[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Vall d'Hebron Institute of Oncology\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":280},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,10,0,[8,45,70,94,116,145,167,193,218,245],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":29,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100568401","phase-2-single-cell-profiling-persistance-to-immunotherapy-100568401",false,"NCT06680739","Single cEll pRofiling PErsistaNce To ImmuNothErapy","Single Cell Characterization of Persistent Cells Upon Treatment With Durvalumab (MEDI4736) With or Without Tremelimumab in MSS and MSI Colorectal and Endometrial Tumors: the SERPENTINE Clinical Trial","SERPENTINE","Inclusion Criteria:\n\n* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union \\[EU\\] Data Privacy Directive in the EU) obtained from the patient\u002Flegal representative prior to performing any protocol-related procedures, including screening evaluations.\n* Age \\> 18 years at time of study entry.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n\n  1. Cohort 1: histologically confirmed recurrent or metastatic CRC or endometrial cancer irrespective of prior treatment history with chemotherapy and\u002For targeted agents, not amenable to surgery and known tumor MSI-H or dMMR status per local standard of practice.\n  2. Cohort 2: histologically confirmed recurrent or metastatic CRC not amenable to surgery and known tumor MSS or pMMR status per local standard of practice, that have progressed during or after, at least 2 lines of fluoropyrimidine, irinotecan and\u002For oxaliplatin containing therapy with or without bevacizumab according to institutional practice or have not tolerated therapy for advanced\u002Fmetastatic disease; if epidermal growth factor receptor (EGFR) positive\u002FRAS wild type, prior anti-EGFR treatment is required. Or histologically confirmed recurrent or metastatic endometrial cancer that have progressed during or after a platinum and taxane-based regimen, not amenable to surgery and known tumor MSS or pMMR status per local standard of practice.\n* Life expectancy of \\> 12 weeks.\n* Body weight \\>30 kg.\n* Adequate normal organ and marrow function as defined below:\n\n  1. Hemoglobin ≥9.0 g\u002FdL\n  2. Absolute neutrophil count (ANC) 1.5 (or 1.0) x 109\u002FL (\\> 1500 per mm3)\n  3. Platelet count ≥100 x 109\u002FL (\\>75,000 per mm3)\n  4. Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\n  5. AST (SGOT)\u002FALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5 x ULN\n  6. Measured creatinine clearance (CL) \\>40 mL\u002Fmin or Calculated creatinine CL\\>40 mL\u002Fmin by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.\n  7. Creatinine ≤1.5 x ULN OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCla) ≥60 mL\u002Fmin for subject with creatinine levels \\>1.5 x institutional ULN. Creatinine clearance (CrCl) should be calculated per institutional standard.\n* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:\n\n  1. Women \\\u003C50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).\n  2. Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \\>1 year ago, had chemotherapy-induced menopause with last menses \\>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).\n* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n* Have at least 1 tumoral lesion of minimum 10 mm in diameter that is suitable for initial biopsy.\n* Presence of at least 1 measurable lesion according to RECIST v1.1 apart from the lesion that is biopsiable before initiating treatment.\n* Male and Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 7.1 for the course of the trial and for 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.\n\nExclusion Criteria:\n\n* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.\n* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. The following are exceptions to this criterion:\n\n  1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)\n  2. Systemic corticosteroids at physiologic doses not to exceed \\\u003C\\\u003C10 mg\u002Fday\\>\\> of prednisone or its equivalent\n  3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).\n* Has had a prior anti-cancer mAb within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to mAbs administered more than 4 weeks earlier.\n* Has had prior chemotherapy, targeted small molecule therapy, hormonal therapy or radiation therapy for cancer therapy within 2 weeks prior to study Day 1. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.\n* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:\n\n  1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.\n  2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.\n* Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study drug and patients must have recovered adequately from the eventual toxicity and\u002For complications related with the surgical procedure. Note: Local surgery of isolated lesions for palliative intent is acceptable.\n* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.\n* History of allogenic organ transplantation.\n* Has known active CNS metastases and\u002For carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of 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. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.\n* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \\[e.g., colitis or Crohn's disease\\], diverticulitis \\[with the exception of diverticulosis\\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\\]). The following are exceptions to this criterion:\n\n  1. Patients with vitiligo or alopecia\n  2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement\n  3. Any chronic skin condition that does not require systemic therapy\n  4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician\n  5. Patients with celiac disease controlled by diet alone.\n* Has evidence of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.\n* Has an active infection requiring systemic therapy, also including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \\[anti-HBc\\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.\n* Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1\u002F2 antibodies).\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. The conditions also include uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.\n* Has previously received prior therapy with an anti-PD-1, anti-PD-L1 including durvalumab, or anti CTLA-4 (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).\n* Has received a live vaccine within 30 days of planned start of study therapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.\n* Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements.","ALL","18 Years",{"count":20,"type":21},60,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","The SERPENTINE trial (ESR 21-21165) is a phase II clinical study aiming to evaluate the efficacy of durvalumab and tremelimumab, alone or in combination, in patients with colorectal or endometrial cancer. The trial targets patients with microsatellite instability-high (MSI-H) tumors and those with microsatellite stable (MSS) tumors.\n\nColorectal and endometrial cancers present significant challenges due to their heterogeneity and variable responses to treatment. Immunotherapy, particularly checkpoint inhibitors like durvalumab and tremelimumab, has shown promise in some patients, but predicting response remains elusive. The SERPENTINE trial aims to address this gap by investigating the effectiveness of these immunotherapies in a carefully selected patient population.",[27,28],"Colorectal Cancer","Endometrial Cancer",[30,31],"MSI cancer","MSS cancer","RECRUITING","2026-05-29",{"date":35,"type":36},"2026-06-01","ACTUAL",{"date":38,"type":36},"2022-03-01",{"date":40,"type":21},"2032-07-01",{"name":42,"class":43},"Vall d'Hebron Institute of Oncology","OTHER",1,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":49,"acronym":50,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":52,"targetDuration":4,"studyType":22,"phases":54,"briefSummary":56,"conditions":57,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":64,"completionDateStruct":66,"leadSponsor":68,"locationsCount":69},"100637801","phase-1-a-phase-i-interventional-open-label-non-randomized-dose-escalation-trial-to-evaluate-the-safety-tolerability-pharmacokinetics-pharmacodynamics-immunogenicity-and-preliminary-anti-tumor-activity-of-autologous-p95her2car-tech2me-t-cells-in-patients-with-selected-advanced-cancers-100637801","NCT07593820","A Phase I Interventional Open-label, Non-randomized Dose-escalation Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Preliminary Anti-tumor Activity of Autologous p95HER2.CAR-TECH2Me T Cells in Patients With Selected Advanced Cancers.","Catherine","Inclusion Criteria:\n\n1. Patients must understand and voluntarily sign an informed consent document before any study-related assessments\u002Fprocedures being conducted.\n2. Age ≥ 18 and years at the time of signing the ICF\n3. Patients must be able and willing to comply with the study visit schedule and protocol requirements.\n4. Patients must have a clinical performance of Eastern Cooperative Oncology Group 0 or 1.\n5. Life expectancy ≥12 weeks.\n6. Patients must have histologically or cytologically proven unresectable or metastatic tumors. The disease must be refractory to standard therapy or in the first line if they are unable to receive standard therapy or no standard therapy exists for a particular disease.\n\n   a) Select tumor types: breast, gastric, and endometrial tumors. Other selected solid tumors may be included per investigator discretion if the potential benefit is considered based on the literature updates in HER2\u002Fp95HER2 expression.\n7. Positivity for HER2 expression according to international society guidelines (score in a ISO-certified clinical or equivalent laboratory). To meet study entry eligibility, tumors are required to have at least an intensity score 3+ for HER2 staining following the manufacturer's recommendations\n8. Measurable disease by the RECIST v. 1.1 criteria (See Section 7.2 for details). Note: Lesions previously irradiated should not be selected as target lesions unless there has been demonstrated progression in those lesions;\n9. Patients are considered medically fit enough to undergo all study procedures and interventions and adequate hematological, renal, and hepatic functions defined by:\n\n   1. Hemoglobin ≥ 9.0 g\u002FdL.\n   2. An absolute neutrophil count ≥ 1x10E9\u002FL without the support of filgrastim\n   3. Platelets ≥ 100 x10E9\u002FL.\n   4. PT and APTT ≤ 1.5x ULN (unless receiving therapeutic anticoagulation). Note: Subjects receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose.\n   5. AST or ALT ≤ 3 x ULN. Patients with liver metastases must have AST and ALT ≤ 5.0 x ULN.