[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"advanced-melanoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:advanced-melanoma":29},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,27,0,25,[9,45,74,115,137,193,216,239,267,296,317,342,376,395,416,475,499,522,558,580,604,634,666,688,709],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":30,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100539045","high-intensity-exercise-and-high-fiber-diet-for-immunotherapy-outcomes-in-melanoma-patients-the-duo-trial-100539045",false,"NCT06298734","High-Intensity Exercise and High-Fiber Diet for Immunotherapy Outcomes in Melanoma Patients: The DUO Trial","Modulating Immune-Microbiome Axis Through High-Intensity Exercise and High-Fiber Diet for Immunotherapy Outcomes in Melanoma Patients: The DUO Trial","Inclusion Criteria:\n\n* Age ≥18 years.\n* Histologically diagnosed with melanoma.\n* Having been or newly receiving immunotherapy for at least one month.\n* Having a plan to continue immunotherapy for at least 8 weeks at the time of recruitment.\n* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2, indicating the ability to fulfill physical fitness and function assessments.\n* Ability to understand and willingness to provide informed consent.\n\nExclusion Criteria:\n\n* Participating in ≥ 150 minutes of moderate-to-vigorous aerobic exercise per week over the past month.\n* Consuming ≥ 30 grams\u002Fday of dietary fiber over the past month.\n* Having chronic medical conditions that are clinically unstable or uncontrolled with medications, deemed high-risk for exercise. These include but are not limited to unstable cardiac diseases, uncontrolled diabetes, and bone metastases with imminent risk of fracture.\n* Having a high risk for noncompliance with study procedures. This will be determined by the study team based on the history of missed oncology appointments (i.e., ≥3 no-shows in 6 months) and poor responsiveness during recruitment (i.e., ≥3 unreturned contacts).\n* Patients who are non-English speaking and cannot complete the participant surveys.","ALL","18 Years",{"count":20,"type":21},40,"ESTIMATED","INTERVENTIONAL",[24],"NA","The purpose of this study is to determine whether high-intensity exercise and high-fiber diet are feasible and improve various health outcomes among participants with advanced melanoma receiving immunotherapy.\n\nThe names of the groups in this research study are:\n\n* High-Intensity Exercise (EX)\n* High-fiber Diet (DT)\n* Combined High-Intensity Exercise and High-Fiber Diet (COMB)\n* Attention Control (AC)",[27,28,29],"Melanoma (Skin)","Skin Cancer","Advanced Melanoma",[31,28,29],"Melanoma","RECRUITING","2026-06-15",{"date":35,"type":36},"2026-06-17","ACTUAL",{"date":38,"type":36},"2024-07-01",{"date":40,"type":21},"2027-03-31",{"name":42,"class":43},"Fred Hutchinson Cancer Center","OTHER",2,{"id":46,"slug":47,"hasResults":12,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":51,"eligibilityCriteria":52,"healthyVolunteers":53,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":54,"targetDuration":4,"studyType":22,"phases":56,"briefSummary":58,"conditions":59,"keywords":61,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":64,"lastUpdatePostDateStruct":65,"startDateStruct":67,"completionDateStruct":69,"leadSponsor":71,"locationsCount":73},"100595056","phase-1-ab821-in-adult-participants-with-locally-advanced-or-metastatic-solid-tumors-100595056","NCT07027488","AB821 in Adult Participants With Locally Advanced or Metastatic Solid Tumors","An Open-Label, Phase 1 Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AB821 in Adult Participants With Locally Advanced or Metastatic Melanoma and Other Solid Tumors","Asher-BioAB821","Inclusion Criteria:\n\n1. ≥18 years at the time consent is signed.\n2. Ability to provide written informed consent for the study.\n3. ECOG PS of 0 or 1.\n4. Participants of childbearing potential must not be pregnant at enrollment and agree to comply with contraception requirements. Participants with partners of childbearing potential must also comply with contraception requirements.\n5. Adequate organ function as defined below. Specimens must be collected within seven days prior to the start of the study treatment (i.e., Cycle 1 Day 1 \\[C1D1\\]) including:\n\n   ANC\\> 1500\u002Ful Platelet count\\>100,000 Hb\\>9 g\u002Fdl Calculated creatinine clearance\\> 50 mL\u002Fmin Total bilirubin greater than or equal to 1.5 x ULN or direct bilirubin greater than or equal to ULN for participants with total bilirubin \\> 1.5 x ULN PT INR \\> 1.5 x ULN unless on anticoagulation Albumin \\> 3g\u002Fdl\n6. Life expectancy of ≥12 weeks, per treating investigator's judgment.\n7. For Melanoma participants: Participants with unresectable or metastatic melanoma that have progressed on or after PD-1\u002FPD-L1 checkpoint blockade (alone or with either CTLA-4 or LAG-3 checkpoint blockade).\n8. For other tumor types: Must have a recurrent histologically or cytologically proven metastatic or locally advanced solid tumor (non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), Merkel-cell carcinoma, bladder cancer, or squamous cell carcinoma of the head and neck (SCCHN)), meeting each of the following:\n\n   1. Tumor that is not amenable to curative treatment with surgery or radiation.\n   2. Tumor for which immune checkpoint inhibitors form part of standard-of-care therapy.\n   3. Participant has received at least one prior line of systemic anticancer therapy in the recurrent or metastatic setting.\n9. Has measurable disease per RECIST v1.1 as assessed by the local site investigator\u002Fradiology.\n\nExclusion Criteria:\n\n1. Has a diagnosis of immunodeficiency.\n2. Prior stem cell, bone marrow, or organ transplant.\n3. Known history of HIV infection. No HIV testing is required unless mandated by local health authority.\n4. History of HBV (defined as HBV surface antigen reactive) or active HCV.\n5. Active autoimmune disease (non-immunotherapy induced conditions) that has required systemic treatment in the past two years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic immune-suppressive treatment and is allowed.\n6. Active Grade ≥2 diarrhea or enterocolitis.\n7. Known active CNS metastases and\u002For carcinomatous meningitis. Individuals with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression for at least two weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment).\n8. Any other current or previous malignancy within the previous three years except neoplasms that, in the opinion of the treating investigator and with the agreement of the sponsor-investigator, will not interfere with study-specific endpoints, e.g. basal cell carcinoma, localized tumors that have been fully excised with curative intent and no evidence of recurrence or metastasis, prostate cancer that is asymptomatic and does not require therapy other than anti-androgen therapy.\n9. Participant is a regular user, as determined by treating investigator judgment (including recreational use), of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing the Informed Consent Form (ICF).\n10. Has clinically significant heart disease that affects normal activities, including, unstable angina, or history of congestive heart failure (New York Heart Association Class II IV).\n11. History of acute myocardial infarction within the last six months.\n12. Has a history of new or worsening thrombosis (DVT\u002FPE, other thrombo-embolic disease) within the last six months.\n13. Has a mean QTcF value of \\>470 ms.\n14. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the individuals' participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator.\n15. Has an active infection, requiring systemic therapy.\n16. Has had a severe hypersensitivity reaction to any components of the study treatment or any of their excipients.\n17. Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days prior the first dose of study treatment.\n18. Has received more than five prior lines of systemic treatment in the recurrent\u002Fmetastatic setting.\n19. Has received prior radiotherapy within two weeks of start of study treatment or has had a history of radiation pneumonitis.\n20. Has a history of grade 3-4 autoimmune myocarditis or a history of Guillain Barre Syndrome.\n21. History of congestive heart failure with an ejection fraction \\\u003C 40%.\n22. Participant with NSCLC only: Has received radiation therapy to the lung that is \\>30 Gy within six months of the first dose of study treatment.\n23. Has received previous IL-21 based therapy or prior therapy with AB248\n24. Prior systemic anticancer therapy including investigational agents within four weeks or, if shorter, within five half-lives prior to first dose of study treatment.\n25. Major surgery from which the participant has not fully recovered\n26. Has received a live or live attenuated vaccine within 30 days\n27. Current use of any prohibited concomitant medications.