,272,243,273,247,274,275,276],"GB-4362","Pembrolizumab","Antibody-Drug Conjugate","Phase 1 Oncology","Dose Escalation","Dose Expansion",{"date":218,"type":32},{"date":99,"type":20},{"date":280,"type":20},"2027-12",{"name":282,"class":104},"Generate Biomedicines",10,{"id":285,"slug":286,"hasResults":11,"nctId":287,"briefTitle":288,"officialTitle":289,"acronym":4,"eligibilityCriteria":290,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":291,"targetDuration":4,"studyType":21,"phases":293,"briefSummary":294,"conditions":295,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":317,"lastUpdatePostDateStruct":318,"startDateStruct":320,"completionDateStruct":322,"leadSponsor":324,"locationsCount":105},"100536473","phase-2-comparison-of-in-home-versus-in-clinic-administration-of-subcutaneous-nivolumab-through-cancer-care-connected-access-and-remote-expertise-beyond-walls-ccbw-program-100536473","NCT06265285","Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program","MC230716 Pilot Single-Arm, Pragmatic Trial Of In-Home Versus In-Clinic Subcutaneous Nivolumab Administration Through Cancer CARE (Connected Access And Remote Expertise) Beyond Walls (CCBW) Program","Inclusion Criteria:\n\n* Age ≥ 18 years\n* Histologically confirmed malignancies for which treatment with intravenous nivolumab is currently Food and Drug Administration (FDA) approved and who are recommended to initiate a new treatment regimen with single agent intravenous (IV) nivolumab by their treating oncologist for any of the indications outlined below and who are willing to switch to subcutaneous nivolumab. Additionally, patients who are currently receiving single-agent IV nivolumab are eligible, provided they transition to subcutaneous nivolumab on-study, with their first subcutaneous (subQ) dose administered on cycle 1, day 1 of the study.\n\n  * Single agent nivolumab administered in the adjuvant setting for one of the following indications:\n\n    * Completely resected stage IIB\u002FC, III or IV melanoma\n    * Urothelial carcinoma status post radical resection and have a high risk of recurrence\n    * Completely resected esophageal or gastroesophageal junction carcinoma with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT)\n  * Single agent nivolumab for advanced\u002Fmetastatic cancer for one or more of the following indications:\n\n    * Renal cell carcinoma (RCC) patients who have received prior anti-angiogenic therapy\n    * Non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (Note: patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab)\n    * Unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy\n    * Unresectable or metastatic cutaneous melanoma\n    * Locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy\n    * Unresectable or metastatic urothelial carcinoma, as first-line treatment in combination with cisplatin and gemcitabine.\n\n      * Subcutaneous nivolumab to be initiated as monotherapy following six cycles of cisplatin + gemcitabine\n    * Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy\n    * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan\n  * Patients transitioning to maintenance nivolumab and who are willing to switch to subcutaneous nivolumab after completion of Ipilimumab and nivolumab combination therapy for one or more of the indications listed below (Note: patients who discontinue ipilimumab for immune-related toxicities, but are deemed to be eligible to continue on single agent nivolumab maintenance by their treating oncologist are eligible):\n\n    * First-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC)\n    * Unresectable or metastatic cutaneous melanoma\n    * Hepatocellular carcinoma (HCC) previously treated with sorafenib\n    * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan\n  * Single agent nivolumab administered in the adjuvant setting following neoadjuvant nivolumab with platinum doublet chemotherapy for patients with resectable (tumors ≥ 4 cm and\u002For node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements\n* Patients have recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and\u002For surgery (i.e., residual toxicity no worse than grade 1 \\[grade 2 treatment-associated peripheral neuropathy, grade 2 fatigue and\u002For any grade of alopecia are acceptable assuming all other inclusion criteria are met\\]) before registration\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1\n* Aspartate transaminase (AST) values ≤ 3 × the upper limit of normal (ULN). For patients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase\n* Alanine transaminase (ALT) values ≤ 3 x the upper limit of normal (ULN). For patients with documented baseline liver metastasis, the following limits will apply: 5 x ULN for transaminase\n* Serum total bilirubin values of ≤ 1.5 x ULN ( ≤ 2 x ULN for patients with known Gilbert's syndrome). For patients with documented baseline liver metastasis, the following limits will apply: 2 x ULN for bilirubin\n* Absolute neutrophil count (ANC) of ≥ 1500\u002FμL\n* Platelet count of ≥ 100,000\u002FμL\n* Hemoglobin of ≥ 9 g\u002FdL (patients may be transfused to this level, if necessary, but transfusion must occur \\> 1 week prior to registration)\n* Serum creatinine ≤ 2.0 x the ULN for the reference laboratory or a calculated creatinine clearance of ≥ 30 mL\u002Fmin by the Cockcroft-Gault Equation measured ≤ 7 days prior to registration\n* Patients are residing ≤ 35 miles of clinic (hub) or within the area serviced by supplier and paramedic network\n* Residence has Wi-Fi to enable a reliable connection with the remote command center\n* Patients have signed Informed Consent Form (ICF)\n* Patients are willing and able to comply with the study protocol in the investigator's judgment\n* Patients are able and willing to complete study questionnaire(s) by themselves or with assistance\n* Women of childbearing potential (WOCBP) must:\n\n  * Have a negative pregnancy test (serum or urine) ≤ 3 days before the first dose of study drug\n  * Be agreeable to use a contraceptive method that is highly effective during the intervention period and for at least 5 months after the last dose and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time period\n\nExclusion Criteria:\n\n* Patients receiving any other investigational or standard of care agent which would be considered as a treatment for the primary neoplasm and is not part of the eligible treatment regimen\n* Patients requiring 24\u002F7 assistance with activities of daily living (ADLs)\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Cardiac arrhythmia\n  * Myocardial infarction ≤ 6 months\n  * Wound healing disorder\n  * Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Patients with any severe infection ≤ 4 weeks prior to registration including, but not limited to, hospitalization for complications of infections\n* Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of 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 with a condition requiring systemic treatment with either corticosteroids ( \\> 10 mg daily prednisone equivalent) ≤ 14 days or other immunosuppressive medications ≤ 30 days prior to registration. Inhaled or topical steroids, and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease\n* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active ≤ 2 years prior to registration (i.e., participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before randomization\u002Ftreatment assignment and the patient has no evidence of disease). Participants with history of prior early stage basal\u002Fsquamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are also eligible\n* Patients have undergone prior solid organ and\u002For non-autologous hematopoietic stem cell or bone marrow transplant\n* Patients with active brain metastases or leptomeningeal metastases, aside from the exceptions below. Participants with brain metastases are eligible if they are:\n\n  * Asymptomatic\n  * Have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the central nervous system \\[CNS\\] treatment), and\n  * There is no MRI evidence of progression for at least 4 weeks after CNS directed therapy is complete and ≤ 28 days prior to registration\n  * In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to registration\n* Participants with brain disease treated with whole brain radiation\n* Anticipation of the need for major surgery during the course of study treatment\n* Participants who are pregnant or breastfeeding\n* Treatment with any live attenuated vaccines ≤ 30 days of registration (vaccines that are not live attenuated are allowed, including COVID-19 vaccine)\n* Known human deficiency virus (HIV) positive with an AIDS defining opportunistic infection within the last year, or a current CD4 count \\\u003C 350 cells\u002FuL, aside from the exceptions below. Participants with HIV are eligible if:\n\n  * They have received antiviral therapy (ART) for at least 4 weeks prior to treatment assignment as clinically indicated while enrolled in the study\n  * They continue on ART as clinically indicated while enrolled on study\n  * CD4 counts and viral load are monitored per standard of care by a local healthcare provider\n* History of allergy or hypersensitivity to study drug components\n* Any positive test result for hepatitis B virus (HBV) indicating presence of virus (e.g., hepatitis B surface antigen \\[HBsAg, Australia antigen\\]) positive\n* Any positive test result for hepatitis C virus (HCV) indicating presence of active viral replication (detectable HCV-ribonucleic acid \\[RNA\\]). Note: Participants with positive HCV antibody and an undetectable HCV RNA are eligible to enroll",{"count":292,"type":20},50,[118],"This phase II trial compares the impact of subcutaneous (SC) nivolumab given in an in-home setting to an in-clinic setting on cancer care and quality of life. Currently, most drug-related cancer care is conducted in clinic type centers or hospitals which may isolate patients from family, friends and familiar surroundings for many hours per day. This separation adds to the physical, emotional, social, and financial burden for patients and their families. Traveling to and from medical facilities costs time, money, and effort and can be a disadvantage to patients living in rural areas, those with low incomes or poor access to transport. Studies have shown that cancer patients often feel more comfortable and secure being cared for in their own home environments. SC nivolumab in-home treatment may be safe, tolerable and\u002For effective when compared to in-clinic treatment and may reduce the burden of cancer and improve the quality of life in cancer patients.",[296,297,298,299,300,126,301,130,302,303,304,305,54,306,307,308,309,310,160,26,311,312,313,173,314,187,190,315,316,242,27],"Advanced Esophageal Squamous Cell Carcinoma","Advanced Renal Cell Carcinoma","Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8","Clinical Stage IIB Cutaneous Melanoma AJCC v8","Clinical Stage IIC Cutaneous Melanoma AJCC v8","Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8","Clinical Stage IV Esophageal Squamous Cell Carcinoma AJCC v8","Esophageal Carcinoma","Gastroesophageal Junction Adenocarcinoma","Hepatocellular Carcinoma","Lung Non-Small Cell Carcinoma","Malignant Solid Neoplasm","Metastatic Colorectal Carcinoma","Metastatic Cutaneous Melanoma","Metastatic Esophageal Squamous Cell Carcinoma","Recurrent Esophageal Squamous Cell Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","Renal Cell Carcinoma","Stage IV Colorectal Cancer AJCC v8","Unresectable Cutaneous Melanoma","Unresectable Esophageal Squamous Cell Carcinoma","2026-06-05",{"date":319,"type":32},"2026-06-09",{"date":321,"type":32},"2024-04-30",{"date":323,"type":20},"2026-12-31",{"name":226,"class":227},{"id":326,"slug":327,"hasResults":11,"nctId":328,"briefTitle":329,"officialTitle":330,"acronym":4,"eligibilityCriteria":331,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":332,"targetDuration":4,"studyType":21,"phases":334,"briefSummary":336,"conditions":337,"keywords":338,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":342,"lastUpdatePostDateStruct":343,"startDateStruct":345,"completionDateStruct":347,"leadSponsor":349,"locationsCount":351},"100582354","phase-4-a-safety-study-of-enfortumab-vedotin-in-indian-adults-with-urothelial-cancer-100582354","NCT06862219","A Safety Study of Enfortumab Vedotin in Indian Adults With Urothelial Cancer","A Multicenter, Phase 4, Open-label, Single-arm, Safety Study of Enfortumab Vedotin in Adult Indian Participants With Previously Treated Locally Advanced or Metastatic Urothelial Cancer","Inclusion Criteria:\n\n* Participant has histologically or cytologically confirmed urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter or urethra). Participants with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible.\n* Participant must have experienced radiographic progression or relapse during or after a checkpoint inhibitor (CPI) (anti-PD-1 or anti-PD-L1) for locally advanced (LA) or metastatic disease. Participants who discontinued CPI treatment due to toxicity are eligible provided that they have evidence of disease progression following discontinuation. The CPI need not be the most recent therapy. Participants for whom the most recent therapy has been a non-CPI based regimen are eligible if they have progressed \u002F relapsed during or after their most recent therapy. LA disease must not be amenable to resection with curative intent.\n* Participant must have received a platinum-containing regimen (cisplatin or carboplatin) in the metastatic \u002F LA, neoadjuvant or adjuvant setting. If platinum was administered in the ajuvant\u002Fneoadjuvant setting, the participant must have progressed within 12 months of completion.\n* Participant must have measurable metastatic or LA disease at baseline according to RECIST version 1.1.\n* Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Participant's baseline laboratory data meets protocol specified of criteria.\n* Female participant is not pregnant and at least 1 of the following conditions apply:\n\n  * Not a woman of childbearing potential (WOCBP)\n  * WOCBP who has a negative urine or serum pregnancy test at screening or within 7 days prior to day 1 and agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after final study intervention administration.\n* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for approximately 6 months after final study intervention administration.\n* Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period and for 6 months after final study intervention administration.\n* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 6 months after final study intervention administration.\n* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after final study intervention administration.\n* Male participant must not donate sperm during the treatment period and for 6 months after final study intervention administration.\n* Participant agrees not to participate in another interventional study while receiving study intervention in the present study.\n\nExclusion Criteria:\n\n* Participant has preexisting sensory or motor neuropathy grade ≥ 2.\n* Participant has active central nervous system (CNS) metastases. Participant with treated CNS metastases is permitted on study if all the following are true:\n\n  * CNS metastases have been clinically stable for at least 6 weeks prior to screening\n  * If requiring steroid treatment for CNS metastases, the participant is on a stable dose ≤ 20 mg\u002Fday of prednisone or equivalent for at least 2 weeks\n  * Baseline scans show no evidence of new or enlarged brain metastasis\n  * Participant does not have leptomeningeal disease\n* Participant has ongoing clinically significant toxicity (grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).\n\n  * Participant with ≤ grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well-maintained \u002F controlled on a stable dose of hormone replacement therapy (HRT) (if indicated).\n  * Participant with ongoing ≥ grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded.\n  * Participant with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or participant with other immunotherapy-related AEs requiring high doses of steroids (\\> 20 mg\u002Fday of prednisone or equivalent) are excluded.\n* Participant has history of another malignancy within 3 years before the first dose of study intervention or any evidence of residual disease from a previously diagnosed malignancy.\n\n  * Participant with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance \u002F watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.\n* Participant with a positive hepatitis B surface antigen and\u002For anti-hepatitis B core antibody and a negative polymerase chain reaction assay at baseline should receive appropriate antiviral prophylaxis or regular surveillance monitoring as per local or institutional guidelines.\n* Participant has active hepatitis C infection or known human immunodeficiency virus infection. Participant who has been treated for hepatitis C infection is permitted if they have documented sustained virologic response of ≥ 12 weeks.\n* Participant has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III to IV within 6 months prior to the first dose of study intervention administration.\n* Participant has known active keratitis or corneal ulcerations. Participant with superficial punctate keratitis is allowed if the disorder is being adequately treated.\n* Participant has other underlying medical condition that would impair the ability of the participant to receive or tolerate the planned treatment and follow-up.\n* Participant has history of uncontrolled diabetes mellitus within 3 months of the first dose of study intervention. Uncontrolled diabetes is defined as HbA1c ≥ 8 percent or HbA1c between 7 percent and \\\u003C 8 percent with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.\n* Participant has prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody drug conjugate (ADCs).\n* Participant is currently receiving systemic antimicrobial treatment for viral, bacterial, or fungal infection at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.\n* Participant has radiotherapy or major surgery within 4 weeks prior to first dose study intervention administration.\n* Participant has had chemotherapy, biologics, investigational agents, and\u002For antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study intervention administration.\n* Participant has any condition which makes the participant unsuitable for study participation.\n* Participant has a known or suspected hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20); OR participant has known hypersensitivity to biopharmaceuticals produced in CHO cells.",{"count":333,"type":20},100,[335],"PHASE4","This study is for Indian adults in India who have cancer in the bladder lining (urothelial cancer). Their cancer is advanced or has spread to other parts of the body. Enfortumab vedotin is a treatment for this type of cancer.\n\nThe main aim of the study is to confirm the safety of enfortumab vedotin in Indian adults with urothelial cancer.\n\nDuring the study, people will receive enfortumab vedotin. The study treatment will be given to people slowly through a tube into a vein. This is called an infusion. People will receive 3 separate infusions of enfortumab vedotin in each 28-day (4 weeks) treatment cycle.\n\nPeople visit their study clinic for health-checks several times during and after they receive enfortumab vedotin.",[26],[339,340,341,246],"PADCEV","ASG-22CE","Urothelial cancer","2026-05-27",{"date":344,"type":32},"2026-05-28",{"date":346,"type":32},"2025-06-21",{"date":348,"type":20},"2027-12-31",{"name":350,"class":104},"Astellas Pharma Global Development, Inc.",13,{"id":353,"slug":354,"hasResults":11,"nctId":355,"briefTitle":356,"officialTitle":357,"acronym":4,"eligibilityCriteria":358,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":359,"targetDuration":4,"studyType":360,"phases":4,"briefSummary":361,"conditions":362,"keywords":364,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":370,"lastUpdatePostDateStruct":371,"startDateStruct":373,"completionDateStruct":375,"leadSponsor":377,"locationsCount":378},"100622976","a-study-of-neuropathy-caused-by-enfortumab-vedotin-in-people-with-urothelial-carcinoma-100622976","NCT07390617","A Study of Neuropathy Caused by Enfortumab Vedotin in People With Urothelial Carcinoma","Interrogating Enfortumab Vedotin-associated Neuropathy in Patients With Metastatic or Muscle-Invasive Urothelial Carcinoma Receiving Enfortumab Vedotin","Inclusion Criteria:\n\n* Written informed consent by and HIPAA authorization for release of personal health information obtained from the research participant.\n* Able to speak and read English to a sufficient level of fluency to provide informed consent and complete the study questionnaires.\n* Age ≥ 18 years at the time of consent.\n* ECOG Performance Status of ≤ 3 within 28 days prior to consent.\n* Histological or cytologically confirmed urothelial carcinoma.\n* Patients must be planned to start systemic therapy with enfortumab vedotin\n* At time of enrollment, patients must be planned to start enfortumab with or without pembrolizumab\n\nExclusion Criteria:\n\nSubjects meeting any of the criteria below may not participate in the study:\n\n* Inability of the subject to understand and comply with study procedures.\n* Having previously received enfortumab vedotin\n* Students\u002Femployees of the study institution, pregnant women, prisoners, and institutionalized individuals (to prevent enrollment of vulnerable subjects).",{"count":292,"type":20},"OBSERVATIONAL","The purpose of this study is to see how results of nerve tests change in people with urothelial cancer who receive treatment with enfortumab vedotin (EV)",[363,242,26],"Neuropathy",[365,366,367,368,369],"urothelial carcinoma","metastatic urothelial carcinoma","neuropathy","Memorial Sloan Kettering Cancer Center","25-371","2026-05-26",{"date":372,"type":32},"2026-05-29",{"date":374,"type":32},"2026-01-20",{"date":376,"type":20},"2028-01-20",{"name":368,"class":227},7,{"id":380,"slug":381,"hasResults":11,"nctId":382,"briefTitle":383,"officialTitle":384,"acronym":4,"eligibilityCriteria":385,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":386,"targetDuration":4,"studyType":21,"phases":387,"briefSummary":388,"conditions":389,"keywords":4,"overallStatus":94,"whyStopped":4,"lastUpdateSubmitDate":405,"lastUpdatePostDateStruct":406,"startDateStruct":408,"completionDateStruct":410,"leadSponsor":412,"locationsCount":105},"100638080","phase-2-low-dose-reduced-frequency-nivolumab-for-the-treatment-of-unresectable-or-metastatic-cancer-afford-io-trial-100638080","NCT07576725","Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial","AFFORD IO: A Phase 2 Trial of Low Dose, Reduced Frequency Nivolumab (Anti-PD-1 Antibody) in Patients With Unresectable or Metastatic Cancer","Inclusion Criteria:\n\n* Participants are eligible if they have one of these histologically confirmed, unresectable or metastatic cancer types listed below, based upon historical responsiveness to anti-PD-(L)1 agents\n\n  * Non-small cell lung cancer (NSCLC) with documented PD-L1 expression (combined positive score \\[CPS\\] ≥ 1) (NOTE: Participants with known driver oncogenic mutations\u002Frearrangements, including EGFR, ALK and ROS-1, will be excluded.)\n  * Head and neck squamous cell carcinoma (HNSCC) with documented PD-L1 expression (CPS ≥ 1)\n  * Clear cell renal cell carcinoma (ccRCC) (NOTE: Other subtypes may be permitted after approval by the Medical Monitor)\n  * Melanoma (cutaneous, acral-lentiginous and mucosal subtypes), and non-melanoma skin cancers, (cutaneous squamous cell carcinoma \\[CSCC\\], basal cell carcinoma \\[BCC\\] and Merkel cell carcinoma \\[MCC\\])\n  * Hodgkin's lymphoma\n  * Urothelial carcinoma\n  * Cervical cancer with documented PD-L1 expression (CPS ≥ 1)\n  * Colorectal cancer with high microsatellite instability (MSI) or mismatch repair deficiency\n  * Kaposi sarcoma (KS) without clinical concern for multicentric Castleman's disease (MCD)\n  * Any cancer type with historical data suggesting an ORR \\> 20% with anti-PD(L)-1 agents (NOTE: All participants in this category must be approved by the Medical Monitor prior to enrollment.)\n* Must have experienced disease progression after or deemed not to be a good candidate for available curative systemic therapy options\n* Presence of at least one measurable tumor, per RECIST v1.1\n* Age 18 or older. (NOTE: Both men and women, and members of all races and ethnic groups are eligible for this trial.)