\n   6. Total bilirubin \\\u003C 2 mg\u002FdL. Patients with Gilbert's Syndrome must have a total bilirubin ≤ 3.0 mg\u002FdL.\n   7. Serum creatinine \\\u003C 1.5 mg\u002FdL or measured creatinine clearance ≥ 50 ml\u002Fmin calculated using the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female)\u002F72 × (serum creatinine in mg\u002FdL).\n10. Patients must be seronegative for HIV antibody.\n11. Patients must be seronegative for active hepatitis B (defined as having a negative hepatitis B surface antigen \\[HBsAg\\] test), and seronegative for hepatitis C antibody. Patients with a history of hepatitis B virus (HBV) infection and having a negative HBsAg test and a positive antibody to hepatitis B surface antigen (HBsAg) are eligible. Patients with the hepatitis C antibody test positive are eligible only if tested for the presence of antigen by RT-PCR and be HCV RNA negative.\n12. Patients must have blood tests results negative for active tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, HTLV or Epstein-Barr virus infection.\n13. Patients with documented LVEF of ≥ 50%.\n14. Patients with documented FEV1, FVC, and DLCO ≥ 50% tested by a pulmonary function test.\n15. Patients who are of childbearing potential (postmenarcheal who has not reached a postmenopausal state and has not undergone surgical sterilization) or have partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 12 months after the infusion of the p95HER2.CAR-TECH2Me product .\n16. Female participants: a female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:\n\n    1. Women of non-childbearing potential (WONCBP).\n    2. Women of childbearing potential (WOCBP), who:\n\n    i) Agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year from screening until 12 months after the infusion of the p95HER2.CAR-TECH2Me product. Examples of contraceptive methods with a failure rate of \\\u003C1% per year include bilateral tubal occlusion, male sterilization, and copper intrauterine devices.\n\n    ii) Have a negative pregnancy test (blood) within one week before the first study treatment administration (applicable to premenopausal women and women 2 years after the start of menopause (menopause is defined as amenorrhea for \\\u003C 2 years).\n17. Male Participants: during the treatment period and for at least 6 months after the last dose of study treatment, agreement to:\n\n    1. Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom or a contraceptive method that result in a failure rate of \\\u003C1% per year, with partners who are WOCBP.\n    2. Refrain from donating sperm during the study.\n    3. Inform if his partner gets pregnant during this time.\n18. Adequate expanding p95HER2.CAR-TECH2Me cells as defined by the T cell production manual before preparative lymphodepleting chemotherapy infusion (available autologous transduced T lymphocytes with 15% or more expression of p95HER2.CAR-TECH2Me as determined by flow-cytometry and killing of p95HER2-positive targets 20 % or greater in cytotoxicity assay.)\n19. Any toxicity related to prior systemic therapy must have recovered to grade 1 or less according to NCI-CTCAE v5.0 at least 4 weeks before treatment enrollment, except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy.\n\n    Note: Other Grade 2 AEs that are deemed clinically insignificant by treating physician and in consultation with Medical Monitor are permitted.\n20. Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.\n\nExclusion Criteria:\n\n1. Patients with symptomatic and\u002For untreated brain metastases. Note: Patients with definitively-treated brain metastases will be considered for enrollment after discussion with Medical Monitor if prior to the start of NMA-LD the patient is asymptomatic, clinically stable for ≥3 months, there are no new brain lesions via magnetic resonance imaging (MRI) post-treatment, and the patient does not require corticosteroid treatment.\n2. Patients with leptomeningeal carcinomatosis.\n3. Patients with an active concurrent or history within the past 3 years of invasive malignancy, except for non-melanoma skin cancer, cervical and bladder carcinoma in situ, good prognosis ductal carcinoma in situ of the breast, or prostate carcinoma that is in remission under androgen deprivation therapy for \\> 2 years. Other exceptions may apply and require discussion between the Investigator and the Medical Monitor.\n4. Patients with an active systemic infection requiring anti-infective treatment within 14 days before preparative lymphodepleting therapy.\n5. Patients with active hepatitis B or hepatitis C.\n6. Patients with active autoimmune disease requiring immunosuppressive treatments.\n7. Patients with a history of organ or bone marrow transplantation.\n8. Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).\n9. Patients requiring regular treatment with steroids. Note: use of inhaled, topical steroids and use of systemic physiologic corticosteroid replacement therapy are permitted.\n10. Patients with current or history within the last 6 months, as determined by the Investigator, of clinically significant, progressive, and\u002For uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.\n11. Patients with a history of coronary revascularization or ischemic symptoms.\n12. History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin)\n13. Patients with allergies to any of the compounds included in any of the treatment products.\n14. Patients with contraindications for cyclophosphamide and fludarabine at per protocol doses (see Investigator Brochure for details).\n15. Patients who have received any approved anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy within 4 weeks before preparative lymphodepleting therapy.\n\n    Exception: palliative radiotherapy for bone metastasis \\> 2 weeks before preparative lymphodepleting therapy, denosumab, bisphosphonates, androgen deprivation therapy for prostate cancer and hormonal therapy for breast cancer.\n16. Patients who have received any non-cytotoxic drug and molecular targeted therapy within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).\n17. Patients who have received any investigational agent within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).\n18. Patients who have received a live, attenuated vaccination within the 4 weeks before lymphodepleting therapy.\n19. Patients who have undergone major surgery in the previous 3 weeks before lymphodepleting therapy.\n20. Patients who have previously received any investigational cell or gene therapies.\n21. Women of childbearing potential who are pregnant or breastfeeding.\n22. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.\n23. Other severe, acute, or chronic medical condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator.",{"count":53,"type":21},15,[55],"PHASE1","This is a phase I, open-label, non-randomized, multicenter, dose-escalation trial designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of autologous p95HER2.CAR-TECH2Me T cells in patients with selected advanced HER2-positive (3+) cancers, including locally advanced, recurrent, or metastatic breast, gastric, endometrial, and other selected solid tumors. The study will also assess pharmacokinetics, pharmacodynamics, and immunogenicity of p95HER2.CAR-TECH2Me following intravenous administration.\n\nTreatment consists of non-myeloablative lymphodepletion chemotherapy with cyclophosphamide and fludarabine administered on Days -4 to -2, followed by a single infusion of p95HER2.CAR-TECH2Me cells on Day 0. The investigational product is a live cell suspension of autologous CAR-T lymphocytes derived from the patient's peripheral blood. Premedication will be administered before cell infusion according to protocol requirements.\n\nThe primary objective of the study is to evaluate the safety and tolerability of p95HER2.CAR-TECH2Me and to identify the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Primary endpoints include the nature and frequency of adverse events, serious adverse events, clinically relevant changes in laboratory parameters, electrocardiograms, vital signs, physical examination findings, and ECOG performance status, as well as the incidence and nature of dose-limiting toxicities. Adverse events will be graded according to NCI CTCAE v5.0, with cytokine release syndrome and neurotoxicity graded according to established consensus criteria.\n\nSecondary objectives include evaluation of preliminary anti-tumor activity and survival outcomes. Secondary endpoints include objective response rate, duration of response, progression-free survival according to RECIST v1.1 as assessed by the investigator, and overall survival.\n\nApproximately 15 patients are planned for enrollment over an estimated 36 to 48 months. The total study duration is expected to be approximately 60 months from the time the first subject signs the pre-screening informed consent form until the last subject completes the final study-related follow-up contact.",[58,59,60],"Metastatic Gastric Cancer","Metastatic Breast Cancer","Endometrial Cancer Metastatic","2026-05-19",{"date":63,"type":36},"2026-05-22",{"date":65,"type":36},"2026-04-29",{"date":67,"type":21},"2041-04-01",{"name":42,"class":43},2,{"id":71,"slug":72,"hasResults":11,"nctId":73,"briefTitle":74,"officialTitle":75,"acronym":76,"eligibilityCriteria":77,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":78,"targetDuration":4,"studyType":22,"phases":80,"briefSummary":81,"conditions":82,"keywords":4,"overallStatus":84,"whyStopped":4,"lastUpdateSubmitDate":85,"lastUpdatePostDateStruct":86,"startDateStruct":88,"completionDateStruct":90,"leadSponsor":92,"locationsCount":93},"100638689","phase-2-pembrolizumab-plus-belzutifan-with-or-without-lenvatinib-in-localized-renal-cell-carcinoma-100638689","NCT07593040","Pembrolizumab Plus Belzutifan With or Without Lenvatinib in Localized Renal Cell Carcinoma","A Randomized Phase 2 Trial of Neoadjuvant Pembrolizumab Plus Belzutifan With or Without Lenvatinib in Patients With Localized Renal Cell Carcinoma","Moonlanding","Inclusion Criteria:\n\n* Male\u002Ffemale participants who are at least 18 years of age on the day of signing informed consent.\n\n  2\\. Willing to provide written informed consent. They may also provide consent for Future Biomedical Research; however, the participant may participate in the main trial without participating in the Future Biomedical Research.\n\n  3\\. Histologically confirmed diagnosis of RCC with a clear cell component with or without sarcomatoid features. Diagnosis is to be made by the investigator and does not require central histology review.\n\n  4\\. Tumours must be T2 with grade 4, T3, T4, or any T with N1, M0 on radiographic imaging using TNM staging (8th edition)\n  1. T2 is defined as a tumour \\>7cm but limited to the kidney; grade 4 is per the International Society of Urological Pathology (ISUP) grading.