\n28. A participant of childbearing potential who has a positive serum pregnancy test within 14 days prior to treatment.",true,{"count":55,"type":21},50,[57],"PHASE1","This study is a first-in-human, open-label, nonrandomized, single center Phase 1 dose-escalation study to assess the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of AB821 monotherapy given every 2 weeks (Q2W) or every 3 weeks (Q3W) in participants with recurrent locally advanced or metastatic melanoma and other immune-responsive solid tumors. Immune-responsive solid tumors are defined as those for which immune checkpoint inhibitors form part of the standard-of-care therapy.",[60,29],"Advanced Melanoma and Normal or Impaired",[62,63],"AB821","immune-responsive solid tumors","2026-06-12",{"date":66,"type":36},"2026-06-16",{"date":68,"type":36},"2025-08-05",{"date":70,"type":21},"2027-08",{"name":72,"class":43},"Yale University",1,{"id":75,"slug":76,"hasResults":12,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":4,"eligibilityCriteria":80,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":81,"targetDuration":4,"studyType":22,"phases":83,"briefSummary":85,"conditions":86,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":107,"lastUpdatePostDateStruct":108,"startDateStruct":109,"completionDateStruct":111,"leadSponsor":113,"locationsCount":73},"100624088","phase-4-morning-versus-afternoon-administration-of-immunotherapy-for-the-treatment-of-advanced-or-metastatic-solid-tumors-the-knight-shift-study-100624088","NCT07405086","Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study","Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study","Inclusion Criteria:\n\n* Must provide written informed consent before any study-specific procedures or interventions are performed\n* Aged ≥ 18 years\n* Histologically confirmed advanced\u002Fmetastatic solid tumor as follows:\n\n  * Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \\[ICI\\]-eligible)\n  * Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),\n  * Renal cell carcinoma (RCC)\n  * Biliary-tract cancer (BTC)\n  * Hepatocellular carcinoma (HCC)\n  * Melanoma\n* Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\nExclusion Criteria:\n\n* Prior ICI-based regimen for treatment of cancer\n* Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg\u002Fday of prednisone (or equivalent corticosteroid)\n* Uncontrolled autoimmune disease requiring immunosuppression\n* Active, uncontrolled central nervous system (CNS) metastases",{"count":82,"type":21},160,[84],"PHASE4","This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.",[87,88,89,90,91,29,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106],"Advanced Biliary Tract Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Hepatocellular Carcinoma","Advanced Lung Non-Small Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Melanoma","Metastatic Renal Cell Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","2026-06-10",{"date":64,"type":36},{"date":110,"type":36},"2026-06-08",{"date":112,"type":21},"2028-12-31",{"name":114,"class":43},"OHSU Knight Cancer Institute",{"id":116,"slug":117,"hasResults":12,"nctId":118,"briefTitle":119,"officialTitle":120,"acronym":4,"eligibilityCriteria":121,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":122,"enrollmentInfo":123,"targetDuration":4,"studyType":22,"phases":125,"briefSummary":126,"conditions":127,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":129,"lastUpdatePostDateStruct":130,"startDateStruct":131,"completionDateStruct":133,"leadSponsor":135,"locationsCount":4},"100643829","phase-1-sitagliptin-with-pembro-in-rcc-and-melanoma-100643829","NCT07634380","Sitagliptin With Pembro in RCC and Melanoma","A Phase 1b Study of Sitagliptin in Combination With Pembrolizumab in Refractory or Relapsed Advanced Renal Cell Carcinoma and Melanoma","INCLUSION CRITERIA\n\n1. Histologically and\u002For cytologically confirmed unresectable metastatic renal cell carcinoma with clear cell component with no neuroendocrine differentiation component) or unresectable metastatic melanoma (excluding uveal or mucosal melanoma) that have progressed on treatment with an anti-PD-1\u002FPD-L1 mAb administered either as a monotherapy, or in combination with other immune checkpoint inhibitors or other therapies. Progression on treatment with an anti-PD-1\u002FPD-L1 mAb is defined by meeting all of the following criteria:\n\n   1. Has received at least 2 doses of an approved anti-PD-1\u002FPD-L1 mAb\n   2. Has demonstrated disease progression after anti-PD-1\u002FPD-L1 mAb as defined by RECIST v1.1. The initial evidence of disease progression (PD) is confirmed by a second assessment no less than 4 weeks from the date of the first documented PD\n   3. Progressive disease has been documented within 12 weeks from last dose of anti-PD-1\u002FPD-L1 mAb (refractory disease) or ≥12 weeks from last dose of anti-PD-1\u002FPD-L1 mAb (late relapse)\n2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2\n3. Measurable disease meeting the following criteria:\n\n   1. At least 1 lesion of ≥10mm in the longest diameter for a non-lymph node or ≥15mm in the short-axis diameter for a lymph node that is serially measurable according to RECIST v1.1 using computerized tomography\u002Fmagnetic resonance imaging (CT\u002FMRI)\n   2. Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show subsequent evidence of substantial size increase to be deemed a target lesion\n4. Aged 18 years and older\n5. The participant is capable of understanding and complying with the protocol requirements and has signed the informed consent document\n6. Participants must have recovered adequately from any toxicity and\u002For complications from major surgery prior to starting therapy to \\\u003C Grade 1 CTCAE unless clinically insignificant and\u002For stable on supportive therapy.\n7. No active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with the use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment\n8. Women of childbearing potential (WOCBP) - defined as females who have experienced menarche, have not undergone permanent surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), and are not postmenopausal (no menses for ≥12 consecutive months without an alternative medical cause) - must meet all of the following criteria:\n\n   1. Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.\n\n      • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test must be performed and must be negative prior to enrollment.\n   2. Agree to use at least one highly effective method of contraception during the study and for a minimum of 4 months after the last dose of pembrolizumab.\n\n   Acceptable highly effective methods include:\n   * Combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, or transdermal)\n   * Progestogen-only hormonal contraception (oral, injectable, or implantable)\n   * Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)\n   * Bilateral tubal occlusion\n   * Vasectomized partner (if confirmed as the sole sexual partner)\n   * Complete sexual abstinence (only if this is the participant's usual and preferred lifestyle)\n9. Male participants must:\n\n   * Use a condom with spermicide during the study and for at least 4 months after the last dose of pembrolizumab, and\n   * Ensure that their female partners of childbearing potential use an additional highly effective method of contraception during this period.\n10. Able to swallow pills\n11. Adequate archival tissue sample ( 5-10 slides at 5µm) of at least one tumor lesion is mandatory. If archival tissue is not available, Participant must agree to a new biopsy sample.\n\nEXCLUSION CRITERIA\n\nA patient meeting any of the following criteria is not eligible to participate in this study:\n\n1. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n2. Participants with renal cell carcinoma with histologic\u002Fcytologic component of neuroendocrine differentiation\n3. Participants with uveal or mucosal melanoma\n4. Participants with both renal cell carcinoma and melanoma\n5. Participants with diabetes mellitus requiring insulin therapy or sulfonylurea\n6. Participants taking oral antihyperglycemics (e.g., metformin, DPP-4 inhibitor, SGLT-2 inhibitor) for any cause within 3 months of starting study drug\n7. Participants with documented history of hypoglycemia requiring medical intervention, oral or intravenous carbohydrate ( glucose, dextrose, fruit juice, or any form of glucagon) or who in the opinion of the investigator are not suitable to receive sitagliptin\n8. Taking digoxin within 6 months of starting study drug\n9. Known intolerance or history of severe hypersensitivity reaction (such as anaphylactic shock or angioedema) to sitagliptin or monoclonal antibody\n10. Prior anticancer treatment within 28 days (or 5 times the half-life, whichever is shorter) or any investigational agent within 30 days prior to the first dose of study treatment.