\n* Eastern Cooperative Oncology Group (ECOG) performance score of 0-2\n* Absolute neutrophil count (ANC) ≥ 1.0 × 10\\^9\u002FL\n* Platelet count ≥ 75 × 10\\^9\u002FL\n* Hemoglobin ≥ 9 g\u002FdL (NOTE: Participants may have been transfused)\n* Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) (or total bilirubin ≤ 2.5 × upper limit of normal \\[ULN\\] in participants with Gilbert's syndrome)\n* Estimated creatinine clearance ≥ 30mL\u002Fmin according to the Cockcroft-Gault formula or according to local institutional standard\n* Must consent to undergo serial research blood draws at study defined timepoints, unless deemed unsafe or not feasible by the treating investigator\n* Must have an ability to understand and provide consent to the institutional review board (IRB)-approved informed consent form (ICF) document(s)\n* Women of childbearing potential must have a negative serum or urine pregnancy test at screening\n* Both male and female participants must be willing to use highly effective contraception, as stipulated in national or local guidelines, throughout the study and for at least 180 days after the last treatment administration, if the risk of conception exists\n\nExclusion Criteria:\n\n* Prior exposure to any immune-checkpoint inhibitor for any reason\n* Residual adverse event(s) from prior therapy grade \\> 1 (National Cancer Institute \\[NCI\\]-Common Terminology Criteria for Adverse Events \\[CTCAE\\] v6.0) that could interfere with study endpoints or put participant safety at risk, as determined by the treating investigator\n* Known active central nervous system (CNS) metastases and\u002For prior history of leptomeningeal cancer involvement\n* Known history of another active malignancy (besides the eligible cancer diagnosis) within the last 3 years from day 1 of nivolumab that could interfere with study endpoints or put participant safety at risk. (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ \\[skin, bladder, cervical, colorectal, breast\\] or low grade prostatic intraepithelial neoplasia or grade 1 prostate cancer. Any other neoplasm, which has been treated adequately and is adjudged by the treating investigator to have a low risk of progression during the study, could be enrolled only after approval from the medical monitor.)\n* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as follows:\n\n  * Active HBV is defined as a known positive hepatitis B virus surface antigen (HBsAg) result or positive total hepatitis B virus core antibody (anti-HBc) results in the absence of hepatitis B virus surface antibody (anti-HBsAb). (NOTE: When HBsAg is negative and HBcAb is positive, HBV-DNA should be measured. When HBV-deoxyribonucleic acid \\[DNA\\] is negative, this participant could be enrolled with close monitoring of HBV activities.)\n  * Active hepatitis C virus (HCV) is defined as a known positive HCV antibody result and quantitative HCV-ribonucleic acid (RNA) results greater than the lower limits of detection of the assay. (NOTE: Participants who have had definitive treatment for HCV are permitted if HCV-RNA is undetectable.)\n* Known uncontrolled HIV infection. (NOTE: HIV-infected participants may be allowed if all the following criteria are met: CD4 count ≥ 100\u002FμL, viral load less than 200 copies\u002FmL, and clinically stable on antiretroviral therapy \\[ART\\] for at least 3 months.)\n\n  * These participants will be enrolled only after approval from the medical monitor\n* Known active autoimmune disease or an allograft requiring systemic immunosuppression with corticosteroids (\\> 10 mg\u002Fday of prednisone or equivalent) or immunosuppressive drugs within the past 2 years before the first dose of nivolumab. (NOTE: Exceptions will be made for participants with autoimmune conditions such as diabetes type I, vitiligo, psoriasis, hypothyroid or hyperthyroid diseases not requiring immunosuppressive treatment; participants receiving physiologic corticosteroid replacement therapy at doses \\\u003C 10 mg\u002Fday of prednisone or equivalent for adrenal or pituitary insufficiency; participants with a condition such as asthma or chronic obstructive pulmonary disease that requires intermittent use of steroids or those who require brief courses of corticosteroids for prophylaxis \\[e.g., contrast dye allergy\\], nivolumab-related standard premedication, and\u002For treatment of non-serious immune related adverse events. Any other situation must be discussed with the medical monitor for risk\u002Fbenefit assessment.)\n* Immunosuppressed status due to severe uncontrolled diabetes, concurrent uncontrolled hematological malignancy, or other comorbidities\n* Known history of serious, active infections (aside from well-controlled HIV, as per exclusion criterion #6) requiring systemic antimicrobial agents within 14 days before the first dose of nivolumab. (NOTE: Chronic infections such as herpes simplex virus requiring suppressive therapy may be allowed after discussion with the medical monitor for risk\u002Fbenefit assessment.)\n* Known history of clinically significant interstitial lung disease, or active noninfectious pneumonitis\n* Clinically significant (i.e., active) cardiovascular disease such as cerebral vascular accident or myocardial infarction within 6 months prior to first dose of nivolumab, ongoing unstable angina or congestive heart failure (New York Heart Association Classification class II-IV), or serious cardiac arrhythmia that could jeopardize participant safety on the study\n* Receipt of live vaccine(s) within 30 days of planned start of nivolumab. (NOTE: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster \\[chickenpox\\], yellow fever, rabies, bacillus Calmette Guerin \\[BCG\\], and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.)\n* Known severe acute or chronic medical conditions such as uncontrolled seizure disorder, serious psychiatric illness, or laboratory abnormalities, that may increase the risk associated with study participation or may interfere with the interpretation of study endpoints and, in the judgment of the treating investigator, would make the participant inappropriate for entry into this study\n* Known active tuberculosis (TB). (NOTE: Participants with latent TB will be allowed, provided they are receiving tuberculosis preventive therapy, after approval of the medical monitor.)\n* Known allergy or hypersensitivity to any component of the study drug formulation (including excipients and additives) that could interfere with study endpoints or put participant safety at risk\n* Pregnant or breast-feeding woman",{"count":292,"type":20},[118],"This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab is a type of immune checkpoint inhibitor (ICI). ICIs have revolutionized the treatment of numerous cancers with remarkable improvement in participant outcomes. However, accessibility of ICIs is extremely poor on a global scale, mainly due to high costs. Previous research has suggested that these drugs can be given at lower doses and reduced frequency than their approved dosing regimens, with similar results. Giving nivolumab at a lower dose and less often may help reduce the cost of therapy, improve immunotherapy accessibility, and therefore improve survival outcomes globally.",[126,390,130,391,392,393,394,395,156,396,308,309,160,397,162,163,165,398,167,26,170,399,216,172,173,186,314,217,189,190,400,401,200,402,403,315,204,206,207,209,404,211,27],"Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8","Hodgkin Lymphoma","Kaposi Sarcoma","Metastatic Acral Lentiginous Melanoma","Metastatic Basal Cell Carcinoma","Metastatic Clear Cell Renal Cell Carcinoma","Metastatic Kaposi Sarcoma","Metastatic Mucosal Melanoma","Stage III Colorectal Cancer AJCC v8","Unresectable Acral Lentiginous Melanoma","Unresectable Basal Cell Carcinoma","Unresectable Clear Cell Renal Cell Carcinoma","Unresectable Colorectal Carcinoma","Unresectable Mucosal Melanoma","2026-05-01",{"date":407,"type":32},"2026-05-08",{"date":409,"type":20},"2026-09-01",{"date":411,"type":20},"2029-08-31",{"name":413,"class":227},"Fred Hutchinson Cancer Center",{"id":415,"slug":416,"hasResults":11,"nctId":417,"briefTitle":418,"officialTitle":419,"acronym":4,"eligibilityCriteria":420,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":421,"targetDuration":4,"studyType":21,"phases":423,"briefSummary":424,"conditions":425,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":427,"lastUpdatePostDateStruct":428,"startDateStruct":430,"completionDateStruct":432,"leadSponsor":434,"locationsCount":105},"100429896","phase-1-cabozantinib-in-combination-with-enfortumab-vedotin-for-locally-advanced-or-metastatic-urothelial-cancer-100429896","NCT04878029","Cabozantinib in Combination With Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Cancer","A Phase I\u002FIb Open Label, Single-Arm Study of Cabozantinib in Combination With Enfortumab Vedotin (EV) in the Treatment of Locally Advanced or Metastatic Urothelial Cancer","Inclusion Criteria:\n\n* Histologically-documented urothelial carcinoma (squamous differentiation or mixed cell types allowed if urothelial carcinoma is present)\n* Metastatic disease or unresectable locally-advanced disease\n* Must have received prior treatment with a checkpoint inhibitor (CPI). A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor alone or with any other combination\n* Must either have prior treatment with platinum-containing chemotherapy or be ineligible at time of enrollment\n* Recovery to baseline or =\\\u003C grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and\u002For stable on supportive therapy\n* Tumor tissue samples must be available for submission prior to initiation of study treatment or patient must be willing to undergo repeat tumor biopsy\n* Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1)\n* An Eastern Cooperative Oncology Group (ECOG) performance status score of =\\\u003C 2\n* Must be \\>= 18 years of age\n* Absolute neutrophil count (ANC) \\>= 1500\u002FuL without granulocyte colony-stimulating factor support (within 28 days before first dose of study treatment)\n* White blood cell count \\>= 2500\u002FuL (within 28 days before first dose of study treatment)\n* Platelets \\>= 100,000\u002FuL without transfusion (within 28 days before first dose of study treatment)\n* Hemoglobin \\>= 9 g\u002FdL (within 28 days before first dose of study treatment)\n* Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) =\\\u003C 3 x upper limit of normal (ULN). ALP =\\\u003C 5 x ULN with documented bone metastases (within 28 days before first dose of study treatment)\n* Total bilirubin =\\\u003C 1.5 x ULN (for subjects with Gilbert's disease =\\\u003C 3 x ULN) (within 28 days before first dose of study treatment)\n* Prothrombin (PT)\u002Finternational normalized ratio (INR) or partial thromboplastin time (PTT) test \\\u003C 1.3 x the laboratory ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants (within 28 days before first dose of study treatment)\n* Calculated creatinine clearance \\>= 30 mL\u002Fmin (\\>= 0.5 mL\u002Fsec) using the Cockcroft-Gault equation (within 28 days before first dose of study treatment)\n* Urine protein\u002Fcreatinine ratio (UPCR) =\\\u003C 1 mg\u002Fmg (=\\\u003C 113.2 mg\u002Fmmol), or 24-hour (h) urine protein =\\\u003C 1 g (within 28 days before first dose of study treatment)\n* Capable of understanding and complying with the protocol requirements and must have signed the informed consent document\n* Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment\n* Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \\> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \\\u003C 55 years-of-age must have a serum follicle stimulating (FSH) level \\> 40 mIU\u002FmL to confirm menopause). Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site\n\nExclusion Criteria:\n\n* Prior treatment with cabozantinib\n* Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs)\n* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment\n* Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks before first dose of study treatment\n* Radiation therapy within 2 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment\n* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment\n* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:\n\n  * Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).\n  * Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor\n* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n  * Cardiovascular disorders:\n\n    * Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.\n    * Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment.\n    * Stroke (including transient ischemic attack \\[TIA\\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment\n\n      * Subjects with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep venous thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation for at least 1 week before first dose of study treatment\n  * Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\n\n    * The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.\n    * Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.\n    * Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment\n* Clinically significant hematuria, hematemesis, or hemoptysis of \\> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment\n* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation\n* Lesions invading or encasing any major blood vessels\n* Ongoing sensory or motor neuropathy grade \\>= 2\n* Other clinically significant disorders that would preclude safe study participation.