\n  2. T3 is defined as tumour extension into major veins or perinephric tissues, but not into ipsilateral adrenal gland or beyond Gerota's fascia.\n  3. T4 is defined as a tumour involving the ipsilateral adrenal gland or invading beyond Gerota's fascia.\n  4. N1 is defined as metastatic involvement of regional lymph nodes. 5. Archival tumour tissue sample or newly obtained core, incisional, or excisional biopsy of a tumour lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.\n\n     6\\. Have an Eastern Cooperation Oncology Group (ECOG) Performance Status of 0 to 1.\n\n     Evaluation of ECOG is to be performed within 14 days prior to the first dose of study intervention.\n\n     7\\. Have been considered suitable for curative intent surgery (partial or total nephrectomy), as evaluated by a surgeon. 8. Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150\u002F90 mm Hg.\n\n     9\\. Have adequate organ function as defined in the following table (Table 7). Specimens must be collected within 14 days prior to the start of study intervention.\n\n     10.Participants agree to the contraception guidelines outlined in section 5.1.3.2.\n\n     11.Participants who are HBsAg positive are eligible if they have received hepatitis B virus (HBV) anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.\n\n     Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.\n\n     Hepatitis B screening tests are not required unless:\n\n     Known history of HBV infection As mandated by local health authority 12.Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.\n\n     Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.\n\n     Hepatitis C screening tests are not required unless:\n\n     Known history of HCV infection As mandated by local health authority 13.HIV-infected participants must have well-controlled HIV on antiretroviral therapy (ART), defined as:\n\n  \u003C!-- -->\n\n  1. Participants on ART must have a CD4+ T-cell count ≥350 cells\u002Fmm3 at the time of screening.\n  2. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the lower limit of quantification (LLOQ) (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening\n  3. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.\n  4. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the stud\n\nExclusion Criteria:\n\n* 1\\. Has evidence of metastatic disease on screening imaging. 2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).\n\n  3\\. Has received prior systemic anti-cancer therapy including investigational agents within 3 years prior to randomization.\n\n  4\\. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.\n\nParticipants with low-risk early-stage prostate cancer either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.\n\n5\\. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. COVID-19 and influenza vaccinations are allowed provided they are not live vaccines 6. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.\n\n7\\. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug 8. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and\u002For any of its excipients, and\u002For lenvatinib, and\u002For belzutifan.\n\n9\\. Has active autoimmune disease that has required immunosuppressive systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid).\n\n10.Has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease that required steroids or has current pneumonitis\u002Finterstitial lung disease11.Has any of the following:\n\n1. A pulse oximeter reading \\\u003C92% at rest, or\n2. Requires intermittent supplemental oxygen, or\n3. Requires chronic supplemental oxygen. 12.Has an active infection requiring systemic intravenous therapy. 13.Has moderate to severe hepatic impairment (Child-Pugh B or C). 14.Concurrent active Hepatitis B (defined as HBsAg positive and\u002For detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.\n\nNote: Hepatitis B and C screening tests are not required unless:\n\n1. Known history of HBV and HCV infection\n2. As mandated by local health authority\n\n15.Has urine protein ≥1 g\u002F24 hours.\n\n1. Note: Participants with proteinuria ≥2+ (≥100 mg\u002FdL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.\n2. Note: Urine dipstick is the preferred method for testing urinary protein, however, urinalysis may be used if the use of urine dipsticks is not feasible.\n\n   16.Has had major surgery within 3 weeks prior to first dose of study interventions.\n\n   Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility 17.Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.\n\n   18.Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n\n   19.Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.\n\n   20.Has had an allogenic tissue\u002Fsolid organ transplant. 21.Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula22.Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).\n\n   23.Prolongation of QTcF interval to \\>480 ms. 24.Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.\n\n   25.Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.\n\n   26.Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib 27.Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort)",{"count":79,"type":21},150,[24],"This study is designed to evaluate the efficacy of belzutifan in combination with pembrolizumab with or without lenvatinib in the neoadjuvant setting, followed by adjuvant pembrolizumab versus adjuvant pembrolizumab alone, as treatment for participants with intermediate-high and high risk clear cell renal cell carcinoma (ccRCC).",[83],"Renal Cell Carcinoma","NOT_YET_RECRUITING","2026-05-18",{"date":87,"type":36},"2026-05-20",{"date":89,"type":21},"2026-06",{"date":91,"type":21},"2031-06",{"name":42,"class":43},14,{"id":95,"slug":96,"hasResults":11,"nctId":97,"briefTitle":98,"officialTitle":99,"acronym":100,"eligibilityCriteria":101,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":102,"targetDuration":4,"studyType":22,"phases":104,"briefSummary":105,"conditions":106,"keywords":4,"overallStatus":84,"whyStopped":4,"lastUpdateSubmitDate":108,"lastUpdatePostDateStruct":109,"startDateStruct":111,"completionDateStruct":113,"leadSponsor":115,"locationsCount":44},"100606681","phase-2-a-study-to-characterize-encorafenib-plus-cetuximab-as-rechallenge-treatment-for-braf-v600e-mutant-metastatic-colorectal-cancer-patients-after-previous-therapy-with-braf-inhibitors-based-combinations-100606681","NCT07178717","A Study to Characterize Encorafenib Plus Cetuximab as Rechallenge Treatment for BRAF V600E-mutant Metastatic Colorectal Cancer Patients After Previous Therapy With BRAF Inhibitors-based Combinations","A Phase 2, Single-Arm Study of Encorafenib Plus Cetuximab as Rechallenge Treatment of BRAF V600E-mutant Metastatic Colorectal Cancer Patients After Previous Therapy With BRAF Inhibitors-based Combinations: the RefIsh Trial","REFISH","Inclusion Criteria:\n\n1. Provision of signed and dated informed consent form.\n2. Age ≥18 years at the time of informed consent.\n3. Histologically- or cytologically confirmed mCRC that is metastatic.\n4. Presence of confirmed BRAF V600E mutation.\n5. Eligible to receive cetuximab and encorafenib per locally approved label with regard to tumor RAS status.\n6. Patients must be previously treated with at least 2 prior regimens for metastatic disease and had demonstrated progressive disease or intolerance to their last regimen. Prior standard chemotherapy must include the following agents: fluoropyrimidine in monotherapy or in combination with irinotecan and\u002For oxaliplatin with or without anti-VEGF. Combination of chemotherapy with BRAF inhibitor-containing regimen is also permitted.\n7. Patients must have received BRAF inhibitor plus anti-EGFR combinations (including but not limited to MEK or ERK inhibitors or chemotherapy) treatment for ≥ 4 months. Patients must have had complete response, partial response or stable disease \\>6 months during the BRAF inhibitor-based treatment.\n8. Patients at study enrollment should have at least 4 months interval since the last administration of BRAF inhibitors.\n9. Life expectancy \\>12 weeks, as determined by the investigator.\n10. Patients must have progressed during or within 6 months of the last chemotherapy regimen \\> Patients who received adjuvant\u002Fneoadjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant\u002Fneoadjuvant chemotherapy are permitted to count the adjuvant\u002Fneoadjuvant therapy as one regimen for advanced disease.\n11. Measurable disease according to RECIST v1.1.\n12. ECOG performance status 0-1.\n13. Adequate bone marrow function characterized by the following at screening:\n\n    1. Absolute neutrophil count (ANC) ≥1.5 x 10\\^9\u002FL.\n    2. Platelets ≥100 x 10\\^9\u002FL.\n    3. Hemoglobin ≥9.0 g\u002FdL (with or without blood transfusions).\n14. Adequate hepatic and renal function characterized by the following at screening:\n\n    1. Serum total bilirubin ≤1.5 x upper limit of normal (ULN) and \\\u003C2 mg\u002FdL. Note: Total bilirubin \\>1.5 x ULN is allowed if direct (conjugated) ≤1.5 x ULN and indirect (unconjugated) bilirubin is ≤4.25 x ULN.\n\n       Note: Participants with hyperbilirubinemia due to non-hepatic cause (e.g., hemolysis, hematoma) may be enrolled following discussion and agreement with the Sponsor medical monitor.\n    2. Alanine aminotransferase (ALT) and\u002For aspartate aminotransferase (AST) ≤2.5 x ULN, or ≤5 x ULN in the presence of liver metastases.\n    3. Adequate renal function defined by an estimated creatinine clearance ≥50 mL\u002Fmin according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance, or according to local institutional standard method.\n    4. Protein \\\u003C 2+ on dipstick urinalysis or ≤ 1.0 g in a 24-hour urine collection. All patients with ≥2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein.\n    5. Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits.\n\n    Note: Replacement treatment to achieve adequate electrolytes will be allowed.\n15. Adequate cardiac function characterized by the following at screening:\n\n    • Mean triplicate QT interval corrected for heart rate using Fridericia's formula (QTcF) value ≤480 msec.\n16. Able to take oral medications.\n17. Highly effective contraception for both male and female subjects if the risk of conception exists during and at least up to 2 months after the last study medication.\n\nExclusion Criteria:\n\n1. Treatment with another investigational drug or participation in another investigational study at enrolment or within 30 days prior to enrollment.\n2. Patient unable to comply with the study protocol owing to psychological, social (lack of social support or social exclusion) or geographical reasons.\n3. Patient is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.\n4. Known history of chronic pancreatitis.\n5. Tumors with microsatellite instability or mismatch repair deficiency if they have not received a PD1\u002FPDL1 inhibitor-based treatment, unless medical contraindication.