\n11. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of sitagliptin\n12. Active uncontrolled infection requiring systemic therapy.\n13. Participant is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C\n14. History of organ allograft (participant has had an allogenic tissue\u002Fsolid organ transplant)\n15. Biologic response modifiers (e.g., granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before the first dose of study treatment\n16. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical study\n17. Females who are pregnant or breastfeeding\n18. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 7.5mg\u002Fd of prednisone or equivalent) may be approved after consultation with the sponsor\n19. Has history of (non-infectious) pneumonitis that required steroids, or current pneumonitis\n20. Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted","99 Years",{"count":124,"type":21},64,[57],"This study is testing whether adding the drug sitagliptin to the standard immunotherapy pembrolizumab is safe and may help people with advanced melanoma or advanced renal cell carcinoma (kidney cancer) whose cancer has stopped responding to prior PD-1 or PD-L1 immunotherapy.\n\nThe study has two parts. In the first part, small groups of participants will receive different doses of sitagliptin along with a fixed dose of pembrolizumab. This helps researchers find the highest dose of sitagliptin that can be given safely. In the second part, more participants will receive the safest dose to see how well the drug combination works against their cancer.",[92,29],"NOT_YET_RECRUITING","2026-06-03",{"date":110,"type":36},{"date":132,"type":21},"2026-05-15",{"date":134,"type":21},"2031-04-10",{"name":136,"class":43},"Fernando Maciel Barbosa",{"id":138,"slug":139,"hasResults":12,"nctId":140,"briefTitle":141,"officialTitle":142,"acronym":4,"eligibilityCriteria":143,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":144,"targetDuration":4,"studyType":22,"phases":146,"briefSummary":147,"conditions":148,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":184,"lastUpdatePostDateStruct":185,"startDateStruct":187,"completionDateStruct":189,"leadSponsor":191,"locationsCount":73},"100442316","phase-1-iacs-6274-with-or-without-bevacizumab-and-paclitaxel-for-the-treatment-of-advanced-solid-tumors-100442316","NCT05039801","IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors","A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-Tumor Activity of IACS-6274 as Monotherapy and in Combination in Patients With Advanced Solid Tumors","Inclusion Criteria All Parts\n\n1. Provision of written informed consent prior to any study related procedures and compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n2. Male or female patients ≥18 years of age at the time of study entry who agree to participate by giving written informed consent prior to participation in any study related activities.\n3. Histologically or cytologically confirmed advanced solid tumors, specifically:\n\n   Dose Escalation for Part A may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2\u002FSTK11\u002FNF1 mutations Patients with low ASNS expression levels (HGSOC or endometrial cancer) Patients who had immunotherapy (IO) melanoma (Minimum treatment duration of prior PD-1 or PD-L1-containing regimen of 12 weeks \\[or equivalent of 2 response evaluations\\]).\n\n   Patients with post-platinum HNSCC Patients with chondrosarcoma Patients with ARID1A mutant clear cell ovarian cancer\n\n   Dose Escalation for Part B may include:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer that is platinum-resistant, defined as disease relapse within a platinum-free interval (PFI, or the time elapsed from the last date of platinum dose until PD) of \\\u003C 6 months, and with less than 5 prior therapies\n\n   Dose Expansion for Part B limited to:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer with low ASNS expression levels that is platinum-resistant, defined as disease relapse within a PFI of \\\u003C 6 months, and with less than 5 prior therapies.\n\n   Dose Escalation for Part C may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2 mutations Patients with tumors harboring PIK3CA hotspot mutations, activating AKT mutations, and inactivating PTEN mutations (irrespective of KEAP1\u002FNFE2L2 mutations) Patients with low ASNS expression levels (HGSOC)\n\n   Dose Expansion for Part C limited to:\n\n   Patients with NSCLC with actionable KEAP1\u002FNFE2L2 mutations Patients with HGSOClow ASNS expression levels (irrespective of biomarker status for KEAP1\u002FNFE2L2)\n4. Patients must have received at least one line of therapy for advanced stage disease and be refractory or ineligible to available existing therapy(ies) known to provide clinical benefit for their condition.\n5. Prior treatment with chemotherapy, radiotherapy, immunotherapy or any investigational therapies must have been completed at least 3 weeks or at least five half lives, whichever is shorter, before the study drug administration, and all AEs (excluding alopecia and peripheral neuropathy) have either returned to ≤Grade 1 or stabilized. Patients with concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) are allowed.\n6. Fresh and\u002For archival tumor tissue from a biopsy obtained between the completion of the most recent line of treatment until study entry must be available for mutation and biomarker analysis. If available, archival tumor tissue from the time of initial diagnosis or the most recent biopsy (archival and\u002For fresh) will be collected. For ovarian cancer patients, a fresh biopsy must be collected in addition to archival tumor tissue. NOTE: No fresh tumor tissue will be required if a previous biopsy detected the selected mutations for each cohort. In all cases, procedures to obtain fresh tumor tissue should not put the patient at undue risk, and should only be performed if the risk is minimal (no greater than 2% risk of serious or severe complications).\n7. Patients must have at least 1 lesion (measurable and\u002For non-measurable) that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessments.\n8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.\n9. Adequate organ function as indicated by the following laboratory values:\n\n   Absolute neutrophil count (ANC) ≥1.0×109\u002FL Platelets ≥100×109\u002FL Hemoglobin ≥9.0 g\u002FdL (\\>5.59 mmol\u002FL) Creatinine clearance (CrCl) \\>50 mL\u002Fmin. Actual body weight should be used for calculating creatinine clearance using the Cockroft Gault equation (except for patients with body mass index \\>30 kg\u002Fm2 when the lean body weight should be used, and without the need for chronic dialysis therapy).\n\n   Serum total bilirubin ≤1.5×ULN (with the exception of patients with known thalassemia minor mutations or Gilbert's syndrome: serum total bilirubin must be \\\u003C3×ULN in these patients) Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN for patients with liver metastases)\n10. Adequate cardiac function with a left ventricular ejection fraction ≥50%\n11. Female patients of non childbearing potential, who are physiologically incapable of becoming pregnant, are eligible to enter and participate in the study if they:\n\n    have had a hysterectomy, OR have had a bilateral oophorectomy, OR have had a bilateral salpingectomy, OR is postmenopausal (total cessation of menses for ≥2 years, or follicle stimulating hormone ≥50 IU\u002FL).\n12. Female patients of childbearing potential, who are not post-menopausal or surgically sterile and intent to be sexually active with a non-sterile male partner, are required to use one form of highly effective contraception combined with a barrier method (male condom, female condom, cervical cap, diaphragm with spermicide, or contraceptive sponge with spermicide) of contraception starting before entering the study and until 4 weeks after the last dose of treatment.\n\n    Highly effective non-hormonal contraceptive methods that are acceptable include:\n\n    Total\u002Ftrue abstinence\\*\\*\\* for the total duration of the study treatment and for at least 1 month after the last dose of study treatment. Periodic abstinence using methods such as calendar ovulation, symptothermal, post ovulation methods, declaration of abstinence solely for the duration of a trial, or withdrawal are not acceptable methods of contraception.\n\n    Having a vasectomized sexual partner, who received post-vasectomy confirmation of azoospermia, combined with a barrier method as described above.\n\n    Bilateral tubal occlusion combined with a barrier method as described above. Intrauterine device with copper banded coils, combined with a barrier method as described above.\n\n    Highly effective hormonal contraceptive methods that are acceptable include:\n\n    Combined oral pill contraception (normal and low-dose oral pills, or progesterone-based oral pills using desogestrel) combined with a barrier method as described above. NOTE: cerazette is currently the only highly efficacious progesterone-based pill available.