\n\n  * Serious non-healing wound\u002Fulcer\u002Fbone fracture.\n  * Uncompensated\u002Fsymptomatic hypothyroidism.\n  * Moderate to severe hepatic impairment (Child-Pugh B or C).\n  * Uncontrolled diabetes mellitus defined as a hemoglobin A1C \\>= 8%\n* Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible\n* Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment. Note: If a single ECG shows a QTcF with an absolute value \\> 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility\n* Pregnant or lactating females\n* Inability to swallow tablets\n* Previously identified allergy or hypersensitivity to components of the study treatment formulations\n* Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or prostate, cervix, or breast",{"count":422,"type":20},32,[23],"This phase I\u002FIb trial seeks to find out the best dose, possible benefits and\u002For side effects of cabozantinib in combination with enfortumab vedotin in treating urothelial cancer that has spread to nearby tissues and lymph nodes (locally advanced) or other parts of the body (metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to a toxic agent called vedotin. Enfortumab attaches to nectin-4 tumor cells in a targeted way and delivers vedotin to kill them. Cabozantinib in combination with enfortumab vedotin may be safe and effective in treating locally advanced or metastatic urothelial cancer.",[426,54,26,27],"Infiltrating Bladder Urothelial Carcinoma With Squamous Differentiation","2026-04-23",{"date":429,"type":32},"2026-04-29",{"date":431,"type":32},"2021-07-23",{"date":433,"type":20},"2028-12-21",{"name":435,"class":227},"Emory University",{"id":437,"slug":438,"hasResults":11,"nctId":439,"briefTitle":440,"officialTitle":441,"acronym":4,"eligibilityCriteria":442,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":443,"targetDuration":4,"studyType":21,"phases":444,"briefSummary":446,"conditions":447,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":459,"lastUpdatePostDateStruct":460,"startDateStruct":462,"completionDateStruct":464,"leadSponsor":466,"locationsCount":105},"100415725","cryoablation-combined-with-stereotactic-body-radiation-therapy-for-the-treatment-of-painful-bone-metastases-the-crome-trial-100415725","NCT04693377","Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial","Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases","Inclusion Criteria:\n\n* Patient must have a primary diagnosis of malignancy and radiographic evidence of bone metastases. Eligible tumor histologies include the following malignancies with low alpha\u002Fbeta ratios: renal cell carcinoma, urothelial carcinomas, castration-resistant prostate cancer, sarcoma, thyroid carcinoma, colorectal carcinoma, and melanoma\n* A target lesion the meets the following criteria:\n\n  * The target lesion must be amenable to both cryoablation and SBRT, as determined by the study principal investigators (PIs)\n  * The target lesion must be =\\\u003C 7cm\n  * The pain due to the target lesion must be at least 4\u002F10 based on the BPI pain scale\n  * Pain from the metastatic site must correlate with an identifiable tumor on computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US) imaging\n* Life expectancy \\>= 3 months\n* Platelet count \\> 50,000\u002Fmm\\^3 within 6 weeks of screening\n* International normalized ratio (INR) \\\u003C 1.5 within 6 weeks of screening\n* If taking antiplatelet or anticoagulation medication, it must be able to be discontinued 48 hours prior to the procedure or at the discretion of the PI (e.g., aspirin, ibuprofen, low molecular weight heparin \\[LMWH\\] preparations)\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 1 (Karnofsky \\>= 70%) within 6 weeks of screening\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: 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. 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\n* All lines of prior systemic therapy are permissible. Standard concurrent chemotherapy, immunotherapy, or targeted therapy are permissible\n* Ability to understand and the willingness to sign a written informed consent document\n\nExclusion Criteria:\n\n* Prior locoregional therapy to target lesion, including ablation of any modality, embolization, radiation, or surgery\n* Patient may not be receiving any other investigational agents. Standard concurrent chemotherapy, immunotherapy, or targeted therapy will be allowed\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant or nursing women; women of childbearing potential unless using effective contraception as determined by the investigator\n* Target lesions that involve the spinal column or calvarium\n* Absolute neutrophil count \\\u003C 1000 mm\\^3 within 6 weeks of screening\n* Active infection\n* Presence of confirmed pathologic fracture at the target lesion not amenable to percutaneous stabilization\n* Lesions that involve a weight-bearing long bone of the lower extremity with the tumor causing \\> 50% loss of cortical bone. Lesions involving the hands and feet",{"count":72,"type":20},[445],"NA","This trial compares cryoablation combined with stereotactic body radiation therapy to stereotactic body radiation therapy alone to see how well they work in treating patients with pain from cancer that has spread to the bones (bone metastases). Bone is a common site of metastasis in advanced cancer, and bone metastases often result in debilitating cancer-related pain. The current standard of care to treat painful bone metastases is radiation therapy alone. However, many patients do not get adequate pain relief from radiation therapy alone. Another type of therapy that may be used to provide pain relief from bone metastases is cryoablation. Cryoablation is a procedure in which special needles are inserted into the tumor site. These needles grow ice balls at their tips to freeze and kill cancer cells. The goal of this trial is to compare how well cryoablation in combination with radiation therapy works to radiation therapy alone when given to cancer patients to provide pain relief from bone metastases.",[448,308,449,163,164,450,166,451,452,26,314,453,190,454,455,456,457,458],"Castration-Resistant Prostate Carcinoma","Metastatic Malignant Neoplasm in the Bone","Metastatic Prostate Carcinoma","Metastatic Sarcoma","Metastatic Thyroid Gland Carcinoma","Stage IV Prostate Cancer AJCC v8","Stage IVA Colorectal Cancer AJCC v8","Stage IVA Prostate Cancer AJCC v8","Stage IVB Colorectal Cancer AJCC v8","Stage IVB Prostate Cancer AJCC v8","Stage IVC Colorectal Cancer AJCC v8","2026-04-10",{"date":461,"type":32},"2026-04-15",{"date":463,"type":32},"2021-03-16",{"date":465,"type":20},"2027-04-01",{"name":467,"class":227},"M.D. Anderson Cancer Center",{"id":469,"slug":470,"hasResults":11,"nctId":471,"briefTitle":472,"officialTitle":473,"acronym":474,"eligibilityCriteria":475,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":476,"enrollmentInfo":477,"targetDuration":4,"studyType":21,"phases":479,"briefSummary":480,"conditions":481,"keywords":483,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":495,"lastUpdatePostDateStruct":496,"startDateStruct":498,"completionDateStruct":500,"leadSponsor":502,"locationsCount":105},"100630819","phase-1-dual-target-nectin-4her2-car-nk-cells-in-advanced-urothelial-carcinoma-100630819","NCT07492628","Dual-Target Nectin-4\u002FHER2 CAR-NK Cells in Advanced Urothelial Carcinoma","A Phase 1, Open-Label, Multicenter, Non-Randomized, Dose-Escalation and Dose-Expansion Study of Allogeneic Dual-Target Nectin-4\u002FHER2 CAR-NK Cells Following Fludarabine\u002FCyclophosphamide Lymphodepletion in Adults With Relapsed\u002FRefractory, Locally Advanced or Metastatic Urothelial Carcinoma","DUET-UC-NK","Inclusion Criteria:\n\n* Age 18-75 years at consent.\n* Histologically confirmed urothelial carcinoma of the bladder, ureter, renal pelvis, or urethra that is unresectable locally advanced or metastatic.\n* Disease progression after, intolerance to, or ineligibility for standard therapy, including platinum-based chemotherapy and PD-1\u002FPD-L1 blockade when appropriate for the patient and region. Prior enfortumab vedotin and prior HER2-directed therapy are allowed, but a fresh biopsy is strongly preferred after the latest systemic regimen.\n* At least one measurable lesion per RECIST v1.1.\n* Tumor tissue available for central review demonstrating Nectin-4 positivity (for example, IHC ≥1+ in ≥10% tumor cells) and HER2 status assessed by IHC\u002FISH. At least one of the selected therapeutic targets must be present; dose expansion preferentially enrolls Nectin-4-positive disease.\n* ECOG performance status 0-1.\n* Adequate bone marrow, hepatic, renal, and coagulation function.\n* Life expectancy of at least 12 weeks.\n* Negative pregnancy test for women of childbearing potential and agreement to use highly effective contraception during study treatment and follow-up as defined in the protocol.\n* Ability to understand and sign informed consent.\n\nExclusion Criteria:\n\n* Active or untreated central nervous system metastases or leptomeningeal disease. Previously treated CNS disease is allowed if clinically stable and off escalating corticosteroids.\n* Prior allogeneic hematopoietic stem cell transplant, prior solid-organ transplant, or active graft-versus-host disease.\n* Clinically significant autoimmune disease requiring systemic immunosuppression within the defined washout window.\n* Uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, sepsis, or active tuberculosis.\n* Clinically significant cardiac disease, active myocarditis, unstable angina, recent myocardial infarction, uncontrolled arrhythmia, or clinically meaningful decline in left ventricular ejection fraction that would increase risk from HER2-directed cell therapy.\n* Clinically significant pulmonary disease (for example, uncontrolled interstitial lung disease or oxygen-dependent respiratory compromise).\n* Use of systemic corticosteroids or other immunosuppressive medications above protocol-allowed limits within the washout window.\n* History of severe hypersensitivity to fludarabine, cyclophosphamide, or cell-product excipients.\n* Pregnancy or breastfeeding.\n* Another active malignancy requiring systemic therapy or likely to interfere with protocol assessments, except for protocol-allowed low-risk cancers.","75 Years",{"count":478,"type":20},42,[23],"This hypothetical first-in-human study is designed to evaluate the safety, feasibility, and preliminary anti-tumor activity of an allogeneic dual-target Nectin-4\u002FHER2 CAR-NK cell product in adults with relapsed\u002Frefractory locally advanced or metastatic urothelial carcinoma. Based on public urothelial-cancer evidence, Nectin-4 was selected as the lead antigen because it has the strongest disease-specific clinical validation; HER2\u002FERBB2 was chosen as the secondary co-target to broaden tumor coverage and reduce antigen-escape risk. EpCAM is not selected as a therapeutic co-target in this example because of broader normal epithelial expression and weaker tumor specificity in urothelial carcinoma.",[241,242,26,54,482],"Upper Tract Urothelial Carcinoma",[484,485,486,487,488,365,489,490,491,492,493,494],"CAR-NK","allogeneic NK cells","Nectin-4","HER2","ERBB2","bladder cancer","dual-target","lymphodepletion","solid tumor immunotherapy","EpCAM","RP2D","2026-03-20",{"date":497,"type":32},"2026-03-25",{"date":499,"type":32},"2026-03-02",{"date":501,"type":20},"2028-05-17",{"name":503,"class":104},"Beijing Biotech",{"id":505,"slug":506,"hasResults":11,"nctId":507,"briefTitle":508,"officialTitle":509,"acronym":510,"eligibilityCriteria":511,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":512,"targetDuration":4,"studyType":21,"phases":514,"briefSummary":515,"conditions":516,"keywords":518,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":520,"lastUpdatePostDateStruct":521,"startDateStruct":523,"completionDateStruct":525,"leadSponsor":527,"locationsCount":105},"100610004","phase-2-pembrolizumab-maintenance-after-enfortumab-vedotin-evpembro-induction-in-front-line-metastatic-urothelial-carcinoma-100610004","NCT07221942","Pembrolizumab Maintenance After Enfortumab Vedotin (EV)\u002FPembro Induction in Front-Line Metastatic Urothelial Carcinoma","Pembrolizumab Maintenance After Enfortumab Vedotin\u002FPembrolizumab Induction in Front-Line Metastatic Urothelial Carcinoma","IMPROEV","Inclusion Criteria:\n\n* Patients must have histologically and radiographically confirmed locally advanced, unresectable urothelial carcinoma.\n* Patients should not have received prior systemic therapy for metastatic disease.\n* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1\n* Patients may have received prior neoadjuvant or adjuvant immune checkpoint inhibitor therapy for localized disease and are eligible if they completed the treatment ≥12 months prior to initiating treatment on this clinical trial.