\n6. History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months before the enrollment in the study.\n7. Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:\n\n   1. History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft \\[CABG\\], coronary angioplasty or stenting) ≤ 6 months prior to start of study treatment.\n   2. Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and\u002For conduction abnormality ≤ 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia.\n8. Impaired hepatic function, defined as Child-Pugh class B or C.\n9. Known history of human immunodeficiency virus (HIV), active hepatitis B virus (HBV) infection or active hepatitis C virus (HCV) infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients with past exposure to HBV are also eligible for the study provided they are negative for HBV DNA.\n10. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study.\n\n    Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and the enrollment in the study.\n11. Subjects with leptomeningeal carcinomatosis.\n12. Impaired gastrointestinal (GI) function or disease that may significantly alter the absorption of encorafenib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).\n13. Knowledge of any other disease or medication that may interfere with study treatment.\n14. Presence of any contraindication with regard to the study drugs as specified in the corresponding SmPCs.\n15. Patients who achieved progression disease as best response while receiving BRAF inhibitor previously.",{"count":103,"type":21},25,[24],"This is an open-label, unicentre, single-arm Phase 2 study of encorafenib and cetuximab as rechallenge treatment in patients with BRAF V600E-mutant metastatic colorectal cancer after previous therapy with BRAF inhibitors-based combinations.\n\nThe study aims to evaluate the antitumor activity of encorafenib plus cetuximab as a rechallenge strategy measured by progression-free survival rate at 4 months.\n\nEligible patients (a total of 25) will receive encorafenib 300 mg (four 75 mg capsules) once daily (q.d) in 28-day cycles plus intravenous cetuximab at 500 mg\u002Fm2 every 2 weeks (Q2W). Treatment will be administered until progression, unacceptable toxicity, patient request, physician's decision or subsequent anticancer therapy.",[107],"Colo-rectal Cancer","2025-09-10",{"date":110,"type":36},"2025-09-17",{"date":112,"type":21},"2025-10",{"date":114,"type":21},"2028-08",{"name":42,"class":43},{"id":117,"slug":118,"hasResults":11,"nctId":119,"briefTitle":120,"officialTitle":121,"acronym":122,"eligibilityCriteria":123,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":124,"targetDuration":4,"studyType":22,"phases":126,"briefSummary":127,"conditions":128,"keywords":132,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":137,"lastUpdatePostDateStruct":138,"startDateStruct":140,"completionDateStruct":142,"leadSponsor":144,"locationsCount":44},"100564548","phase-2-evaluation-of-a-pragmatic-approach-to-adoptive-cell-therapy-act-using-an-il2-analog-anv419-vs-high-dose-il2-after-tumor-infiltrating-lymphocytes-til-therapy-in-patients-with-melanoma-nsclc-and-cervical-cancer-pragmatil-100564548","NCT06630611","Evaluation of a Pragmatic Approach to Adoptive Cell Therapy (ACT) Using an IL2 Analog (ANV419) vs High Dose IL2 After Tumor Infiltrating Lymphocytes (TIL) Therapy in Patients With Melanoma, NSCLC and Cervical Cancer (PragmaTIL)","Phase II Randomized Study Evaluating a Pragmatic Approach to Adoptive Cell Therapy (ACT) Using an IL2 Analog (ANV419) vs High Dose IL2 After Tumor Infiltrating Lymphocytes (TIL) Therapy in Patients With Melanoma, NSCLC and Cervical Cancer","PragmaTIL","Inclusion Criteria:\n\n1. Patients must have histologically or cytologically proven metastatic or unresectable cutaneous melanoma, NSCLC, or cervical cancer. The disease must have progressed to at least one standard systemic anticancer therapy, regardless whether in the adjuvant or metastatic setting, or the patient is unable\u002Funwilling to receive standard therapy. Patients who are receiving an anticancer treatment post-progression are also eligible to be included, at the investigator's discretion, always respecting the wash-out period for starting NMA-LD chemotherapy.\n2. Patients must have at least one adequate lesion (primary tumor or metastasis) for resection or biopsy (with minimal morbidity, preferentially using imaging-guided minimally invasive procedures) for TIL generation.\n\n   Note: If this lesion was previously irradiated, the lesion must have demonstrated progression prior to resection\u002Fbiopsy.\n3. Patients must have a remaining measurable disease as defined by RECIST v. 1.1 criteria following tumor resection\u002Fbiopsy for TIL manufacturing.\n\n   Note: Lesions previously irradiated should not be selected as target lesions unless there has been demonstrated progression in those lesions.\n4. Patient must be at least 18 years old at the tissue procurement visit.\n5. Patient must understand and voluntarily sign an informed consent document before any study-related assessments\u002Fprocedures being conducted.\n6. Patient must be able and willing to comply to the study visit schedule and protocol requirements.\n7. Patients must have a clinical performance of Eastern Cooperative Oncology Group 0 or 1.\n8. Patients are considered medically fit enough to undergo all study procedures and interventions and adequate hematological, renal, and hepatic functions defined by:\n\n   1. Haemoglobin ≥9.0 g\u002FdL.\n   2. An absolute neutrophil count ≥ 1.5x10E9\u002FL without the support of filgrastim.\n   3. Platelets ≥100x10E9\u002FL.\n   4. PT and aPTT ≤1.5 x ULN (unless receiving therapeutic anticoagulation).\n\n      \\- subjects receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose.\n   5. AST or ALT ≤3 x ULN. Patients with liver metastases must have AST and ALT ≤5.0 x ULN.\n   6. Total bilirubin \\\u003C2 mg\u002FdL. Patients with Gilbert's Syndrome must have a total bilirubin ≤3.0 mg\u002FdL.\n   7. Serum creatinine \\\u003C1.5 mg\u002FdL or measured creatinine clearance ≥50 ml\u002Fmin calculated using the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female)\u002F72 × (serum creatinine in mg\u002FdL).\n9. Patients with documented LVEF of ≥ 45%.\n10. Patients with documented FEV1, FVC and DLCO ≥ 50% tested by a pulmonary function test.\n11. Patients must be seronegative for HIV antibody (patients who are HIV seropositive may be less responsive and more susceptible to toxicities related to this experimental treatment since they may have a decreased immune competence).\n12. Patients must be seronegative for active hepatitis B (defined as having a negative hepatitis B surface antigen \\[HBsAg\\] test), and seronegative for hepatitis C antibody. Patients with a history of hepatitis B virus (HBV) infection and having a negative HBsAg test and a positive antibody to hepatitis B surface antigen (HBsAg) are eligible. Patients with the hepatitis C antibody test positive are eligible only if tested for the presence of antigen by RT-PCR and be HCV RNA negative.\n13. Life expectancy ≥3 months.\n14. Patients who are of childbearing potential (postmenarcheal who has not reached a postmenopausal state and has not undergone surgical sterilization) or have partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 6 months after the last dose of IL-2.\n15. Female participants: a female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:\n\n    1. Women of non-childbearing potential (WONCBP).\n    2. Women of childbearing potential (WOCBP), who:\n\n    i. Agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year from screening until 6 months after the infusion of the TIL product. Examples of contraceptive methods with a failure rate of \\\u003C1% per year include bilateral tubal occlusion, male sterilization, and copper intrauterine devices.\n\n    ii. Have a negative pregnancy test (blood) within one week before the first study treatment administration (applicable to premenopausal women and women ≤2 years after the start of menopause (menopause is defined as amenorrhea for \\\u003C2 years).\n\n    iii. Refrain for donating ovules during the study\n16. Male Participants: during the treatment period and for at least 2 months after the last dose of study treatment, agreement to:\n\n    1. Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom or a contraceptive method that result in a failure rate of \\\u003C1% per year, with partners who are WOCBP.\n    2. Refrain from donating sperm during the study.\n    3. Inform if his partner gets pregnant during this time.\n17. Any toxicity related to prior systemic therapy must have recovered to grade 1 or less according to NCI-CTCAE v5.0 at least 4 weeks before enrollment, except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy, and Grade ≤2 peripheral neuropathy.\n\n    Note: Other Grade 2 AEs that are deemed clinically insignificant by treating physician and in consultation with Medical Monitor are permitted.\n18. Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.\n\nExclusion Criteria:\n\n1. Patients with more than two brain metastases. Note: Patients with brain metastases \\> 1cm in diameter or perilesional edema on MRI scan must be definitively-treated and stable for at least 4 weeks, and the patient must not require corticosteroid treatment \\>10 mg prednisone or equivalent per day to be considered for enrollment;\n2. Patients with symptomatic brain metastasis.\n3. Patients with leptomeningeal carcinomatosis.\n4. Patients with an active concurrent or history within the past 3 years of invasive malignancy, except for non-melanoma skin cancer, cervical and bladder carcinoma in situ, good prognosis ductal carcinoma in situ of the breast, or prostate carcinoma that is in remission under androgen deprivation therapy for \\>2 years. Other exceptions may apply and require discussion between the Investigator and the Medical Monitor.\n5. Patients with an active systemic infection requiring anti-infective treatment within 14 days before preparative lymphodepleting therapy.\n6. Patients with active hepatitis B or hepatitis C.\n7. Patients with active autoimmune disease requiring immunosuppressive treatments.\n8. Patients with a history of organ or bone marrow transplantation.\n9. Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).\n10. Patients requiring regular treatment with steroids at a dose higher than prednisone 10 mg\u002Fday (or equivalent).\n\n    Note: use of inhaled, topical steroids and use of systemic physiologic corticosteroid replacement therapy are permitted.\n11. Patients with current or history within the last 6 months, as determined by the Investigator, of clinically significant, progressive, and\u002For uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.