\n\n    Injection (e.g., medroxyprogesterone) combined with a barrier method as described above.\n\n    Patch (e.g., norelgestromin or ethinyl estradiol transdermal system) combined with a barrier method as described above.\n\n    Implants (etonorgestrel-releasing) combined with a barrier method as described above.\n\n    Intravaginal device (e.g., ethinyl estradiol- or etonogestrel-releasing) combined with a barrier method as described above.\n\n    Intrauterine system (levonorgestrel-releasing) combined with a barrier method as described above.\n\n    In addition to the to use one form of highly effective contraception combined with a barrier method, female patients of childbearing potential must have a negative serum pregnancy test at screening (within 7 days of the start of treatment) and must not be breastfeeding.\n13. Non-sterile men, who are not sexually abstinent and intend to be sexually active with a woman of childbearing potential, must use a condom from the start of the trial and until 16 weeks after the last dose of treatment, or must practice total abstinence\\*\\*\\* for the total duration of the study treatment and at least 3 months after the last dose of study treatment. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female partners of childbearing potential should consider the use of at least one contraception method describe above. If the female partner is pregnant, male participants should use a condom plus spermicide.\n\n    * Total\u002Ftrue abstinence is defined as a patient who refrains from any form of sexual intercourse, and this is in line with their usual and\u002For preferred lifestyle.\n\nExclusion Criteria All Parts\n\n1. Prior malignancy within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast or bladder.\n2. Known primary central malignancy or symptomatic central nervous system metastasis(es).\n\n   Note: Patients with stable, previously treated brain metastases may participate if neurologic symptoms have resolved, patients have been off steroids (at least 7 days for Part A and Part B, and at least 4 weeks for Part C), and there is no evidence of disease progression by imaging for at least 2 weeks before the first dose of study treatment.\n3. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following cardiac conditions:\n\n   1. Any unstable cardiac arrhythmia within 6 months prior to enrolment\n   2. Prolongation of the Fridericia corrected QT (QTcF) interval defined as \\>450 ms for males and \\>470 ms for females\n   3. History of any of the following cardiovascular conditions within 6 months of enrolment:\n\n      * cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association.\n4. Major surgical intervention within 28 days before study drug administration, or an anticipated need for major surgery during the study.\n5. Significant acute or chronic infections.\n6. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.\n7. Treatment with strong cytochrome P450 subtype 3A4 (CYP3A4) inducers and inhibitors (including grapefruit juice) within 2 weeks of the first dose of study drug NOTE: patients must have stopped taking St. John's Wort 3 weeks prior to the start of treatment and stopped taking enzalutamide 4 weeks prior to the start of treatment.\n8. Treatment with strong CYP450 subtype 2D6 (CYP2D6) inhibitors or sensitive CYP3A4 substrates within 7 days of the first dose of study drug.\n9. Radiotherapy within 4 weeks prior to the start of study drug. Palliative radiotherapy for symptomatic control is acceptable if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned.\n10. Underlying medical conditions (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases), for which in the investigator's opinion will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or AEs.\n11. History of allergic reactions attributed to compounds of similar chemical or biological composition to any of the compounds in the study.\n12. Known history of alcohol or drug abuse.\n13. Legal incapacity or limited legal capacity.\n14. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation. Patients should not have gastrointestinal illnesses (such as refractory nausea and vomiting, chronic gastrointestinal disease or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretionof IACS-6274 and capivasertib, which are oral agents.\n15. Patients unwilling to comply with protocol requirements related to the assigned part.\n16. Any other disease, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.\n\nPart B Specific Exclusion Criteria (B1) Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, three or more features of partially controlled asthma).\n\n(B2) Patient has a known hypersensitivity to paclitaxel or bevacizumab components or excipients.\n\n(B3) Patient has a history of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.\n\n(B4) Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate \\\u003C2 g of protein in 24 hours to be eligible).\n\n(B5) Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).\n\n(B6) Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. (B7) Patient has pre-existing peripheral neuropathy that is Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.\n\n(B8) Patient requires paracentesis 2 weeks prior to trial enrolment. Part C Specific Exclusion Criteria (C1) History of another primary malignancy, except for a malignancy treated with curative intent, with no known active disease ≥5 years before the first dose of treatment, with low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy.\n\n(C2) Patient has a known hypersensitivity to capivasertib components or any excipients of the product.\n\n(C3) Clinically significant abnormalities of glucose metabolism as defined by any of the following: Diagnosis of diabetes mellitus type I or II (irrespective of management), Glycosylated haemoglobin (HbA1c) \\>8% (64 mmol\u002Fmol) (C4) Patients with evidence of severe or uncontrolled systemic liver disease including severe hepatic impairment, or abnormal liver enzymes at screening (AST or ALT \\>2.5 x ULN; total bilirubin \\>1.5 x ULN).\n\n(C5) Patients with elevated alkaline phosphatase (ALP) can be enrolled if the abnormal value is due to the presence of bone metastasis, but liver function is considered adequate according to the principal investigator.\n\n(C6) Patients with persistent toxicities (Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included after consultation with the sponsor and the study physician.\n\n(C7) Patients with spinal cord compression or leptomeningeal disease not requiring steroids for at least 4 weeks prior to start of study intervention.\n\n(C8) Patients with clinically significant cardiovascular disease including, but not limited to, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. In addition, patients will be excluded based on the study physician's judgment of the following criteria:\n\n* Mean resting corrected QT interval \\>470ms, obtained from triplicate ECGs performed at screening.\n* Medical history significant for arrhythmia that is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation regardless of treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be included based on the study physician's judgment.\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia of Grade ≥1, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relative, history of QT prolongation associated with other medications that required discontinuation of the medication.\n* Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association Grade ≥2.\n* Uncontrolled hypotension: SBP \\\u003C90 mmHg and\u002For DBP \\\u003C50 mmHg.\n* Cardiac ejection fraction outside institutional range of normal or \\\u003C50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \\[MUGA\\] scan if an echocardiogram cannot be performed or is inconclusive).\n\n(C9) Patients with active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice) are excluded.\n\n(C10) Patients with active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening are excluded.\n\nHuman immunodeficiency virus (HIV) positive patients with a viral load \\> 400 copies\u002FmL and a CD4+ T-cell count of \\\u003C350 cells\u002FuL or with a history of an acquired immunodeficiency syndrome (AIDS) opportunistic infection within the past 12 months are excluded. Patients with a higher viral load or lower CD4+ count (\\\u003C 350 cells\u002FuL) may be considered for eligibility if the patient has a potentially curable malignancy or for interventions in a later stage of development that have demonstrated prior activity with a given cancer.