\n* ECOG performance status 0-2\n* Ability to understand and willingness to sign a written informed consent and HIPAA consent document\n* Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin fixed, paraffin embedded (FFPE) tissue block(s) or at least 25 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.\n* Normal organ and marrow function as defined below.\n\n  * Absolute neutrophil count \\> 1,000\u002Fmm3 unless patient has constitutional neutropenia\n  * Platelets \\> 100,000\u002Fµl\n  * Hemoglobin \\> 8.0 g\u002FdL\n  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C2.5 x upper limit of normal (ULN) or \\\u003C3.5 x ULN if liver metastases\n  * Creatinine Clearance \\>20 ml\u002Fmin\n\nExclusion Criteria:\n\n* Patients who have received prior monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs) for urothelial cancer.\n* Grade 2 or higher baseline sensory or motor neuropathy.\n* Uncontrolled diabetes (HbA1c \\>8%)\n* Patients with uncontrolled and untreated central nervous system (CNS) metastases.\n\n  * Prior radiation to CNS metastases is permitted.\n  * Prior history of CNS disease that has responded to previous systemic therapy is permitted only if no recurrence.\n  * Patient should not have leptomeningeal disease\n  * CNS metastases have been clinically stable for at least 6 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis.\n  * If requiring steroid treatment for CNS metastases, the patient is on stable dose \\\u003C 10 mg\u002Fday of prednisone or equivalent for at least 2 weeks prior to starting treatment\n* Uncontrolled intercurrent illness including, but not limited to ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic uncontrolled cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that, in the opinion of the investigator, would substantially impair the patient's ability to comply with study requirements. Efforts should be made to provide reasonable accommodations before determining exclusion based on social limitations.\n* Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug that cannot be watched and requires treatment, or any evidence of residual disease from a previously diagnosed malignancy that cannot be watched and requires treatment. Adjuvant hormonal therapy for breast cancer is allowed.\n* Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.\n* Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with enfortumab vedotin.\n* History of idiopathic pulmonary fibrosis; organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.\n* Prior allogeneic stem cell or solid organ transplant.\n* Other underlying medical condition that, in the opinion of the investigator, would impair the ability of the patient to receive or tolerate the planned treatment and follow-up; any known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.\n* Patients with active tuberculosis.\n* Pregnant or breast feeding\n* History of autoimmune diseases. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease modifying agents, corticosteroids, or immunosuppressive drugs).\n\n  * Patients with vitiligo or residual autoimmune hypothyroidism on stable doses of hormone replacement are permitted to enroll.\n  * Patients with type 1 diabetes mellitus (T1DM) on a stable dose of insulin are permitted to enroll.\n  * Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.\n* On high dose steroids at the time of study enrollment, defined as \\>10 mg prednisone (or bioequivalent), including steroids used for management of intracranial lesions. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.\n* Patients who received prior immunotherapy for mUC or for an alternative malignancy are eligible unless they developed an immune related adverse event while on therapy requiring cessation of therapy or use of disease modifying agents, corticosteroids, or immunosuppressive drugs.",{"count":513,"type":20},97,[118],"This is a single-arm, open-label, non-randomized Phase II trial evaluating the efficacy of induction therapy with enfortumab vedotin (EV) plus pembrolizumab (P) for 18 weeks (6 cycles), followed by maintenance pembrolizumab in treatment-naïve patients with metastatic urothelial carcinoma (mUC). Approximately 97 patients will be enrolled. Induction consists of EV (1.25 mg\u002Fkg IV on Days 1 and 8 of each 21-day cycle; starting dose of 1 mg\u002Fkg allowed) and P (200 mg IV on Day 1 of each cycle). Radiographic assessments occur after 3 and 6 cycles. Patients achieving complete or partial response transition to maintenance P (400 mg IV every 6 weeks or 200 mg IV every 3 weeks) for up to 2 years. Dose modifications for EV are permitted per protocol; no dose adjustments for P. Treatment continues until disease progression, unacceptable toxicity, or completion of maintenance therapy. Patients will enter long-term or survival follow-up as applicable.",[26,27,517],"Advanced Urothelial Carcinoma",[519],"Urothelial carcinoma","2026-02-17",{"date":522,"type":32},"2026-02-19",{"date":524,"type":32},"2026-01-23",{"date":526,"type":20},"2029-09-03",{"name":528,"class":227},"Fox Chase Cancer Center",{"id":530,"slug":531,"hasResults":11,"nctId":532,"briefTitle":533,"officialTitle":533,"acronym":4,"eligibilityCriteria":534,"healthyVolunteers":535,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":536,"targetDuration":4,"studyType":21,"phases":538,"briefSummary":539,"conditions":540,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":550,"lastUpdatePostDateStruct":551,"startDateStruct":553,"completionDateStruct":555,"leadSponsor":557,"locationsCount":105},"100410361","an-investigation-of-kidney-and-urothelial-tumor-metabolism-in-patients-undergoing-surgical-resection-andor-biopsy-100410361","NCT04623502","An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and\u002For Biopsy","Inclusion Criteria:\n\n* Patients must have radiographic evidence of known or probable kidney or urothelial cancer requiring surgical biopsy or excision.\n* Age ≥ 18 years\n* Subjects of all races and ethnic origins\n* The willingness to sign and ability to understand a written informed consent.\n* Patients participating in other clinical trials are eligible, and will be evaluated on a case by case basis by the Principal Investigator, Dr. Vitaly Margulis, MD.\n\nExclusion Criteria:\n\n* Uncontrolled or poorly controlled diabetes for patients receiving a 13C infusion\n* Pregnant or breastfeeding\n* Not a surgical candidate",true,{"count":537,"type":20},600,[445],"The purpose of this study is to understand the metabolism of cancers involving the kidney, including renal cell carcinomas and urothelial cell carcinomas, and how kidney cancers use different types of fuel to support tumor growth. This study uses specially labeled nutrient tracers of compounds normally found circulating in the blood. The nutrients (glucose, fructose, glutamine, acetate, and lactate) are also found in common foods. A nutrient tracer will be given to the participants through an intravenous (IV) catheter during surgery or biopsy, and blood will be collected every 30 minutes during the infusion to monitor safety parameters and the nutrient tracers. The investigators will collect a tissue sample after the completion of surgery. Participants not having an infusion will have their tissue collected after surgery or biopsy.\n\nParticipation in this study will not change patient care. All patients will receive standard of care treatment as determined by their doctors.",[541,313,542,242,543,26,544,545,546,547,548,549],"Kidney Cancer","Clear Cell Carcinoma","Metastatic Kidney Cancer","Papillary Renal Cell Carcinoma","Chromophobe Renal Cell Carcinoma","Fumarate Hydratase Deficiency","Succinate Dehydrogenase-Deficient Renal Cell Carcinoma","HLRCC","Hereditary Leiomyomatosis and Renal Cell Cancer","2026-01-27",{"date":552,"type":32},"2026-01-28",{"date":554,"type":32},"2019-09-30",{"date":556,"type":20},"2027-09-30",{"name":558,"class":227},"University of Texas Southwestern Medical Center",{"id":560,"slug":561,"hasResults":11,"nctId":562,"briefTitle":563,"officialTitle":564,"acronym":565,"eligibilityCriteria":566,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":567,"targetDuration":4,"studyType":360,"phases":4,"briefSummary":568,"conditions":569,"keywords":570,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":571,"lastUpdatePostDateStruct":572,"startDateStruct":574,"completionDateStruct":576,"leadSponsor":578,"locationsCount":105},"100619073","criteria-for-selecting-first-line-metastatic-treatment-for-patients-with-urothelial-carcinoma-100619073","NCT07339878","Criteria for Selecting First-line Metastatic Treatment for Patients With Urothelial Carcinoma","Criteria for Selecting First-line Metastatic Treatment for Patients With Urothelial Carcinoma: Observational, Multicenter, Real-world Study","FLORAL","Inclusion Criteria:\n\n* Patients over 18 years of age\n* Metastatic urothelial carcinoma\n* Treated with first-line metastatic therapy since October 2024\n\nExclusion Criteria:\n\n* Patient who expressed opposition to participating in the study",{"count":292,"type":20},"The standard first-line treatment for metastatic urothelial carcinoma has become the combination of Enfortumab Vedotin and Pembrolizumab following the publication of the EV-302 study results at the end of 2024. Another standard remains in 2025 for patients who are not eligible for the EV Pembrolizumab combination, namely platinum-based chemotherapy +\u002F- avelumab in cases of non-progression. The objective of the FLORAL study is to determine the characteristics of these patients and the reasons that led clinicians to prefer a first-line treatment based on platinum salts.",[26],[242,246,272],"2026-01-05",{"date":573,"type":32},"2026-01-14",{"date":575,"type":32},"2025-04-20",{"date":577,"type":20},"2026-04-20",{"name":579,"class":227},"University Hospital, Strasbourg, France",{"id":581,"slug":582,"hasResults":11,"nctId":583,"briefTitle":584,"officialTitle":585,"acronym":4,"eligibilityCriteria":586,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":587,"targetDuration":4,"studyType":21,"phases":589,"briefSummary":590,"conditions":591,"keywords":594,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":595,"lastUpdatePostDateStruct":596,"startDateStruct":598,"completionDateStruct":600,"leadSponsor":602,"locationsCount":105},"100418077","phase-1-sacituzumab-govitecan-plus-ev-in-metastatic-uc-100418077","NCT04724018","Sacituzumab Govitecan Plus EV in Metastatic UC","Combinations of Sacituzumab Govitecan Plus Enfortumab Vedotin and Pembrolizumab for Metastatic Urothelial Carcinoma: the Double Antibody Drug Conjugate (DAD) and Double Antibody Drug Conjugate With Immunotherapy (DAD-IO) Phase I\u002FII Trial","Phase II Study Cohort A (dose expansion study to assess efficacy of Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) combination)\n\nInclusion Criteria:\n\n* Participants must have histologically documented confirmed predominant urothelial carcinoma (i.e. of the bladder, renal pelvis, ureter or urethra). Patients with squamous differentiation or mixed cell types are eligible if the urothelial component is more than 50%; small-cell carcinoma is not allowed. Patients with locally advanced unresectable disease are eligible.\n* Patient who are cisplatin eligible must have received prior treatment with platinum containing therapy defined as within the adjuvant\u002Fneoadjuvant setting with ≥ ypT2 disease at surgery or recurrent or progressive disease within 12 months or receiving treatment with platinum in locally advanced or metastatic setting. In addition, they must have received a checkpoint inhibitor (CPI) in locally advanced or metastatic urothelial cancer setting. Patients who received CPI therapy in the neoadjuvant\u002Fadjuvant setting and had recurrent or progressive disease either during or within 12 months of therapy completion are eligible. A CPI is defined as a PD-1 or PD-L1 inhibitor.\n* Patients who are cisplatin-ineligible need only have progressed on or since one line of therapy defined as therapy given in the adjuvant\u002Fneoadjuvant setting within 12 months of progression or receiving therapy for locally advanced or metastatic disease\n* Patient must be progressing on or since most recent therapy\n* Age ≥18 years. Children are excluded from this study, but will be eligible for future pediatric trials.\n* ECOG performance status 0-1.\n* Participants must have adequate organ and marrow function as defined below:\n* Leukocytes ≥3,000\u002FmcL\n* Absolute neutrophil count ≥1,500\u002FmcL\n* Platelets ≥100,000\u002FmcL\n* Total bilirubin ≤ institutional upper limit of normal (ULN)\n* AST(SGOT)\u002FALT(SGPT) ≤2.5x institutional ULN OR\n* ≤5x ULN with liver metastases and serum albumin \\> 3 g\u002FdL\n* Glomerular filtration rate (GFR) ≥30 mL\u002Fmin\u002F1.73 m2 (by Cockcroft Gault formula)\n* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Participants 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, participants should be class 2B or better.