\n12. Patients with a history of coronary revascularization or ischemic symptoms within 6 months of first dose of NMA-LD chemotherapy.\n13. History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin).\n14. Patients with allergies to any of the compounds included in any of the treatment products.\n15. Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses.\n16. Patients who have received any approved anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy within 4 weeks before preparative lymphodepleting therapy.\n\n    a) Exception: palliative radiotherapy for bone metastasis \\>2 weeks before preparative lymphodepleting therapy, denosumab, bisphosphonates, androgen-deprivation therapy for prostate cancer and hormonal therapy for breast cancer.\n17. Patients who have received any non-cytotoxic drug and molecular targeted therapy within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).\n18. Patients who have received any investigational agent within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).\n19. Patients who have received a live, attenuated vaccination within the 4 weeks before lymphodepleting therapy.\n20. Patients who have undergone major surgery in the previous 3 weeks before lymphodepleting therapy.\n21. Patients who have previously received any investigational cell or gene therapies.\n22. Women of childbearing potential who are pregnant or breastfeeding.\n23. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.",{"count":125,"type":21},40,[24],"Background:\n\nThe presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity.\n\nTIL-based ACT (Adoptive cell therapy using tumor-infiltrating lymphocytes product) is a modality of ACT used to treat patients with multiple types of cancer and it consists in the adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes obtained from tumor resection or tumor biopsies in patients following a non-myeloablative lymphodepleting (NMA-LD) chemotherapy. Ex vivo expansion of TIL relies on the non-specific expansion of lymphocytes present in tumor single cell suspensions or tumor fragments in high dose IL-2.\n\nAlthough proven efficacy in selected, the HD-IL-2 use remains relatively restricted due to toxicity. Due to the short serum half-life and the need to achieve an immune-modulatory effect in the tissues, IL-2 must be given in doses that induce severe systemic toxicities, including capillary leak syndrome (CLS), pulmonary edema, hypotension, acute renal insufficiency, and rarely myocarditis, limiting its applicability in cancer. Studies comparing HD-IL-2 with lower doses both in renal cell carcinoma and metastatic melanoma to minimize toxicity demonstrated the superiority of the high dose regimens in both diseases. These drawbacks of HD-IL-2 use encouraged the development of improved IL-2-based biologic agents with higher selectivity for effector immune cell subsets, reduced toxicity, and prolonged half-life.\n\nANV419 is a novel IL-2 agent, which has been developed as a preferentially IL-2Rβγ directed fusion protein with a longer half-life. It has shown high effector selectivity and a favorable safety profile in preclinical testing, including in nonhuman primates, and it has been investigated in an ongoing open-label, dose-escalation Phase I Study in multiple tumor types. he safety profile of ANV419 is characterized by pyrexia, nausea, vomiting, ALT\u002FAST changes and CRS in some patients. Most events are low grade and self-limiting and manageable with standard supportive care. ANV419 was well-tolerated by most patients. No patient discontinued treatment due to treatment related AE.\n\nTaking all the previous information into account, the primary objectives of this study are:\n\n1. To determine whether TIL-ACT using the IL-2 analog ANV419 reduces the mean number of predefined grade ≥3 relevant adverse events related to interleukin use (based on Common Terminology Criteria for Adverse Events v5.0 - CTCAE v5.0) compared to TIL-ACT using HD-IL-2.\n2. To determine whether TIL-ACT using the IL-2 analog improves patient´s reported outcomes (PRO) compared to TIL-ACT using HD-IL-2",[129,130,131],"Melanoma","Non Small Cell Lung Cancer","Cervical Cancer",[133,134,135,136],"Immune checkpoint blockade (ICB) resistant tumors","Tumor-Infiltrating Lymphocyte","Adoptive Cell Therapy","Interleukin-2 (IL-2)","2025-01-24",{"date":139,"type":36},"2025-01-28",{"date":141,"type":36},"2025-01-15",{"date":143,"type":21},"2029-09",{"name":42,"class":43},{"id":146,"slug":147,"hasResults":11,"nctId":148,"briefTitle":149,"officialTitle":149,"acronym":150,"eligibilityCriteria":151,"healthyVolunteers":11,"sex":17,"minAge":152,"maxAge":4,"enrollmentInfo":153,"targetDuration":4,"studyType":22,"phases":154,"briefSummary":155,"conditions":156,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":159,"lastUpdatePostDateStruct":160,"startDateStruct":162,"completionDateStruct":164,"leadSponsor":166,"locationsCount":44},"100566079","phase-2-a-phase-2-pilot-study-to-evaluate-the-safety-and-the-anti-tumour-activity-of-the-myc-inhibitor-omo-103-administered-intravenously-in-patients-with-advanced-high-grade-osteosarcoma-100566079","NCT06650514","A Phase 2 Pilot Study to Evaluate the Safety and the Anti-Tumour Activity of the Myc Inhibitor OMO-103 Administered Intravenously in Patients With Advanced High-Grade Osteosarcoma","Osteomyc","Inclusion Criteria:\n\n1. Provision of signed and dated informed consent form.\n2. Age ≥12 years at time of informed consent.\n3. Histologically proven, advanced high-grade osteosarcoma not suitable for local treatments with curative intent\n4. Confirmed disease progression by radiological report to at least one line of standard chemotherapy containing cisplatin and anthracycline, and no more than 2 previous lines.\n5. Measurable disease as per RECIST v1.1 criteria and documented by CT\u002FMRI (Appendix 1 - RECIST Response Criteria). NOTE: Lesions to be used as measurable disease for the purpose of response assessment must either:\n\n   1. not reside in a field that has been subjected to prior radiotherapy, or\n   2. have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrolment.\n6. Provision of a newly obtained tumour biopsy (either from the primary tumour or from metastases) during screening and on-treatment from all patients \\>16 years of age. Notes:\n\n   * The identified lesion to be biopsied should not have been previously irradiated and should not be the only lesion being used as a measurable-disease target lesion for objective response assessment. Patients must have tumour lesions that can be accessible for biopsy with acceptable clinical risk in the judgement of the Investigator.\n   * In case a patient has had a tumour biopsy in the previous 6 months and a paraffin block is available, a new biopsy does not need to be done at Screening (if they have received no treatment after biopsy).\n7. Documented progression on or following the last line of therapy.\n8. ECOG performance status 0-2 (Appendix 2 - Performance Status Criteria).\n9. Life expectancy of ≥ 12 weeks as estimated by the treating physician.\n10. Resolution of all acute, reversible toxic effects of prior therapy or surgical procedure to Grade ≤1 (except alopecia and peripheral neuropathy to Grade ≤2).\n11. Adequate organ function.\n12. If not postmenopausal or surgically sterile, female patients and female sexual partners of male patients must be willing to use at least one highly effective method of birth control (hormonal contraception, IUD, abstinence, condom) for at least a menstrual cycle before and for 3 months after last study drug administration.\n\nExclusion Criteria:\n\n1. Treatment with systemic anti-cancer therapy within three weeks prior to study drug administration for chemotherapy and 5 half-lives for targeted therapies.\n2. Radiation therapy within four weeks prior to study entry. Localised palliative radiotherapy to nontarget lesions is allowed\n3. Low-grade osteosarcoma, parosteal, or periosteal osteosarcoma.\n4. Prior history of other malignancies other than osteosarcoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 2 years.\n5. Non-malignant systemic disease including cerebrovascular accident, unstable angina pectoris, unstable atrial fibrillation, unstable cardiac arrhythmia, myocardial infarction in the last six months, New York Heart Association (NYHA) Class III or IV heart failure (Appendix 5 - New York Heart Association Criteria).\n6. Patients with active uncontrolled infection or known to be serologically positive for human immunodeficiency virus (HIV), hepatitis B (except after vaccination) or hepatitis C infection. Investigators may test as per their discretion.\n7. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.\n8. Patients with symptomatic or unstable central nervous system primary tumour or metastases and\u002For sarcomatous meningitis\n9. Live vaccine in the last four weeks.\n10. Current participation in another interventional therapeutic trial.\n11. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.\n12. Knowledge of any other disease or medication that may interfere with study treatment.\n13. Patients with known allergies or hypersensitivity reactions to the active substance or to any of its excipients\n14. Patient unable to comply with the study protocol owing to psychological, social (lack of social support or social exclusion) or geographical reasons.","12 Years",{"count":5,"type":21},[24],"This is an open-label, unicentric, single-arm Phase 2 pilot study to serve as a proof-of-concept of OMO-103 safety and activity in patients with advanced high-grade osteosarcoma.\n\nPatients will be treated at the RP2D (6.5 mg\u002Fkg as a weekly IV infusion) of OMO-103 to estimate anti-tumour activity and further characterise the safety, tolerability, PK, and PD of OMO-103 in advanced high-grade osteosarcoma patients. Ten (10) evaluable patients will be enrolled. At least 30% of patients will be \\\u003C18 years old. The first three patients 12-15 years of age will undergo additional safety monitoring.\n\nPatients will be treated until progression by RECIST v1.1 or intolerable toxicity.",[157,158],"Osteosarcoma","Osteosarcoma in Children","2025-01-08",{"date":161,"type":36},"2025-01-10",{"date":163,"type":36},"2024-12-27",{"date":165,"type":21},"2026-12",{"name":42,"class":43},{"id":168,"slug":169,"hasResults":11,"nctId":170,"briefTitle":171,"officialTitle":172,"acronym":173,"eligibilityCriteria":174,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":175,"targetDuration":4,"studyType":22,"phases":177,"briefSummary":178,"conditions":179,"keywords":181,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":185,"lastUpdatePostDateStruct":186,"startDateStruct":188,"completionDateStruct":190,"leadSponsor":192,"locationsCount":44},"100547717","phase-2-combination-therapy-for-braf-v600e-metastatic-crcm-100547717","NCT06411600","Combination Therapy for BRAF-V600E Metastatic CRCm","Bevacizumab Plus encoRAfenib-cetuximab in BRAF-V600E Mutated Metastatic Colorectal Cancer, a Phase II Study With a Safety lead-in Cohort, the BRAVE Trial","BRAVE","Inclusion Criteria:\n\n* Provision of signed and dated informed consent form.