\n\nHIV-positive patients receiving antiretroviral therapies should be on established ART for at least four weeks before starting treatment to ensure that treatment is tolerated and that toxicities are not confused with investigational drug toxicities. HIV-positive patients receiving antiretroviral therapies that are strong CYP3A4\u002F5 inhibitors\u002F inducers or sensitive substrates of CYP3A4 will be excluded due to the potential for drug-drug interaction with capivasertib.\n\n(C12) Patients who are undergoing any concurrent anticancer treatment or any concomitant medication that may interfere with the study drugs according to local clinical guidelines are excluded.\n\n(C13) Patients who received palliative radiotherapy within 2 weeks prior to the start of study treatment; or radiotherapy to more than 30% of the bone marrow within 4 weeks before the start of study treatment are excluded.",{"count":145,"type":21},54,[57],"To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.",[149,88,91,29,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183],"Advanced Endometrial Carcinoma","Advanced Ovarian Clear Cell Adenocarcinoma","Chondrosarcoma","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Pathologic Stage III Cutaneous Melanoma AJCC v8","Pathologic Stage IIIA Cutaneous Melanoma AJCC v8","Pathologic Stage IIIB Cutaneous Melanoma AJCC v8","Pathologic Stage IIIC Cutaneous Melanoma AJCC v8","Pathologic Stage IIID Cutaneous Melanoma AJCC v8","Pathologic Stage IV Cutaneous Melanoma AJCC v8","Recurrent Ovarian High Grade Serous Adenocarcinoma","Refractory Endometrial Carcinoma","Refractory Head and Neck Squamous Cell Carcinoma","Refractory Melanoma","Refractory Ovarian Clear Cell Adenocarcinoma","Refractory Ovarian High Grade Serous Adenocarcinoma","Stage III Ovarian Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Ovarian Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","2026-05-29",{"date":186,"type":36},"2026-06-01",{"date":188,"type":36},"2021-09-30",{"date":190,"type":21},"2028-06-30",{"name":192,"class":43},"M.D. Anderson Cancer Center",{"id":194,"slug":195,"hasResults":12,"nctId":196,"briefTitle":197,"officialTitle":198,"acronym":4,"eligibilityCriteria":199,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":200,"targetDuration":4,"studyType":22,"phases":202,"briefSummary":204,"conditions":205,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":132,"lastUpdatePostDateStruct":206,"startDateStruct":208,"completionDateStruct":210,"leadSponsor":212,"locationsCount":215},"100600587","phase-1-a-trial-of-lbl-024-monotherapy-lbl-024-combined-with-lbl-007-or-toripalimab-in-patients-with-advanced-melanoma-100600587","NCT07099430","A Trial of LBL-024 Monotherapy, LBL-024 Combined With LBL-007 or Toripalimab in Patients With Advanced Melanoma","An Open-label, Multicenter Phase Ib\u002FII Clinical Study to Evaluate the Efficacy and Safety of LBL-024 Monotherapy, LBL-024 in Combination With LBL-007 or Toripalimab in Patients With Advanced Melanoma","Inclusion Criteria:\n\n1. Agree to follow the trial treatment regimen, visit schedule,laboratory test, and comply with other requirements of the protocol, and voluntarily enroll in the study and sign the written informed consent.\n2. At the time of signing the informed consent form, the age was ≥ 18 years old, and the gender was not limited.\n3. The Eastern Cooperative Oncology Group's physical status scoring standard (ECOG) is 0\\~1.\n4. The expected survival time is at least 12 weeks.\n5. According to the evaluation of RECIST 1.1 （Response Evaluation Criteria in Solid Tumours）, the subjects enrolled have at least one measurable neoplasm lesion.\n6. Male of childbearing potential and Females of childbearing age are willing to take highly effective contraceptive measures From the signing of the informed consent form to within 6 months after the last administration of the trial drug.\n\nExclusion Criteria:\n\n1. Subjects who received live vaccination within 4 weeks before the first dose or were planned to receive live vaccination during the study period and 4 weeks after the dose.\n2. Major surgery or other treatment or diagnosis that has a significant impact on the subject within 4 weeks before the first dose.\n3. Patients with active, or who have had and have the possibility of recurrence of autoimmune diseases.\n4. History of severe cardiovascular and cerebrovascular disorder.\n5. Active infectious disease.\n6. History of mental illness (interfering with understanding or giving informed consent), drug abuse, alcoholism, or drug addiction.\n7. Women during pregnancy or lactation.\n8. The investigator believes that the subject has other conditions that may affect compliance or are not suitable for participating in this study.",{"count":201,"type":21},200,[57,203],"PHASE2","This study is an open-label, multicenter phase Ib\u002FII study to evaluate the efficacy and safety of LBL-024 monotherapy, LBL-024 in combination with LBL-007 or toripalimab in patients with advanced melanoma,To evaluate the preliminary efficacy and safety of LBL-024 monotherapy and combination therapy in patients with advanced melanoma.",[29],{"date":207,"type":36},"2026-05-18",{"date":209,"type":36},"2025-09-05",{"date":211,"type":21},"2027-12-30",{"name":213,"class":214},"Nanjing Leads Biolabs Co.,Ltd","INDUSTRY",15,{"id":217,"slug":218,"hasResults":12,"nctId":219,"briefTitle":220,"officialTitle":221,"acronym":4,"eligibilityCriteria":222,"healthyVolunteers":12,"sex":17,"minAge":223,"maxAge":4,"enrollmentInfo":224,"targetDuration":4,"studyType":22,"phases":226,"briefSummary":228,"conditions":229,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":230,"lastUpdatePostDateStruct":231,"startDateStruct":232,"completionDateStruct":234,"leadSponsor":236,"locationsCount":238},"100536388","phase-3-vo-and-nivolumab-vs-physicians-choice-in-advanced-melanoma-that-progressed-on-anti-pd-1--anti-ctla-4-drugs-ignyte-3-100536388","NCT06264180","VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs [IGNYTE-3]","Randomized, Ph3 Clinical Study Comparing Vusolimogene Oderparepvec in Combination With Nivolumab Vs Treatment of Physician's Choice in Patients With Advanced Melanoma That Progressed on Anti-PD-1 and Anti-CTLA-4 Containing Treatment [IGNYTE-3]","Key Inclusion Criteria:\n\nI 1. Male or female who is 12 years of age or older at the time of signed informed consent.\n\nI 2. Patients with histologically or cytologically confirmed unresectable or metastatic Stage IIIb through IV\u002FM1a through M1d cutaneous melanoma, as per AJCC staging system, 8th edition).\n\nI 3. Confirmed disease progression (PD) on an anti-PD-1 antibody treatment and an anti-CTLA-4 antibody treatment, administered as either a combination regimen (eg, nivolumab + ipilimumab) or in sequence.\n\n1. Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks (note: treatment with prior pembrolizumab therapy when administered every 6 weeks must have continued for a minimum of 12 weeks \\[ie, 2 treatment cycles\\]). Any number of doses of prior anti-CTLA-4 therapy may have been administered in combination with an anti-PD-1. The anti-PD-1-containing therapy must be the immediate prior line of treatment before randomization (for patients with BRAF mutation, see I 4).\n2. Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody (eg, due to documented clinically significant comorbidities or history of immune-related adverse events) are eligible for the study if they have confirmed PD on an anti-PD-1 antibody (including unresectable disease relapse during adjuvant therapy or \\\u003C 6 months from completion of adjuvant therapy).\n3. Disease progression must have been confirmed and documented using clinical or radiological assessment by 2 assessments at least 4 weeks apart while being treated with an anti-PD-1 antibody and an anti-CTLA-4 antibody. Radiological confirmation of PD can occur during the Screening period for this study. Treatment with prior anti-PD-1 therapy must have continued from the time of initial tumor progression until confirmation of PD (ie, such that no doses of anti-PD-1 therapy were missed).\n\nNote: If radiographic progression at the initial scan where PD was documented is accompanied by clear clinical progression, defined as a decline in performance status directly attributed to disease or increased disease-related symptoms, anti-PD-1 therapy does not need to continue. For patients with documented PD while on adjuvant therapy with an anti-PD-1 therapy, a confirmatory biopsy can be used in place of a confirmatory scan.\n\nI 4. Has documented BRAF V600 mutation status or must consent to BRAF V600 mutation testing per local institutional standards during the Screening period. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to randomization, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity.\n\nNote: Prior exposure to BRAF-directed therapy (with or without a MEK inhibitor) includes treatment in the adjuvant setting. One line of BRAF-directed therapy (with or without a MEK inhibitor) can be the most recent systemic treatment administered before randomization.