\n* Have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1 criteria). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \\>2 years\n* The effects of SG and EV on the developing human fetus are unknown. 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 and for the duration of study participation and 6 months after last study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study and up to 6 months after last study drug dose, 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 4 months after completion of SG administration.\n* Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\nSubjects meeting any of the following exclusion criteria at Screening\u002FDay 1 of treatment will not be enrolled in the study.\n\n* Women who are pregnant or lactating. Pregnant women are excluded from this study because SG and EV have 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 EV or SG, breastfeeding should be discontinued if the mother is treated on protocol.\n* Have had a prior anti-cancer biologic agent (including immune checkpoint inhibitors) within 4 weeks prior to Cycle 1 Day 1 (C1D1) or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Subjects participating in observational studies are eligible.\n* Presence of any toxicities attributed to prior anti-cancer therapy that are not resolved to Grade 1 or baseline that could impose serious risk for complications before administration of study drug agent\n* Note: If subjects received major surgery, they must have recovered adequately from the toxicity and\u002For complications from the intervention prior to starting therapy.\n* Have previously received topoisomerase 1 inhibitors, SG or EV\n* Have an active second malignancy. Subjects with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to start of therapy on trial (Cycle 1 Day 1 \\[C1D1\\]), or subjects with surgically-cured tumors with low risk of recurrence are allowed to enroll.\n* Have known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking ≤20 mg\u002Fday of prednisone or its equivalent. All subjects with carcinomatous meningitis are excluded regardless of clinical stability.\n* Have active cardiac disease, defined as:\n* Myocardial infarction or unstable angina pectoris within 6 months prior to C1D1\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation\n* New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of \\\u003C 40%\n* Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of C1D1\n* Have active serious infection requiring antibiotics (Contact sponsor-investigator for clarification)\n* Have other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.\n* Patients with conditions requiring high doses of steroids (\\>10 mg\u002Fday of prednisone or equivalent) or other immunosuppressive medications are excluded. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.\n* History of idiopathic pulmonary fibrosis; organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.\n* Participants who are receiving any other investigational agents.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to EV or SG or any excipient contained in the drug formulations (including 2 (N morpholino) ethane sulfonic acid (MES), histidine, treahalose dihydrate polysorbate 80 and polysorbate 20).\n* Participants with uncontrolled intercurrent illness.\n* Participants with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1C \\>8% or 7-8% with associated diabetes symptoms that are otherwise not explained\n* Uncontrolled tumor related bone pain or impending spinal cord compression.\n\nPhase II Study Cohort B (assessing Sacituzumab Govitecan (SG) + Enfortumab vedotin-ejfv (EV) + Pembrolizumab combination)\n\nInclusion Criteria:\n\n* Participants must have histologically documented confirmed predominant urothelial carcinoma (i.e. of the bladder, renal pelvis, ureter or urethra). Patients with squamous differentiation or mixed cell types are eligible if the transitional component is more than 50%; small-cell carcinoma is not allowed. Patients with locally advanced unresectable disease are eligible.\n* No prior therapy for metastatic urothelial carcinoma. Therapy in the perioperative setting is allowed with no time restrictions on platinum dosing. Prior immunotherapy is allowed provided it has been \\> 6 months from last dose of immune checkpoint blockade.\n* Age ≥18 years; children are excluded from this study, but will be eligible for future pediatric trials.\n* ECOG performance status 0-1.\n* Participants must have adequate organ and marrow function as defined below:\n* Leukocytes ≥3,000\u002FmcL\n* Absolute neutrophil count ≥1,500\u002FmcL\n* Platelets ≥100,000\u002FmcL\n* Total bilirubin ≤ institutional upper limit of normal (ULN)\n* AST(SGOT)\u002FALT(SGPT) ≤2.5x institutional ULN OR\n* ≤5x ULN with liver metastases and serum albumin \\> 3 g\u002FdL\n* Glomerular filtration rate (GFR) ≥30 mL\u002Fmin\u002F1.73 m2 (by Cockcroft Gault formula)\n* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Participants 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, participants should be class 2B or better.\n* Have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1 criteria). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \\>2 years\n* The effects of Pembrolizumab, SG and EV on the developing human fetus are unknown. 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 and for the duration of study participation and 6 months after last study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study and up to 6 months after last study drug dose, 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 4 months after completion of SG administration.\n* Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\nSubjects meeting any of the following exclusion criteria at Screening\u002FDay 1 of treatment will not be enrolled in the study.\n\n* Women who are pregnant or lactating. Pregnant women are excluded from this study because SG and EV have 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 EV or SG, breastfeeding should be discontinued if the mother is treated on protocol.\n* Have had a prior anti-cancer biologic agent (including immune checkpoint inhibitors) or chemotherapy within 26 weeks prior to Cycle 1 Day 1 (C1D1) Subjects participating in observational studies are eligible.\n* Have previously received topoisomerase 1 inhibitors, SG or EV\n* Have an active second malignancy. Subjects with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to start of therapy on trial (Cycle 1 Day 1 \\[C1D1\\]), or subjects with surgically-cured tumors with low risk of recurrence are allowed to enroll.\n* Have known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking ≤10 mg\u002Fday of prednisone or its equivalent. All subjects with carcinomatous meningitis are excluded regardless of clinical stability.\n* Have active cardiac disease, defined as:\n\n  * Myocardial infarction or unstable angina pectoris within 6 months prior to C1D1\n  * History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation\n* New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of \\\u003C 40%\n* Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of C1D1\n* Have active serious infection requiring antibiotics (Contact sponsor PI or Co-PI for clarification)\n* Have other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.\n* Patients with conditions requiring high doses of steroids (\\>10 mg\u002Fday of prednisone or equivalent) or other immunosuppressive medications are excluded. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.\n* History idiopathic pulmonary fibrosis; organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.\n* Participants who are receiving any other investigational agents.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab, EV or SG or any excipient contained in the drug formulations (including 2 (N morpholino) ethane sulfonic acid (MES), histidine, treahalose dihydrate polysorbate 80 and polysorbate 20).\n* Participants with uncontrolled intercurrent illness.\n* Participants with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1C \\>8% or 7-8% with associated diabetes symptoms that are otherwise not explained\n* Uncontrolled tumor related bone pain or impending spinal cord compression.\n* History of autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).\n\n  1. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.\n  2. Brief (\\\u003C7 days) use of systemic corticosteroids is allowed when use is considered standard of care.\n  3. Subjects with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma\u002Fatopy will not be excluded.\n  4. Subjects requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded.\n  5. Subjects with hypothyroidism that is stable with hormone replacement or Sjögren's syndrome will not be excluded.",{"count":588,"type":20},106,[23,118],"Phase I of this research study will assess what doses of Sacituzumab Govitecan and Enfortumab Vedotin can be safely combined in the treatment of metastatic urothelial carcinoma (mUC). In Phase II of the study, patients in one of the two cohorts will receive Sacituzumab Govitecan, Enfortumab Vedotin, and Pembrolizumab to assess the efficacy of this drug combination.\n\nThe names of the study drugs in these investigational combinations are:\n\n* Enfortumab Vedotin\n* Sacituzumab Govitecan\n* Pembrolizumab",[592,26,593,241],"Urothelial Cancer","Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter",[341,26,593,241],"2025-11-03",{"date":597,"type":32},"2025-11-04",{"date":599,"type":32},"2021-05-20",{"date":601,"type":20},"2028-05-01",{"name":603,"class":227},"Dana-Farber Cancer Institute",{"id":605,"slug":606,"hasResults":11,"nctId":607,"briefTitle":608,"officialTitle":609,"acronym":4,"eligibilityCriteria":610,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":611,"targetDuration":4,"studyType":21,"phases":613,"briefSummary":614,"conditions":615,"keywords":629,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":633,"lastUpdatePostDateStruct":634,"startDateStruct":636,"completionDateStruct":638,"leadSponsor":640,"locationsCount":642},"100447533","phase-1-a-study-of-nx-1607-in-adults-with-advanced-malignancies-100447533","NCT05107674","A Study of NX-1607 in Adults With Advanced Malignancies","A Phase 1a, Dose Escalation, Safety and Tolerability Study of NX-1607, a Casitas B-lineage Lymphoma Proto-oncogene (CBL-B) Inhibitor, in Adults With Advanced Malignancies, With Phase 1b Expansion in Select Tumor Types","Key Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Measurable disease per disease-specific response criteria.\n* Patients must have disease that is metastatic or unresectable and have received standard treatment options, are not candidates for standard treatment options, or will otherwise be prevented from receiving any standard treatment options.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Minimum of 3 weeks or 5 half-lives (whichever is shorter) since last dose of systemic cancer therapy (unless otherwise specified) or minimum of 2 weeks since last radiotherapy, or minimum of 6 weeks since last systemic therapy with nitrosoureas, antibody-drug conjugate, or radio immuno-conjugate therapy.\n* Adequate organ and bone marrow function, in the absence of growth factors (with limited exception for DLBCL), as defined by laboratory parameters.\n* Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol.\n* Patient must be willing and able to adhere to the prohibitions and restrictions specified in the protocol.\n* Each patient must sign an informed consent form (ICF).\n* Histological or cytological diagnosis of platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma; gastric\u002FGEJ cancer; HNSCC; recurrent and either metastatic or unresectable melanoma; NSCLC; mCRPC; MPM; TNBC; locally advanced or metastatic urothelial cancer; cervical cancer; MSS CRC; or DLBCL (including DLBCL-RT)\n* Accessible tumor (for all cohorts) or lymph node (DLBCL only) for biopsy (Phase 1b only).\n\nKey Exclusion Criteria:\n\n* Active untreated brain metastases.\n* Patient has any of the following:\n* Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or ongoing active infection requiring systemic therapy.\n* Patients with primary refractory EOC defined as patients who do not respond to their first platinum-containing regimen or who relapse less than 6 months after completion of that first platinum-containing regimen\n* Psychiatric illness that would limit compliance with study requirements.