\n* Age ≥18 years at time of informed consent.\n* Histologically- or cytologically-confirmed mCRC that is metastatic.\n* Presence of BRAF V600E mutation in tumor tissue previously determined according to the guidelines of each center, any time point before the enrollment in the study.\n* Microsatellite stability must be confirmed according to the guidelines of each center, any time point before the enrollment in the study.\n* Eligible to receive cetuximab per locally approved label with regard to tumor RAS status, any time point before the enrollment in the study.\n* Progression of disease after 1 or 2 prior regimens in the metastatic setting.\n* Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1.\n* ECOG PS of 0 or 1.\n* Adequate bone marrow function characterized by the following at screening:\n\n  1. Absolute neutrophil count (ANC) ≥1.5 x 109\u002FL\n  2. Platelets ≥100 x 109\u002FL\n  3. Hemoglobin ≥9.0 g\u002FdL (with or without blood transfusions).\n* Adequate hepatic and renal function characterized by the following at screening:\n\n  1. Serum total bilirubin ≤1.5 x upper limit of normal (ULN) and \\\u003C2 mg\u002FdL. Note: Total bilirubin \\>1.5 x ULN is allowed if direct (conjugated) ≤1.5 x ULN and indirect (unconjugated) bilirubin is ≤4.25 x ULN. Note: Participants with hyperbilirubinemia due to non-hepatic cause (e.g., hemolysis, hematoma) may be enrolled following discussion and agreement with the Sponsor medical monitor.\n  2. Alanine aminotransferase (ALT) and\u002For aspartate aminotransferase (AST) ≤2.5 x ULN, or ≤5 x ULN in the presence of liver metastases.\n  3. Adequate renal function defined by an estimated creatinine clearance ≥50 mL\u002Fmin according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance, or according to local institutional standard method.\n  4. Protein \\\u003C 2+ on dipstick urinalysis or ≤ 1.0 g in a 24-hour urine collection. All patients with ≥2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein.\n  5. Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits.\n\nNote: Replacement treatment to achieve adequate electrolytes will be allowed.\n\n* Adequate cardiac function characterized by the following at screening:\n\n  a.Mean triplicate QT interval corrected for heart rate using Fridericia's formula (QTcF) value ≤480 msec.\n* Able to take oral medications.\n* Highly effective contraception for both male and female subjects if the risk of conceptions exists during and at least up to 6 months after the last medication. See 10.4. Appendix 4.\n\nExclusion Criteria:\n\n* Treatment with another investigational drug or participation in another investigational study at enrolment or within 30 days prior to enrolment.\n* Patient unable to comply with the study protocol owing to psychological, social (lack of social support or social exclusion) or geographical reasons.\n* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.\n* Prior history of hypertensive crisis or hypertensive encephalopathy.\n* Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.\n* Evidence of bleeding diathesis or clinically significant coagulopathy (in the absence of therapeutic anticoagulation).\n* Patients with history of pulmonary hemorrhage\u002Fhemoptysis (\\>1\u002F2 teaspoon red blood) within 6 months prior to Cycle 1, Day 1.\n* Known history of acute or chronic pancreatitis.\n* Tumors with microsatellite instability or mismatch repair deficiency.\n* History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention. (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months before the enrollment in the study.\n* Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:\n\n  1. History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft \\[CABG\\], coronary angioplasty or stenting) ≤ 6 months prior to start of study treatment.\n  2. Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and\u002For conduction abnormality ≤ 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia.\n* Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy.\n* Impaired hepatic function, defined as Child-Pugh class B or C.\n* Known history of human immunodeficiency virus (HIV), active hepatitis B virus (HBV) infection or active hepatitis C virus (HCV) infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients with past exposure to HBV are also eligible for the study provided they are negative for HBV DNA.\n* Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and the enrollment in the study.\n* Subjects with leptomeningeal carcinomatosis.\n* Impaired gastrointestinal (GI) function or disease that may significantly alter the absorption of encorafenib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).\n* Concurrent or previous other malignancy within 5 years of study entry without Sponsor approval, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy.\n* History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary embolism.\n* Knowledge of any other disease or medication that may interfere with study treatment.\n* Known severe hypersensitivity reactions to monoclonal anti-bodies or BRAF inhibitors.\n* Known hypersensitivity to any of encorafenib, cetuximab or bevacizumab-bvzr active ingredients or their excipients.",{"count":176,"type":21},94,[24],"The BRAVE is a phase II clinical trial aimed at evaluating the efficacy of the combination therapy of encorafenib, cetuximab, and bevacizumab in patients with metastatic colorectal cancer (CRC) harboring the BRAF-V600E mutation. This mutation is present in about 8-10% of CRC cases and is associated with poor prognosis and limited treatment options. The rationale behind this trial stems from preclinical studies suggesting that the overexpression and activation of vascular endothelial growth factor A (VEGFA) may contribute to resistance to BRAF inhibitors (BRAFi) in CRC. Thus, the trial hypothesizes that adding bevacizumab, an anti-angiogenic agent targeting VEGFA, to the combination of encorafenib and cetuximab may delay acquired resistance, leading to improved progression-free survival.\n\nThe primary objective of the BRAVE is to evaluate the antitumor activity of the encorafenib-cetuximab-bevacizumab combination in patients who have experienced disease progression after one or two chemotherapy regimens for BRAF V600E-mutant metastatic CRC. This activity will be assessed based on the confirmed progression-free survival rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.",[180],"Metastatic Colorectal Cancer",[182,183,184],"Encorafenib","Cetuximab","Bevacizumab","2024-11-06",{"date":187,"type":36},"2024-11-08",{"date":189,"type":36},"2024-05-17",{"date":191,"type":21},"2029-05-01",{"name":42,"class":43},{"id":194,"slug":195,"hasResults":11,"nctId":196,"briefTitle":197,"officialTitle":198,"acronym":199,"eligibilityCriteria":200,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":201,"targetDuration":4,"studyType":22,"phases":202,"briefSummary":204,"conditions":205,"keywords":208,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":185,"lastUpdatePostDateStruct":211,"startDateStruct":213,"completionDateStruct":215,"leadSponsor":217,"locationsCount":44},"100450129","early-phase-1-assessment-of-the-safety-and-tolerability-of-ex-vivo-next-generation-neoantigen-selected-tumor-infiltrating-lymphocyte-til-therapy-in-advanced-epithelial-tumors-and-immune-checkpoint-blockade-icb-resistant-solid-tumors-100450129","NCT05141474","Assessment of the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors","A Phase I Study to Assess the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors","NEXTGENTIL-ACT","Inclusion Criteria in the pretreatment phase:\n\n1. Patients must have histologically or cytologically proven metastatic or unresectable solid tumors. The disease must have progressed to at least one standard therapy (including at least one prior line with ICB for the group of patients with tumors where ICB is approved), or the patient is unable\u002Funwilling to receive standard therapy or no standard therapy exists for a particular disease.\n2. Patients must have at least one adequate lesion (primary tumor or metastasis) for resection or biopsy for TIL generation with minimal morbidity (preferentially using imaging-guided minimally invasive procedures).\n\n   Note: If this lesion was previously irradiated, the lesion must have demonstrated progression prior to resection\u002Fbiopsy.\n3. Patient must be at least 18 years old at the tissue procurement visit.\n4. Patient must understand and voluntarily sign an informed consent document before any study-related assessments\u002Fprocedures being conducted.\n5. Patient must be able and willing to comply to the study visit schedule and protocol requirements.\n6. Patients must have a clinical performance of Eastern Cooperative Oncology Group 0 or 1.\n7. Patients are considered medically fit enough by investigator to undergo all study procedures and interventions.\n8. Patients with documented left ventricular ejection fraction (LVEF) of ≥45%.\n9. Patients with documented forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) ≥50% tested by a pulmonary function test.\n10. Patients must be seronegative for HIV antibody (patients who are HIV seropositive may be less responsive and more susceptible to toxicities related to this experimental treatment since they may have a decreased immune competence).\n11. Patients must be seronegative for active hepatitis B (defined as having a negative hepatitis B surface antigen \\[HBsAg\\] test), and seronegative for hepatitis C (HCV) antibody. Patients with a history of hepatitis B virus (HBV) infection and having a negative HBsAg test and a positive antibody to hepatitis B surface antigen (HBsAg) are eligible. Patients with the hepatitis C antibody test positive are eligible only if tested for the presence of antigen by RT-PCR and be HCV RNA negative.\n12. Life expectancy ≥6 months.\n13. Patients who are of childbearing potential (postmenarcheal who has not reached a postmenopausal state and has not undergone surgical sterilization) or have partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 6 months after the last dose of IL-2.\n\nInclusion Criteria in the treatment phase:\n\n1. The disease must have progressed to the last standard therapy, including at least one prior line with ICB for the group of patients with tumors where ICB is approved, and no subsequent approved therapy is available, or the patients are unable\u002Funwilling to receive standard therapy, or no standard therapy exists for a particular disease.\n2. Patients must have a remaining measurable disease as defined by RECIST v. 1.1 criteria following tumor resection\u002Fbiopsy for NEXTGEN-TIL manufacturing.