\n\nI 5. Has least 1 measurable tumor of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes) and injectable lesion(s) of at least 1 cm in longest diameter.\n\nI 6. Has adequate hematologic function, including:\n\n1. White blood cell (WBC) count ≥ 2.0 × 109\u002FL\n2. Absolute neutrophil count (ANC) ≥ 1.5 × 109\u002FL\n3. Platelet count ≥ 75 × 109\u002FL\n4. Hemoglobin ≥ 8 g\u002FdL (without packed red blood cell \\[RBC\\] transfusion within 2 weeks of dosing)\n\nI 7. Has adequate hepatic function, including:\n\n1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN; \\\u003C 2.0 × ULN for patients with known Gilbert syndrome or liver metastases)\n2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × ULN (or ≤ 5.0 × ULN, if liver metastases are present)\n3. Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases are present) I 8. Has adequate renal function, defined as serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 3 0 mL\u002Fminute\u002F1.73 m2 (measured using Chronic Kidney Disease Epidemiology Collaboration \\[CKD-EPI\\] formula).\n\nI 9. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \\[INR\\] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Note: Patients who are on chronic anticoagulant therapy may be randomized if the target INR is ≤ 2.5. For patients requiring deep injection of VO, the INR must be \\\u003C1.5 at the time of injection.\n\nI 10. ECOG performance status (PS) 0 to 1 for patients 18 and older or a Lansky PS ≥ 80 for patients 12 to 17 years of age.\n\nI 11. Life expectancy of at least 3 months. I 12. Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least 6 months after the last dose of any study treatment.\n\nI 13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU\u002FL or equivalent units or β hCG within 7 days before the first dose of study treatment.\n\nI 14. Capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form (ICF)\n\nKey Exclusion Criteria:\n\nE 1. Primary mucosal or uveal melanoma. E 2. More than 2 lines of systemic therapy for advanced melanoma. Note: One additional line of anti-PD-1 therapy in the adjuvant or neoadjuvant setting is allowed if the patient was free of treatment and of PD for at least 6 months and subsequently had confirmed PD on an anti-PD-1 and an anti-CTLA-4 antibody therapy administered in the advanced setting.\n\nE 3. Known acute or chronic hepatitis B (defined as hepatitis B surface antigen \\[HBsAg\\] reactive) or known acute or chronic hepatitis C virus (defined as HCV RNA \\[qualitative\\] is detected).\n\nNote: Patients who have been effectively treated are eligible for randomization. Patients must be negative for HBsAg and HCV RNA.\n\nE 4. Known human immunodeficiency virus (HIV) infection. Note: Testing for HIV is not required unless mandated by local health authority or clinically indicated.\n\nE 5. Active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).\n\nNote: Patients with sporadic cold sores may be randomized if no active cold sores are present at the time of first dose of study treatment.\n\nE 6. Had systemic infection requiring IV antibiotics or other serious active infection requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to the first dose.\n\nE 7. Evidence of spinal cord compression or at high risk of spinal cord compression.\n\nE 8. Known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis at time of screening. Patients with known central nervous system metastases are eligible if they have received standard-of-care therapy for central nervous system disease (such as stereotactic radiosurgery or radical surgical resection followed by radiotherapy) and have evidence of disease stability on 2 subsequent scans performed at least at a 4-week interval.\n\nE 9. Serum lactate dehydrogenase (LDH) \\> 2 × ULN. E 10. Major surgery ≤ 2 weeks prior to starting study treatment. Note: Patients must have recovered adequately from all acute complications of all previous procedures prior to randomization.\n\nE 11. Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ (without invasive component) of the prostate, cervix, or breast.\n\nE 12. History of significant cardiac disease including myocarditis or congestive heart failure (defined as New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, cerebral vascular accident, or myocardial infarction within 6 months from first dose of VO.\n\nE 13. History of life-threatening toxicity related to prior immune therapy except those that are unlikely to recur with standard countermeasures (eg, hormone replacement after adrenal crisis).\n\nE 14. History or evidence of psychiatric, substance abuse (including IV substance abuse), or any other clinically significant disorder, condition, or disease (with the exception of those described above) that, in the opinion of the Investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.\n\nE 15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.\n\nE 16. Active, known, or suspected autoimmune disease requiring systemic treatment.\n\nE 17. History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.\n\nE 18. Prior oncolytic virus therapy or other therapy given by intratumoral administration.\n\nE 19. Requires chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).\n\nE 20. Has received a live vaccine within 28 days prior to the first dose of study treatment.\n\nE 21. Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose, whichever is shorter.\n\nE 22. Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment.\n\nE 23. Has received prior radiotherapy within 2 weeks of start of study treatment or has not recovered from radiotherapy.\n\nE 24. Conditions requiring treatment with immunosuppressive doses (\\> 10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy 14 days before randomization.\n\nNote: Patients who require a brief course (≤ 7 days) or corticosteroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded. Physiologic replacement doses of systemic corticosteroids are permitted, only if the dose does not exceed 10 mg\u002Fday prednisone equivalent.\n\nE 25. History of allergy or sensitivity to study drug components (VO, nivolumab, pembrolizumab, or relatlimab) or to cisplatin or carboplatin or paclitaxel (dependent on cohort) or prior monoclonal antibody treatment.\n\nE 26. Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.\n\nE 27. Is a person who is deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.","12 Years",{"count":225,"type":21},400,[227],"PHASE3","This is a randomized, controlled, multicenter, open-label Phase 3 clinical study comparing VO in combination with nivolumab versus Physician's Choice treatment for patients with unresectable Stage IIIb-IV cutaneous melanoma whose disease progressed on an anti PD-1 and an anti-CTLA-4 containing regimen (administered either as a combination regimen or in sequence) or who are not candidates for treatment with an anti-CTLA-4 therapy.",[29],"2026-05-14",{"date":132,"type":36},{"date":233,"type":36},"2024-07-11",{"date":235,"type":21},"2034-08-31",{"name":237,"class":214},"Replimune, Inc.",81,{"id":240,"slug":241,"hasResults":12,"nctId":242,"briefTitle":243,"officialTitle":244,"acronym":4,"eligibilityCriteria":245,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":246,"targetDuration":4,"studyType":22,"phases":248,"briefSummary":249,"conditions":250,"keywords":251,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":258,"lastUpdatePostDateStruct":259,"startDateStruct":260,"completionDateStruct":262,"leadSponsor":264,"locationsCount":266},"100561809","phase-2-a-study-of-fianlimab-cemiplimab-and-ipilimumab-in-people-with-melanoma-100561809","NCT06594991","A Study of Fianlimab, Cemiplimab, and Ipilimumab in People With Melanoma","A Phase 2 Study of Fianlimab, Cemiplimab, and Ipilimumab in Anti-PD-1 Refractory Melanoma","Inclusion Criteria:\n\n* Age ≥ 18 years at the time of informed consent\n* Patient\u002Flegal authorized representative (LAR) must be able to provide informed consent.