\n* Treatment with any of the following prior to the first dose of NX-1607: CPI (anti-PD-1, PD-L1, cytotoxic T-lymphocyte-associated protein 4, etc) within 3 weeks; autologous or allogeneic stem cell transplant within 100 days; prior systemic cancer therapy within 3 weeks or 5 half-lives (whichever is shorter) (unless otherwise specified) (including hormonal therapy except for hormonal prophylaxis for a prior malignancy); prior radiotherapy within 2 weeks; prior systemic therapy with nitrosoureas, antibody-drug conjugate, or radio-immuno-conjugate therapy within 6 weeks; use of strong or moderate CYP3A4 inducers or inhibitors within 14 days or 7 days, respectively, or 5 half-lives (whichever is longer)\n* History of CAR-T therapy within 30 days prior to the first dose of NX-1607.\n* Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less except for Grade 2 alopecia and Grade 2 peripheral neuropathy or patients receiving endocrine replacement therapy\n* Patients who experienced Grade 3 or higher irAEs with prior immunotherapy.\n* History of uveitis, or 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) is not considered a form of systemic treatment and is allowed.\n* Unable to swallow capsules or has malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction likely to interfere with the delivery, absorption, or metabolism of NX-1607.\n* Known allergies, hypersensitivity, or intolerance to components of NX-1607.\n* Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of NX-1607.\n* Patient is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of NX-1607 and, as applicable, within 6 months after the last dose of paclitaxel.\n* Patient has had major surgery (e.g., requiring general anesthesia) within 4 weeks before the planned first dose of NX-1607, or will not have fully recovered from surgery, or has surgery planned during the time the patient is expected to participate in the study or within 4 weeks after the last dose of NX-1607. Note: Patients with minor planned surgical procedures to be conducted under local anesthesia may participate.\n* Vaccinated with a live vaccine within 28 days (with the exception of the annual inactivated influenza vaccine) or COVID-19 vaccination within 14 days prior to the first dose of NX-1607.\n* Active known second malignancy with the exception of any of the following:\n\n  * Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer.\n  * Adequately treated Stage I cancer from which the patient is currently in remission and has been in remission for ≥ 2 years.\n  * Low-risk prostate cancer with Gleason score \\\u003C 7 and PSA \\\u003C 10 ng\u002FmL.\n  * Any other cancer from which the patient has been disease-free for ≥ 2 years.\n* Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Patients with well controlled HIV (e.g., CD4 \\> 350\u002Fmm3 and undetectable viral load) are eligible.\n* Current active hepatitis, including hepatitis A (hepatitis A virus immunoglobulin M \\[IgM\\] positive), hepatitis B (hepatitis B virus \\[HBV\\] surface antigen positive), or hepatitis C (hepatitis C virus \\[HCV\\] antibody positive, confirmed by HCV RNA). Patients with HCV with undetectable virus after treatment are eligible. Patients with prior exposure to HBV may be entered if quantitative PCR is negative.\n* Use of systemic corticosteroids (\\> 20 mg prednisone or equivalent) within 15 days (except for prophylaxis for radio diagnostic contrast reactions and\u002For prophylaxis for patients receiving paclitaxel), or other immunosuppressive drugs within 30 days, prior to the first dose of NX-1607.\n* Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 µg \\[NIH 2020\\] (Note: Patients who switch from a high dose to a dose of 30 µg\u002Fday or less at least 1 day prior to Screening assessments are eligible for study entry).\n* Receipt of an IP or has been treated with an investigational device within 3 weeks or 5 half-lives (whichever is shorter) prior to the first dose of NX-1607.\n* Any of the following within 6 months prior to the first dose of NX-1607 or ongoing:\n\n  * Myocardial infarction\n  * Unstable angina\n  * Unstable symptomatic ischemic heart disease\n  * New York Heart Association Class III or IV heart failure\n  * Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events)\n  * Any other significant cardiac condition (e.g., pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart disease)\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 participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator in consultation with the Medical Monitor.",{"count":612,"type":20},345,[23],"This is a first-in-human Phase 1a\u002F1b multicenter, open-label oncology study designed to evaluate the safety and anti-cancer activity of NX-1607 in patients with advanced malignancies.",[616,617,618,619,620,621,622,623,624,26,625,626,627,628],"Ovarian Cancer, Epithelial","Gastric Cancer","GastroEsophageal Junction (GEJ) Cancer","Head and Neck Squamous Cell Carcinoma","Metastatic or Unresectable Melanoma","Non-small Cell Lung Cancer (NSCLC)","Metastatic Castration-resistant Prostate Cancer (mCRPC)","Malignant Pleural Mesothelioma (MPM)","Triple Negative Breast Cancer (TNBC)","Cervical Cancer","Diffuse Large B Cell Lymphoma (DLBCL)","Richter Transformation","Microsatellite Stable Colorectal Carcinoma",[630,631,632],"Ubiquitin Ligase Inhibitor","Advanced Malignancies","T-cell Activation","2025-09-05",{"date":635,"type":32},"2025-09-09",{"date":637,"type":32},"2021-09-29",{"date":639,"type":20},"2028-02-28",{"name":641,"class":104},"Nurix Therapeutics, Inc.",17,{"id":644,"slug":645,"hasResults":11,"nctId":646,"briefTitle":647,"officialTitle":648,"acronym":4,"eligibilityCriteria":649,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":650,"targetDuration":4,"studyType":21,"phases":652,"briefSummary":653,"conditions":654,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":656,"lastUpdatePostDateStruct":657,"startDateStruct":659,"completionDateStruct":661,"leadSponsor":663,"locationsCount":105},"100554012","phase-2-modular-trial-of-sephb4-hsa-in-ephrinb2-high-solid-tumors-100554012","NCT06493552","Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors","A Modular, Open Label, Randomized Phase II\u002FIII Trial to Assess Efficacy of Combining sEphB4-HSA (EphrinB2 Inhibitor) With Immunotherapy Regimens in Patients With EphrinB2-High Solid Tumors","Inclusion Criteria:\n\nGeneral Inclusion Criteria for Both Arms\n\n* Willing and able to provide informed consent.\n* Men and women 18 years of age, or older.\n* Must provide the cell block or a minimum of 15 slides from the diagnostic biopsy or archival tissue.\n* Tumor tissue must be submitted for molecular profile through a commercial service such as Tempus, CARIS, Foundation One, etc. This must include a PD-L1 assay.\n* Tumor must express EphrinB2 as assessed by USC Norris Core Lab.\n* Zubrod performance status of less than or equal to 1.\n* Women of childbearing potential must use method(s) of contraception. The individual methods of contraception should be determined in consultation with the treating physician or investigator.\n* Women of childbearing potential are eligible if serum pregnancy test obtained during screening is negative. Women are also eligible if one of the following criteria is met:\n\n  * Have undergone a documented hysterectomy and\u002For bilateral oophorectomy; OR\n  * Have medically confirmed ovarian failure; OR\n  * Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; OR\n  * A serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal women.\n* Women must not be breastfeeding.\n* Men who are sexually active with women of childbearing potential must agree to use 2 contraceptive methods with a failure rate of less than 1% per year.\n\n  o NOTE: Contraception should be continued using two highly effective methods for a period of 120 days after the last dose of treatment.\n* Adequate organ function as defined below using baseline laboratory requirements obtained within 14 days prior to randomization:\n\n  * Measured or calculated creatinine clearance (CrCl) greater than or equal to 30 mL\u002Fmin using the Cockcroft-Gault formula using actual weight (NOT ideal or adjusted weights).\n  * WBC ≥2000\u002FuL\n  * Neutrophils ≥1500\u002FuL\n  * Platelets ≥100x103\u002FuL\n  * Hemoglobin ≥9g\u002FdL\n  * AST ≤3 x ULN\n  * ALT ≤3 x ULN\n  * Bilirubin ≤1.5 x ULN\n\nModule A Inclusion Criteria\n\n* Urothelial carcinoma, variant components and differentiations allowed. Pure small cell not allowed.\n* cT2 to cT4a N0M0, by TURBT or imaging.\n* No systemic therapy for cancer in the previous 12 months.\n* Choice of treatment if randomized to the control arm must be declared prior to randomization. If cisplatin ineligible or refusing, pembrolizumab must be approved by patient's insurance prior to randomization.\n\nModule B inclusion Criteria\n\n* Urothelial carcinoma, variant components and differentiations allowed. Pure small cell not allowed.\n* Tumor must be Nectin4 non-amplified- testing performed during pre-screening assessment.\n* No systemic therapy for cancer in the previous 12 months.\n* Measurable disease as defined by RECIST1.1 criteria\n\nExclusion Criteria:\n\n* Patients with known symptomatic brain metastases requiring systemic corticosteroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. Mild neurological deficit is allowed, if it does not interfere with the ability to judge the safety on the trial.\n* History of or active autoimmune disorders (including but not limited to: Crohn's Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that compromise or impair the immune system.\n* Known active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) -related illness. Routine testing is not required; however, treating physicians may use their discretion to determine whether testing is necessary.\n* Uncontrolled adrenal insufficiency.\n* Any known active chronic liver disease.\n* Concurrent or active second malignancy requiring systemic therapy is excluded.\n* Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.\n* Major surgery less than 6 weeks prior to the first dose of study drug. Minor surgery less than 4 weeks prior to the first dose of study drug. Insertion of vascular access device ≥ 7 days prior to 1st dose of study drug is allowed.\n* History of severe hypersensitivity reaction to any monoclonal antibody.",{"count":651,"type":20},700,[118,51],"Patients with solid tumors that have high expression levels of EphrinB2 are treated with regimens that include EphrinB2 inhibitor, sEphB4-HSA. The primary objective of this study is to demonstrate additive therapeutic benefit for sEphB4-HSA. The secondary objectives are to determine whether the sEphB4-HSA containing regimen is safe and whether the oncological endpoints of importance in each cohort improve as a result of treatment with sEphB4-HSA containing regimen relative to a predefined threshold or to a control arm in the cohort where available. Treatment continues until progression of disease or unacceptable toxicities arise.",[655,26],"Muscle-Invasive Bladder Carcinoma","2025-03-30",{"date":658,"type":32},"2025-04-03",{"date":660,"type":32},"2025-03-15",{"date":662,"type":20},"2034-08",{"name":664,"class":104},"Vasgene Therapeutics, Inc",{"id":666,"slug":667,"hasResults":11,"nctId":668,"briefTitle":669,"officialTitle":670,"acronym":4,"eligibilityCriteria":671,"healthyVolunteers":11,"sex":672,"minAge":673,"maxAge":4,"enrollmentInfo":674,"targetDuration":4,"studyType":360,"phases":4,"briefSummary":675,"conditions":676,"keywords":677,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":684,"lastUpdatePostDateStruct":685,"startDateStruct":687,"completionDateStruct":689,"leadSponsor":691,"locationsCount":105},"100411775","urine-omics-predicting-io-therapy-responses-in-muc-patients-100411775","NCT04641936","Urine Omics Predicting IO Therapy Responses in mUC Patients","Urine Metabolomics and Proteomics Profiling to Predict the Responses and Adverse Events of Immuno-Oncology-based Therapy in Patients With Metastatic Urothelial Carcinoma","Inclusion Criteria:\n\n* 1\\. Age \\> 20 years\n* 2\\. Subjects diagnosed as metastatic urothelial carcinoma (mUC)\n* 3\\. Subjects who are about to receive IO-based therapy\n* 4\\. ECOG performance 0, 1, 2, and 3\n* 5\\. Life expectancy 3 months\n* 6\\. eGFR \\> 15 ml\u002Fmin\u002F1.73 m2 (Stage IV Chronic Kidney Disease or better)\n* 7\\. Willing to sign the informed consent form\n\nExclusion Criteria:\n\n* 1\\. Subjects NOT willing to sign the informed consent form\n* 2\\. Subjects with active infection or active urinary tract infection, as shown by urinary WBC \\> 5\u002FHPF\n* 3\\. Subjects having co-existing other malignancies that need active treatment. Those with other malignancies that do not need active treatment are allowed to join the study.