\n\n   Note: Lesions previously irradiated should not be selected as target lesions unless there has been demonstrated progression in those lesions.\n3. Patients must understand and voluntarily sign an informed consent document before any study-related assessments\u002Fprocedures being conducted.\n4. Patients must be able and willing to comply with the study visit schedule and protocol requirements.\n5. Patients must have a clinical performance of Eastern Cooperative Oncology Group (ECOG) 0 or 1.\n6. Patients are considered medically fit enough to undergo all study procedures and interventions and adequate hematological, renal and hepatic functions defined by:\n\n   1. Haemoglobin ≥9.0 g\u002FdL.\n   2. An absolute neutrophil count ≥1000\u002Fmm3 without the support of filgrastim.\n   3. Platelets ≥ 100 x10⁹ \u002Fmm3.\n   4. PT and aPTT ≤1.5 x upper limit of normal (ULN, unless receiving therapeutic anticoagulation). Subjects receiving therapeutic anticoagulation (such as low-molecularweight heparin or warfarin) should be on a stable dose.\n   5. AST or ALT ≤3 x ULN. Patients with liver metastases must have AST and ALT ≤5.0 x ULN.\n   6. Total bilirubin \\\u003C2 mg\u002FdL. Patients with Gilbert's Syndrome must have a total bilirubin ≤3.0 mg\u002FdL.\n   7. Serum creatinine \\\u003C1.5 mg\u002FdL or measured creatinine clearance ≥50 ml\u002Fmin calculated using the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female)\u002F72 × (serum creatinine in mg\u002FdL).\n7. Patients must be seronegative for HIV antibody.\n8. Patients must be seronegative for active hepatitis B (defined as having a negative hepatitis B surface antigen \\[HBsAg\\] test), and seronegative for hepatitis C antibody. Patients with a history of hepatitis B virus (HBV) infection and having a negative HBsAg test and a positive antibody to hepatitis B surface antigen (HBsAg) are eligible. Patients with the hepatitis C antibody test positive are eligible only if tested for the presence of antigen by RT-PCR and be HCV RNA negative.\n9. Life expectancy ≥3 months.\n10. Patients who are of childbearing potential (postmenarcheal who has not reached a postmenopausal state and has not undergone surgical sterilization) or have partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 6 months after the last dose of IL-2.\n11. Female participants: a female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:\n\n    1. Women of non-childbearing potential (WONCBP).\n    2. Women of childbearing potential (WOCBP), who:\n\n    i. Agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year from screening until 6 months after the infusion of the NEXTGEN-TIL product. Examples of contraceptive methods with a failure rate of \\\u003C1% per year include bilateral tubal occlusion, male sterilization, and copper intrauterine devices.\n\n    ii. Have a negative pregnancy test (blood) within one week before the first study treatment administration (applicable to premenopausal women and women ≤2 years after the start of menopause (menopause is defined as amenorrhea for \\\u003C2 years).\n12. Male Participants: during the treatment period and for at least 2 months after the last dose of study treatment, agreement to:\n\n    1. Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom or a contraceptive method that result in a failure rate of \\\u003C1% per year, with partners who are WOCBP.\n    2. Refrain from donating sperm during the study.\n    3. Inform if his partner gets pregnant during this time.\n13. Any toxicity related to prior systemic therapy must have recovered to grade 1 or less according to NCI-CTCAE v5.0 at least 4 weeks before treatment enrollment, except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy, and Grade ≤2 peripheral neuropathy.\n\n    Note: Other Grade 2 AEs that are deemed clinically insignificant by treating physician and in consultation with Medical Monitor are permitted.\n14. Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.\n\nExclusion Criteria (any phase):\n\n1. Patients with symptomatic and\u002For untreated brain metastases. Note: Patients with definitively-treated brain metastases will be considered for enrollment after discussion with Medical Monitor; if, prior to the start of NMA-LD the patient is clinically stable for ≥3 months, there are no new brain lesions via magnetic resonance imaging (MRI) post-treatment, and the patient does not require corticosteroid treatment \\>10 mg prednisone or equivalent per day.\n2. Patients with leptomeningeal carcinomatosis.\n3. Patients with an active concurrent or history within the past 3 years of invasive malignancy, except for non-melanoma skin cancer, cervical and bladder carcinoma in situ, good prognosis ductal carcinoma in situ of the breast, or prostate carcinoma that is in remission under androgen deprivation therapy for \\> 2 years. Other exceptions may apply and require discussion between the Investigator and the Medical Monitor.\n4. Patients with an active systemic infection requiring anti-infective treatment within 14 days before preparative lymphodepleting therapy.\n5. Patients with active hepatitis B or hepatitis C.\n6. Patients with active autoimmune disease requiring immunosuppressive treatments.\n7. Patients with a history of organ or bone marrow transplantation.\n8. Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).\n9. Patients requiring regular treatment with steroids at a dose higher than prednisone 10 mg\u002Fday (or equivalent).\n\n   Note: use of inhaled, topical steroids and use of systemic physiologic corticosteroid replacement therapy are permitted.\n10. Patients with current or history within the last 6 months, as determined by the Investigator, of clinically significant, progressive, and\u002For uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.\n11. Patients with a history of coronary revascularization or ischemic symptoms.\n12. History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin)\n13. Patients with allergies to any of the compounds included in any of the treatment products.\n14. Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses.\n15. Patients who have received any approved anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy within 4 weeks before preparative lymphodepleting therapy. Exception: palliative radiotherapy for bone metastasis \\>2 weeks before preparative lymphodepleting therapy, denosumab, bisphosphonates, androgen deprivation therapy for prostate cancer and hormonal therapy for breast cancer.\n16. Patients who have received any non-cytotoxic drug and molecular targeted therapy within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).\n17. Patients who have received any investigational agent within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).\n18. Patients who have received a live, attenuated vaccination within the 4 weeks before lymphodepleting therapy.\n19. Patients who have undergone major surgery in the previous 3 weeks before lymphodepleting therapy.\n20. Patients who have previously received any investigational cell or gene therapies.\n21. Women of childbearing potential who are pregnant or breastfeeding.\n22. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.",{"count":5,"type":21},[203],"EARLY_PHASE1","Background:\n\nThe presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity.\n\nAdoptive cell therapy using tumor-infiltrating lymphocytes product (TIL-ACT) is a well-established combination therapy currently under study in several world reference centers, using an autologous cell product without genetic modifications. This cell product consists of tumor-infiltrating lymphocytes (TIL), which are collected from the patient and expanded in the lab under specific conditions to enhance its antitumoral efficacy before reinfusion in the same patient. However, this cell product alone does not achieve adequate efficacy, and a combination of both previous non-myeloablative lymphodepleting (NMA-LD) chemotherapy and subsequent cytokine therapy (specifically IL-2) is needed to support the expansion of the infused cells.\n\nThe investigators hypothesize that TILs enriched for neoantigen recognition are superior to unselected TILs at mediating tumor regression in patients with epithelial tumors and even other solid tumors where immune checkpoint blockade (ICB) is approved and used as part of standard therapy. The investigators propose to manufacture a T-cell product composed of TILs that are selected based on their ability to recognize patient-specific neoantigens and to use these to treat patients with metastatic, refractory, epithelial cancers, as well as ICB-resistant solid tumors. Furthermore, it also proposed to study the tumor and T cells at baseline and after treatment to investigate whether specific phenotypic and functional traits may be associated with clinical outcome.\n\nPrimary objective:\n\nTo evaluate the safety and the tolerability of ex vivo next generation neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) in patients with metastatic or unresectable epithelial tumors and immune checkpoint blockade (ICB) resistant solid tumors.\n\nSecondary objectives:\n\n* To determine the success in producing active specific TILs from our target patients.\n* To evaluate the initial clinical activity of the NEXTGEN-TIL products in our target patients.",[206,207],"Epithelial Tumors, Malignant","Malignant Solid Tumor",[209,210,135],"Immune checkpoint blockade resistant tumors","Tumor-infiltrating Lymphocyte",{"date":212,"type":36},"2024-11-07",{"date":214,"type":36},"2021-10-28",{"date":216,"type":21},"2027-01-01",{"name":42,"class":43},{"id":219,"slug":220,"hasResults":11,"nctId":221,"briefTitle":222,"officialTitle":223,"acronym":224,"eligibilityCriteria":225,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":226,"targetDuration":4,"studyType":22,"phases":228,"briefSummary":229,"conditions":230,"keywords":232,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":236,"lastUpdatePostDateStruct":237,"startDateStruct":239,"completionDateStruct":241,"leadSponsor":243,"locationsCount":244},"100344623","phase-2-a-modular-multi-basket-trial-to-improve-personalized-medicine-in-cancer-patients-basket-of-baskets-100344623","NCT03767075","A Modular Multi-Basket Trial to Improve Personalized Medicine in Cancer Patients (Basket of Baskets)","Basket of Baskets: A Modular, Open-label, Phase II, Multicentre Study To Evaluate Targeted Agents in Molecularly Selected Populations With Advanced Solid Tumours","BoB","Eligibilty Criteria (PART A - iPROFILER)\n\nInclusion Criteria:\n\n1. Subjects must have histologically or cytologically confirmed malignancy that is metastatic or unresectable, who have progressed to standard therapy, who are receiving a standard anticancer treatment, but no subsequent approved treatment would be available upon progression, who are unable to receive standard therapy, or for whom standard therapy does not exist.