\n* Patient must have a histologically confirmed diagnosis of locally advanced unresectable stage III\u002FIV or metastatic stage IV cutaneous or mucosal melanoma that has progressed on PD-1\u002FPD-L1 therapy:\n\n  o For Cohort A, the patient's melanoma must have progressed on prior PD-1 monotherapy\n  * For Cohort B, the patient's melanoma must have progressed on prior combination PD-1 + LAG-3 blockade\n  * Note: Intervening lines of targeted therapy, chemotherapy, bispecific (e.g. IMCgp100) and cell-based therapies are permitted between last ICI-based therapy and the start of study therapy\n  * Note: For cohort A, peptide and mRNA vaccines may have been combined with PD-1 monotherapy as long as no other checkpoint inhibitors were concomitantly administered. For cohort B, peptide and mRNA vaccines may have been combined with combined PD-1 + LAG-3 blockade as long as no other checkpoint inhibitors were concomitantly administered Note: Prior PD-1 monotherapy (Cohort A) or PD-1 and LAG-3 blockade (Cohort B) may have been given in the neoadjuvant or adjuvant setting as long as progression is documented within 3 months of the final dose neoadjuvant\u002Fadjuvant therapy\n* Patients must have measurable disease as defined by RECIST v1.1 o Note: Lesions previously injected with Talimogene laherparepvec or other local therapies may not be selected as target lesions unless they have demonstrated subsequent growth after injection\n* If a suitable archival tissue sample is available, the patient must be willing to have this specimen submitted for research. If an archival sample is not available, the patient is still a candidate for the trial, and every reasonable effort will be made to obtain a biopsy if deemed safe\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1\n\n  ° Adequate laboratory function at screening, defined as:\n\n  ° Hemoglobin ≥ 10 gm\u002FdL (≥ 6.2 mmol\u002FL)\n\n  ° Platelet count ≥ 100 × 10\\^9 \u002FL\n\n  °Serum direct bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN. (Total bilirubin \\\u003C 3 mg\u002FdL for subjects with Gilbert's disease)\n* No signs of active coronary ischemia, including ECG changes or elevated troponin if clinically indicated\n* Calculated creatinine clearance (CrCl) ≥30 mL\u002Fmin based on the Cockcroft-Gault equation\n* All immune-related adverse events (irAE's) from prior ICI based therapy must have improved to Grade 1 or lower with the following exception. Patients with stable adrenal insufficiency are eligible as long as 1) they are asymptomatic at the time of consent on a stable steroid replacement regimen and 2) are on daily steroid replacement of 7.5mg prednisone equivalent or less.\n* All women of childbearing potential (WOCBP)\\* or sexually active men must practice highly effective contraception prior to the initial dose\u002Fstart of the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures in women include\n\n  o Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening,\n  * Intrauterine device (IUD),\n  * Intrauterine hormone-releasing system (IUS),\n  * Bilateral tubal ligation,\n  * Vasectomized partner,† and\u002For\n  * Sexual abstinence.‡,§\n* Male study participants with WOCBP partners are required to use condoms unless they are vasectomized† or practice sexual abstinence.‡,§\n* \\* WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to Clinical Trial Facilitation Group (CTFG) guidance. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.\n\n  * Vasectomized partner or vasectomized study participant must have received medical assessment of the surgical success.\n\n    * Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.\n\n      * Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.\n\nExclusion Criteria:\n\n* Uveal melanoma\n* Untreated central nervous system (CNS) metastases or leptomeningeal involvement; patients with brain metastases definitively treated with surgery or stereotactic radiosurgery (SRS) are permitted\n* Receipt of the following prior therapies:\n\n  * For Cohort A: Any prior anti-LAG-3 (e.g., relatlimab) or CTLA-4 (e.g., ipilimumab) directed therapy, unless it was given in the adjuvant or neoadjuvant setting and the last dose was given more than three months prior to disease recurrence\n  * For Cohort B: Any prior CTLA-directed therapy (e.g., ipilimumab), unless it was given in the adjuvant or neoadjuvant setting and the last dose was given more than three months prior to disease recurrence\n* Prior Grade 3 or greater neurologic toxicity associated with a prior line of ICI therapy\n* Any prior myocarditis associated with ICI therapy\n* Prior Grade 3 or greater colitis or enteritis requiring hospitalization\n* Concurrent systemic steroid therapy higher than physiologic dose steroid replacement (\\>7.5 mg\u002Fday of prednisone or equivalent), given within 14 days of starting treatment, or other immunosuppressive medications within 14 days of the start of treatment. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.\n* Receipt of a live vaccine within 30 days of planned start of study medication\n* Significant infection requiring systemic antibiotics within 2 weeks of the planned start of study medication (e.g., pneumonia, cellulitis)\n* Uncontrolled (i.e., unstable) concomitant medical condition or organ system dysfunction which, in the treating Investigator's opinion, could compromise the patient's safety or compliance with the study procedures.\n* Other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the treating investigator\n* History of severe hypersensitivity reactions to any unknown allergens or any components of the study drugs (active ingredients or excipients)\n* Has uncontrolled infection with human immunodeficiency virus, hepatitis B, or hepatitis C infection; or has a diagnosis of immunodeficiency. Notes:\n\n  * Patients will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV) at screening.\n  * Patients with known HIV infection who have controlled infection (undetectable viral load (HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.\n  * Patients with hepatitis B (HBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.\n  * Patients who are hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) may be enrolled into the study.\n* Patients who are breastfeeding or who are pregnant as evidenced by a positive serum pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of HCG) performed within 14 days of the first dose of study drug.\n* Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific circumstances where local regulations permit, a person who has been imprisoned may be permitted to continue as a participant.)\n* Participants who are compulsorily detained for treatment of either a psychiatric or physical illness (e.g., transmissible infection)",{"count":247,"type":21},88,[203],"The purpose of this study is to test whether the combination of fianlimab, cemiplimab, and ipilimumab is a safe and effective treatment that causes few or mild side effects for locally advanced or metastatic, unresectable, refractory melanoma.",[29],[252,253,254,255,256,257],"Fianlimab","Cemiplimab","Ipilimumab","anti-PD-1 refractory melanoma","unresectable Stage III\u002FIV melanoma","24-166","2026-05-13",{"date":230,"type":36},{"date":261,"type":36},"2024-09-10",{"date":263,"type":21},"2027-09",{"name":265,"class":43},"Memorial Sloan Kettering Cancer Center",12,{"id":268,"slug":269,"hasResults":12,"nctId":270,"briefTitle":271,"officialTitle":272,"acronym":273,"eligibilityCriteria":274,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":275,"targetDuration":4,"studyType":22,"phases":277,"briefSummary":278,"conditions":279,"keywords":282,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":288,"lastUpdatePostDateStruct":289,"startDateStruct":290,"completionDateStruct":292,"leadSponsor":294,"locationsCount":44},"100584471","phase-1-ny-eso-1-redirected-t-cells-in-patients-with-advanced-melanoma-and-sarcoma-100584471","NCT06889766","NY-ESO-1-redirected T Cells in Patients With Advanced Melanoma and Sarcoma","A Phase I Study Evaluating Safety and Feasibility of Redirected Autologous T Cells Expressing a High Affinity TCR Specific for NY-ESO-1 (LauT-1) in Patients With Advanced Melanoma and Sarcoma","LauT1","Inclusion criteria at pre-screening\n\n1\\) Patients with histologically confirmed advanced or metastatic cutaneous melanoma or any type of sarcoma.\n\nInclusion criteria at screening\n\n1. Patients with sarcoma, who have received at least one line of standard therapy (if available) and failed to respond, progressed or were intolerant to that therapy, will be eligible. If the participant refuses or is, in the opinion of the investigator, ineligible for these treatments, the reason must be documented in the medical record.\n2. Patients with metastatic melanoma:\n\n   1. Without proto-oncogene B-Raf (BRAF) mutation who have received at least one line of standard therapy and failed to respond, progressed or were intolerant to that therapy, will be eligible. If the participant refuses or is, in the opinion of the investigator, ineligible for these treatments, the reason must be documented in the medical record.\n   2. With BRAF mutation who have received at least two lines of standard therapy and failed to respond, progressed or were intolerant to that therapy, will be eligible. If the participant refuses or is, in the opinion of the investigator, ineligible for these treatments, the reason must be documented in the medical record.\n3. Patient must have immunohistochemically documented NY-ESO-1 expression, defined as ≥ 1+ expression on either archival or fresh tumor tissue by immunohistochemistry, in ≥50% of the sampled tumor tissue AND HLA-A\\*0201 and\u002For HLA-A\\*0205 positive, as identified by high-resolution genomic deoxyribonucleic acid (DNA) typing of the HLA-A locus.\n4. Age ≥ 18 years\n5. Able to undergo apheresis\n6. At least one lesion accessible to biopsy for translational research (TR) at D30, without putting the patient at unusual risk.