\n* 4\\. Subjects taking any immune-modulating agents, including but not limited to corticosteroid, immune-suppressants, etc. at the discretion of recruiting investigators\n* 5\\. Subjects who have taken any CPIs before. However, subjects who have received intravesical or intrapelvic BCG instillation are allowed to enroll.\n* 6\\. Subjects who have received anti-FGFR therapy, enfortumab vedotin or other systemic therapies within 12 weeks of screening are not allowed. However, subjects who had a washout period of the above agents for \\>12 weeks are allowed to enroll. Subjects who have received or are receiving cytotoxic chemotherapy are allowed to join the study.","MALE","20 Years",{"count":537,"type":20},"The study aims to identify urinary metabolite and protein markers that can predict anti-tumor efficacy and adverse events in subjects receiving IO-based therapies for metastatic urothelial carcinoma.",[26],[365,678,679,680,681,682,683],"biomarkers","clinical responses","IO-based therapies","metabolomics","proteomics","Urine","2024-04-15",{"date":686,"type":32},"2024-04-17",{"date":688,"type":32},"2020-12-17",{"date":690,"type":20},"2027-10-31",{"name":692,"class":227},"National Taiwan University Hospital",{"id":694,"slug":695,"hasResults":11,"nctId":696,"briefTitle":697,"officialTitle":698,"acronym":4,"eligibilityCriteria":699,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":700,"targetDuration":4,"studyType":21,"phases":702,"briefSummary":703,"conditions":704,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":728,"lastUpdatePostDateStruct":729,"startDateStruct":731,"completionDateStruct":732,"leadSponsor":734,"locationsCount":105},"100495576","phase-2-cpi-613-devimistat-in-combination-with-hydroxychloroquine-and-5-fluorouracil-or-gemcitabine-in-treating-patients-with-advanced-chemorefractory-solid-tumors-100495576","NCT05733000","CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors","Phase II Open-Label Multi-Cohort Study Evaluating CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Patients With Advanced Chemorefractory Colorectal, Pancreatic, or Other Solid Cancers","Inclusion Criteria:\n\n* Patients must have histologically confirmed cancer for which standard-of-care curative measures are no longer effective or be intolerant to those agents. Patients in cohort 1 must have colorectal cancer. Patients in cohort 2 must have pancreatic cancer. Patients in cohort 3 may have any of the following cancers:\n\n  * Biliary\n  * Gastroesophageal\n  * Urothelial\n  * Ovarian\n  * Non-small cell lung (adenocarcinoma only)\n* Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 disease.\n* Patients must have radiographic documentation of metastatic disease with imaging within =\\\u003C 6 weeks prior to registration.\n* Patients must be age \\>= 18 years.\n* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Performance Status of 2 will be allowed with approval from principle investigator (PI) on a case-by case basis.\n\n  * Note: Performance status of 2 will be allowed with approval from PI on a case-by case basis. Documentation of PI approval in these cases will be stored with inclusion\u002Fexclusion signed checklist for patient and\u002For in patient's shadow chart.\n* Patients must have exhausted all available molecularly targeted therapies (e.g., anti-PD-1\u002Fanti-PD-L1 agents where indicated).\n* Absolute neutrophil count (ANC) \\>= 1,500\u002FmcL (within the last 14 days of screening)\n* Hemoglobin (Hgb) \\>= 9 g\u002FdL (within the last 14 days of screening) (Transfusions permitted. Eligibility labs should be drawn \\>= 7 days from transfusion).\n* Platelets (PLT) \\>= 100,000\u002FmcL (within the last 14 days of screening) (Transfusions permitted. Eligibility labs should be drawn \\>= 7 days from transfusion).\n* INR (international normalized ratio) =\\\u003C 1.6 (within the last 14 days of screening) (unless receiving anticoagulation therapy) If receiving anticoagulant: INR =\\\u003C 3.0 and no active bleeding, (i.e., no bleeding within 14 days prior to first dose of study therapy).\n* Total bilirubin =\\\u003C1.5 x Institutional upper limit of normal (ULN) (within the last 14 days of screening)\n\n  * Note: Patients with Gilbert's Syndrome are exempt. Patients with liver metastases with no significant bilirubin obstruction may have a total bilirubin level of =\\\u003C 2.0 mg\u002FdL.\n* Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) =\\\u003C 2.5 x institutional ULN (within the last 14 days of screening)\n\n  * Note: If liver metastases are present, then =\\\u003C 5 x ULN is allowed.\n* Alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) =\\\u003C 2.5 x institutional ULN (within the last 14 days of screening)\n\n  * Note: If liver metastases are present, then =\\\u003C 5 x ULN is allowed.\n* Serum albumin \\> 3.0 g\u002FdL (within the last 14 days of screening)\n* Creatinine =\\\u003C 1.5 x ULN OR glomerular filtration rate (GFR) \\>= 50 mL\u002Fmin\u002F1.73 m\\^2 (within the last 14 days of screening)\n\n  * eGFR is estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation\n* The effects of combination treatment of CPI-613, 5-FU, gemcitabine, and HCQ on the developing human fetus are unknown. For this reason and because antineoplastic agents as well as other therapeutic agents used in this trial are known to be teratogenic, patients of child-bearing potential (POCBP) regardless of gender must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 180 days following completion of therapy. Patients who can impregnate their partners regardless of gender must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 180 days following completion of therapy. Should a patient become pregnant or suspect they are pregnant while they or their partner is participating in this study, they should inform their treating physician immediately.\n\n  * Note: At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence \\[e.g., calendar, ovulation, symptothermal, postovulation methods\\] and withdrawal are not acceptable methods of contraception.)\n  * Note: A POCBP is any person with an egg-producing reproductive tract (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:\n\n    * Has not undergone a hysterectomy or bilateral oophorectomy\n    * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \\> 12 months)\n* POCBP must have a negative pregnancy test prior to registration on study.\n\n  * Note: If negative pregnancy test result is \\>7 days from first dose of study treatment it must be repeated at time of first dose of study treatment (with any of the four drugs used in this study).\n* For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration.\n* For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment, must have an undetectable HCV viral load. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardio toxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. Patients must be class 2B or better.\n\n  * Note: Patients with pacemakers where corrected QT interval (QTc) is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study.\n* Patients must have the ability to understand and the willingness to sign a written informed consent document for the duration of the entirety of the study.\n* Patients must be reliable, willing to make themselves available for the duration of the entire study and willing to follow screening procedures.\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1).\n\n  * Note: Patients who experience adverse events of alopecia and peripheral neuropathy that have not recovered are eligible; patients with any lab abnormality that is above grade 1 related to previous therapy found to be not clinically significant will also be eligible.\n* Patients with symptomatic brain metastases currently using corticosteroids.\n\n  * Note: Patients with brain metastases who are asymptomatic and off corticosteroids for at least one week are eligible.\n* Patients with severe obstructive pulmonary disease or interstitial lung disease.\n* Patients with a history of myocardial infarction that is \\\u003C90 days prior to registration.\n* Patients using concomitant medications that prolong the QT\u002FQTc intervals. For example, patients receiving amiodarone. Using amiodarone together with hydroxychloroquine can increase the risk of long QT syndrome that although rare, may be serious, and potentially life-threatening.\n* Patients with a history of additional risk factors for drug-induced QT prolongation or Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome).\n* Patients with major surgery or significant traumatic injury =\\\u003C 21 days prior to registration.\n* Patients receiving treatment with low dose chemotherapy concurrent with radiation =\\\u003C 21 days prior to registration.\n\nOR patients who have had chemotherapy or radiotherapy =\\\u003C 21 days (42 days for nitrosoureas or mitomycin C) prior to registration.\n\n* Note: Palliative radiation before and during study participation is permissible providing it is not to a target lesion.\n\n  * Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:\n* Ongoing or active infection requiring systemic treatment.\n* Clinically significant complications such as perforation, gastrointestinal bleeding, or diverticulitis within 42 days prior to registration.\n* Symptomatic congestive heart failure; symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarction.\n* Unstable angina pectoris.\n* Unstable cardiac arrhythmia.\n* Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Active substance abuse.\n* Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints.\n\n  * Patients who are pregnant or nursing.\n  * Patients with Fridericia-corrected QT interval (QTcF) \\> 470 msec (female) or \\> 450 (male), or history of congenital long QT syndrome. Any electrocardiogram (ECG) abnormality that in the opinion of the investigator would preclude safe participation in the study.\n  * Patients who have pre-existing retinopathy of the eye.\n  * Patients who are unable to swallow or retain and absorb oral medication\n  * Patients with known hypersensitivity to any of the following: CPI or its inactive components, 4-aminoquinoline compounds, or quinine.\n  * Patients with poorly controlled diabetes mellitus (glycosylated hemoglobin (HbA1c) of \\> 7%, pre-prandial capillary plasma glucose \\> 130mg\u002Fdl, and peak postprandial capillary plasma glucose of \\> 180mg\u002Fdl).",{"count":701,"type":20},94,[118],"This phase II trial tests how well CPI-613 (devimistat) in combination with hydroxychloroquine (HCQ) and 5-fluorouracil (5-FU) or gemcitabine works in patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that have not responded to chemotherapy medications (chemorefractory). Metabolism is how the cells in the body use molecules (carbohydrates, fats, and proteins) from food to get the energy they need to grow, reproduce and stay healthy. Tumor cells, however, do this process differently as they use more molecules (glucose, a type of carbohydrate) to make the energy they need to grow and spread. CPI-613 works by blocking the creation of the energy that tumor cells need to survive, grow in the body and make more tumor cells. When the energy production they need is blocked, the tumor cells can no longer survive. Hydroxychloroquine is a drug used to treat malaria and rheumatoid arthritis and may also improve the immune system in a way that tumors may be better controlled. Fluorouracil is in a class of medications called antimetabolites. It works by killing fast-growing abnormal cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. CPI-613 (devimistat) in combination with hydroxychloroquine and 5-fluorouracil or gemcitabine may work to better treat advanced solid tumors.",[705,706,707,708,709,710,711,517,128,132,712,308,159,713,714,715,26,716,717,718,719,720,721,722,723,399,172,724,725,314,189,726,727],"Advanced Biliary Tract Carcinoma","Advanced Colorectal Carcinoma","Advanced Gastroesophageal Junction Adenocarcinoma","Advanced Lung Adenocarcinoma","Advanced Malignant Solid Neoplasm","Advanced Ovarian Carcinoma","Advanced Pancreatic Carcinoma","Metastatic Biliary Tract Carcinoma","Metastatic Lung Adenocarcinoma","Metastatic Ovarian Carcinoma","Metastatic Pancreatic Carcinoma","Refractory Biliary Tract Carcinoma","Refractory Colorectal Carcinoma","Refractory Gastroesophageal Junction Adenocarcinoma","Refractory Lung Adenocarcinoma","Refractory Ovarian Carcinoma","Refractory Pancreatic Carcinoma","Refractory Urothelial Carcinoma","Stage II Pancreatic Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","2023-03-08",{"date":730,"type":32},"2023-03-10",{"date":728,"type":32},{"date":733,"type":20},"2030-03-04",{"name":735,"class":227},"Northwestern University"]