\n2. Patient must have ECOG performance status of 0 or 1.\n3. Subjects must be 18-year-old or older.\n4. Subjects must have measurable disease according to RECIST 1.1.\n5. Subjects must have enough tumour tissue for molecular analysis.\n\n   1. Subjects providing formalin-fixed paraffin embedded tissue (FFPE) must provide a minimum amount of tissue ranging from 28 to 36 slides depending on the sample tumour cellularity. If there is not enough archival tissue to meet this criterion, the patient must undergo a tumour biopsy.\n   2. Subjects providing fresh frozen tissue must provide 5 core biopsies or equivalent.\n\n      Fresh frozen tissue must be preferentially collected from a tumour biopsy; hence, subjects must have disease amenable to be biopsied. Otherwise, the patient should have fresh frozen tumour tissue stored in a biobank or biorepository.\n   3. Efforts will be made to provide fresh frozen tissue in at least one quarter of the participating subjects. The proportion of subjects that might provide fresh frozen tissue might change based on the results from the molecular analysis.\n   4. Since some of the tests are performed in FFPE tissue, subjects providing fresh frozen tissue from a recent biopsy will have part of the sample processed in FFPE as per Laboratory manual.\n6. Subjects must have adequate haematological, renal, and hepatic function.\n7. For subjects requiring a tumour biopsy: subjects must have adequate coagulation function.\n8. Subjects must be willing to participate in a clinical trial with a matched therapy according to the molecular profile of his\u002Fher tumour.\n\nExclusion Criteria:\n\n1. Subjects with leptomeningeal disease should be excluded from this clinical trial.\n2. Subjects with known unstable brain metastases should be excluded from this clinical trial. Exception: Subjects who have undergone surgery and\u002For radiotherapy and in which brain metastases remain stable or decrease in size for six months after having completed therapy.\n3. Subjects with spinal cord compression not definitively treated with surgery and\u002For radiation.\n4. Subjects with uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, LVEF \\\u003C 50%, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n5. Subjects with inability to swallow tablets or capsules.\n6. Subjects with known HIV, hepatitis B or hepatitis C infection.\n7. Subjects with known history of malabsorption.\n\nEligibilty Criteria (PART B - iBASKET)\n\nInclusion Criteria:\n\n1. Subjects must have metastatic or unresectable malignant tumour, histologically or cytological confirmed and progressing to current therapy. Tumours must be refractory to standard therapy or for which standard therapy does not exist, or subjects may be unable to receive standard therapy.\n2. Patient must have ECOG performance status of 0 or 1.\n3. Subjects must be 18-year-old or older.\n4. Subjects must have measurable disease according to RECIST 1.1.\n5. Subjects must be willing to participate in a clinical trial with a matched therapy according to the molecular profile of his\u002Fher tumour.\n6. Tumours must harbour the following alterations.\n7. Subjects must have adequate hematological, renal, and hepatic function.\n8. For subjects requiring a tumour biopsy: subjects must have adequate coagulation function.\n9. A woman of childbearing potential must have a negative serum pregnancy test within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy test during the study.\n10. A woman must be either of the following:\n\n    1. Not of childbearing potential.\n    2. Of childbearing potential and practicing true abstinence during the entire period of the study, including up to 6 months after the last dose of study treatment is given.\n    3. Of childbearing potential and practicing 2 methods of contraception, including 1 highly effective user independent method and a second method. Participant must agree to continue contraception throughout the study and through 6 months after the last dose of study treatment.\n11. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment.\n12. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment.\n13. Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n1. Pregnant or breastfeeding women. Females of childbearing potential must have a negative serum pregnancy test within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy test during the study.\n2. Any approved anticancer therapy, including chemotherapy, hormonal therapy or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:\n\n   1. Hormone-replacement therapy or oral contraceptives.\n   2. Somatostatin analogues for the treatment of symptoms related with neuroendocrine tumours.\n   3. Gonadotropin-releasing hormone agonists or antiandrogens for prostate cancer.\n   4. Palliative radiotherapy for bone metastases \\> 2 weeks prior to Cycle 1, Day 1.\n3. Treatment with an investigational agent within 3 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer).\n4. Patients with recent major surgery or invasive procedure within 15 days before the fist dose of the study drug.\n5. Participant has unstable symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study.\n\n   a. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before enrolment are eligible, provided they have been either off corticosteroid treatment or are stable or tapering doses below 4 mg of dexamethasone.\n6. Patients with meningeal or leptomeningeal carcinomatosis.\n7. Uncontrolled intercurrent illness including, but not limited to, active infection, cardiovascular disease, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n8. Positive hepatitis B (hepatitis B virus \\[HBV\\]) surface antigen (HBsAg). Note: Subjects with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at Screening 1) a negative HBsAg and 2) an HBV DNA (viral load) below the lower limit of quantification, per local testing.\n9. Positive hepatitis C antibody (anti-HCV). Note: Subjects with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.\n10. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class III or greater), myocardial infarction within 3 months prior to Cycle 1, Day 1, unstable angina or unstable clinically meaningful arrhythmias.\n11. Another primary malignancy other than disease under study within 2 years prior to Cycle 1 Day 1, unless consider at low risk of relapse at Investigator discretion.\n12. Contraindications included in the product information of the drugs used in the study.\n\nOther protocol specified criteria for each module. The study center will determine if criteria for participation are met.",{"count":227,"type":21},1000,[24],"The global objective of this Basket of Basket study is to evaluate the antitumor activity of each matched therapies that will be evaluated through the study in small molecularly selected populations.\n\nThe objective of module 1 wil be to determine the overall response rate (ORR) at 12 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of atezolizumab in each of the arms of the module. All patients in genomically selected populations will receive atezolizumab 1200 mg IV every 3 weeks.\n\nThe objective of module 2 wil be to determine the overall response rate (ORR) at 16 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of futibatinib in each of the arms of the module. All patients in genomically selected populations will receive will receive futibatinib, 20 mg, once daily (QD) in 28-day cycles.\n\nThe objective of module 3 wil be to determine the overall response rate (ORR) at 12 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of amivantamab in each of the arms of the module. All patients in genomically selected populations will receive amivantamab 1050 mg intravenously (IV) for body weight \\\u003C 80 kg and 1400 mg for body weight \\>= 80 kg mg once weekly in Cycle 1 (with a split dose on Days 1-2) and then every 2 weeks in subsequent cycles (28-day cycles).",[231],"Advanced Solid Tumor",[231,233,234,235],"Cancer","Atezolizumab","Immunotherapy","2024-04-24",{"date":238,"type":36},"2024-04-25",{"date":240,"type":36},"2018-12-10",{"date":242,"type":21},"2026-11",{"name":42,"class":43},8,{"id":246,"slug":247,"hasResults":11,"nctId":248,"briefTitle":249,"officialTitle":250,"acronym":251,"eligibilityCriteria":252,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":253,"targetDuration":4,"studyType":255,"phases":4,"briefSummary":256,"conditions":257,"keywords":259,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":272,"lastUpdatePostDateStruct":273,"startDateStruct":275,"completionDateStruct":277,"leadSponsor":279,"locationsCount":44},"100509694","predictive-biomarkers-of-response-to-checkpoint-inhibitors-in-triple-negative-breast-cancer-a-multiomics-platform-100509694","NCT05916755","Predictive Biomarkers of Response to Checkpoint Inhibitors in Triple Negative Breast Cancer: a Multiomics Platform","Identification of Predictive Biomarkers of Response to Chemotherapy and Immune Checkpoint Inhibitors in Early Triple Negative Breast Cancer: an Integrative Multiomics Platform","PORTRAIT","Inclusion Criteria:\n\n* Histologically documented TNBC (negative human epidermal growth factor receptor 2 \\[HER2\\], estrogen receptor \\[ER\\], and progesterone receptor \\[PgR\\] status)\n* Stage 2 - 3 defined by the American Joint Committee of Cancer (AJCC) staging criteria 8th edition for breast cancer as assessed by the investigator based on radiological and\u002For clinical assessment\n* Patient is a candidate to receive NACT with or without ICI as assessed by the investigator\n* Patient is ≥ 18 years old at the time of consent to participate in this trial\n\nExclusion Criteria:\n\n* Metastatic disease on imaging (stage 4)",{"count":254,"type":21},100,"OBSERVATIONAL","Patients with stage II-III Triple negative breast cancer (TNBC) candidates to receive neoadjuvant chemotherapy (NACT) +\u002F- immune checkpoint inhibitor (ICI) will be included. Several samples from different tissues will be analyzed through different omics to establish predictive biomarkers of response to the treatment. Multiple algorithms will then be used to look for an integrative predictive algorithm that incorporates multi-parameter inputs in order to develop a clinical tool to assist clinicians in the process of treatment decision-making in TNBC.",[258],"Triple Negative Breast Cancer",[260,261,262,263,264,265,266,267,268,269,270,271],"Circulating biomarkers","clinical tool","immune checkpoint inhibitors","integrative algorithm","microbiome","multiomics","neoadjuvant chemotherapy","predictive biomarkers","radiomics","RNA-Sequencing","triple negative breast cancer","WGS","2023-06-20",{"date":274,"type":36},"2023-06-23",{"date":276,"type":36},"2023-01-13",{"date":278,"type":21},"2029-12",{"name":42,"class":43},""]