\n7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n8. Life expectancy of greater than 12 weeks.\n9. Radiologically measurable disease (as per RECIST v1.1).\n10. Adequate organ function\n\nExclusion Criteria:\n\n1. Patients with an active second malignancy\n2. Patients with symptomatic and\u002For untreated brain metastases, as well as leptomeningeal carcinomatosis. Patients with definitively treated brain metastases will be considered for enrolment after agreement with the Principal Investigator, as long as lesions are stable, there are no new brain lesions, and the patient does not require chronic corticosteroid treatment.\n3. History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin). History of radiation pneumonitis in the radiation field (fibrosis) is allowed.\n4. History of recent myocardial infarction, or unstable angina, within six months prior to enrolment\n5. Patients with prior allogeneic stem cell transplantation or organ transplantation\n6. Active severe systemic infections within 2 weeks prior to apheresis\n7. Patient requiring regular systemic immunosuppressive therapy. All immunosuppressive medications including but not limited to steroids, mycophenolate mofetil, azathioprine, methotrexate, thalidomide, and anti-Tumor Necrosis Factor-alpha (TNF-alpha) agents must have been discontinued at least 2 weeks before apheresis .\n8. History of severe immediate hypersensitivity reaction to any of the agents\u002F excipients of the study products.\n9. Women who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.\n10. Subjects, for whom there are concerns that they will not reliably comply with the requirements for contraception, should not be enrolled into the study.\n11. Any serious underlying medical condition that could interfere with study medication and potential adverse events.",{"count":276,"type":21},9,[57],"A single center, dose escalaion, Phase I clinical trial to demonstrate safety and efficacy of LauT-1, autologous \"New York Esophageal Squamous Cell Carcinoma-1 T-Cell Receptor (NY-ESO-1 TCR)-directed T cells in combination with non-myeloablative (NMA) lymphodepleting chemotherapy and low dose irradiation (LDI) in patients with NY-ESO-1 positive sarcoma and melanoma.",[29,280,281],"Melanoma Metastatic","Sarcoma",[283,284,285,286,281,287],"NY-ESO-1","LauT-1","TCR redirected T cell","metastatic melanoma","autolog T-cell","2026-05-12",{"date":132,"type":36},{"date":291,"type":36},"2025-03-24",{"date":293,"type":21},"2029-06",{"name":295,"class":43},"Centre Hospitalier Universitaire Vaudois",{"id":297,"slug":298,"hasResults":12,"nctId":299,"briefTitle":300,"officialTitle":301,"acronym":4,"eligibilityCriteria":302,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":303,"enrollmentInfo":304,"targetDuration":4,"studyType":22,"phases":306,"briefSummary":307,"conditions":308,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":309,"lastUpdatePostDateStruct":310,"startDateStruct":311,"completionDateStruct":313,"leadSponsor":314,"locationsCount":316},"100616836","phase-2-a-phase-ii-trial-of-lm103-in-advanced-melanoma-100616836","NCT07310784","A Phase II Trial of LM103 in Advanced Melanoma","A Multicenter, Randomized, Controlled, Open-label, Phase II Trial on Autologous Tumor Infiltrating Lymphocyte Injection (LM103 TILs) for the Treatment of Advanced Melanoma","Inclusion Criteria:\n\n* At the date of signing Informed Consent Form (ICF), 18 \\~75 years old, male or female;\n* Expected survival time \\>3 months;\n* ECOG performance status 0-1;\n* Patients with unresectable recurrent\u002Fmetastatic melanoma (excluding uveal melanoma) who have failed at least two lines of standard treatment: • Patients need to have failed or be intolerant to PD-1 antibody treatment; • If the BRAF V600 mutation is positive, treatment with BRAF±MEK inhibitors must fail; • If the NRAS mutation is positive, treatment with Tunlametinib must fail;\n* Patients have lesions that can be used for surgical resection or biopsy puncture;\n* Even after tumor tissue resection\u002Fbiopsy puncture, there should still be at least one measurable lesion (according to RECIST1.1);\n* Patients have sufficient hematology and organ functions;\n* Voluntarily sign a written informed consent form (ICF).\n\nExclusion Criteria:\n\n* A history of other malignant tumors within the past 5 years, excluding malignant tumors that can be expected to heal after treatment (including but not limited to well-treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated by radical surgery);\n* Adverse reactions caused by previous treatments have not been recovered to grade ≤1(CTCAE V5.0) (excluding the laboratory tests from the inclusion criteria, alopecia and neurotoxicity, and hypothyroidism, adrenal insufficiency and hypopituitarism that cannot be restored to grade 2 as determined by the investigators for a long time);\n* Any immune-related adverse reaction (irAE) with a severity level greater than grade 3 that has occurred during any previous immunotherapy and has been permanently discontinued;\n* Have received vaccination within two months prior to tumor tissue procurement surgery, or plan to receive vaccination during the study;\n* Have received TIL cell therapy, allogeneic T cell therapy or NK cell therapy within 6 months prior to signing the ICF;\n* Have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation in the past;\n* Suffering from central nervous system metastases and\u002For cancerous meningitis. Patients who have received brain metastasis treatment and whose conditions have been stable for at least 6 months, and there is no evidence of new or expanded brain metastases may consider participating in this study;\n* Suffering from or suspected of having an active autoimmune disease;\n* Suffering from a large amount of pleural effusion or ascites with clinical symptoms or requiring symptomatic treatment;\n* Patients with current or previous irreversible interstitial lung disease;\n* Suffering from serious cardiovascular and cerebrovascular diseases;\n* Suffering from an active infection that requires systemic treatment;\n* Suffering from infectious diseases such as hepatitis B, hepatitis C, syphilis, AIDS;\n* Patients with esophageal or gastric varices requiring immediate intervention (such as ligation or sclerotherapy), or those with a higher risk of bleeding as recommended by the investigator or gastroenterologist or hepatologist, evidence of portal hypertension (including splenomegaly found in imaging examinations), or a history of variceal bleeding must undergo endoscopic assessment within 3 months before enrollment;\n* Uncontrolled metabolic disorders, such as diabetes, or other non-malignant organ or systemic diseases or secondary reactions to cancer, can lead to higher medical risks and\u002For uncertainties in survival assessment;\n* Those who are known to be allergic to any component of the investigational drug and the LM103 product formula;\n* Women who are pregnant or breastfeeding;\n* As determined by the investigators, there are other severe, acute or chronic medical diseases, mental disorders or laboratory abnormalities that may increase the risks related to participation in the study or may interfere with the interpretation of the study results.","75 Years",{"count":305,"type":21},92,[203],"A total of 92 subjects with advanced melanoma who met the inclusion criteria will be randomly assigned in a 1:1 ratio to the experimental group and the control group in this phase II trial. The study will be followed up until 24 months after treatment.",[29],"2026-05-09",{"date":288,"type":36},{"date":312,"type":36},"2025-12-16",{"date":112,"type":21},{"name":315,"class":214},"Suzhou BlueHorse Therapeutics Co., Ltd.",13,{"id":318,"slug":319,"hasResults":12,"nctId":320,"briefTitle":321,"officialTitle":322,"acronym":4,"eligibilityCriteria":323,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":324,"targetDuration":4,"studyType":22,"phases":326,"briefSummary":327,"conditions":328,"keywords":329,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":332,"lastUpdatePostDateStruct":333,"startDateStruct":335,"completionDateStruct":337,"leadSponsor":339,"locationsCount":341},"100569673","phase-2-safety-and-efficacy-of-eik1001-in-combo-with-pembro-versus-placebo-and-pembro-as-first-line-therapy-in-patients-with-advanced-melanoma-100569673","NCT06697301","Safety and Efficacy of EIK1001 in Combo With Pembro Versus Placebo and Pembro as First-Line Therapy in Patients With Advanced Melanoma.","A Multicenter, Randomized, Double-Blind, Active Comparator-Controlled, Adaptive Phase 2\u002F3 Study to Evaluate the Safety and Efficacy of EIK1001 and Pembrolizumab Versus Placebo and Pembrolizumab as First-Line Therapy in Participants With Advanced Melanoma (TeLuRide-006)","Inclusion Criteria:\n\nTo be eligible for inclusion in this study, participants must:\n\n* Be ≥ 18 years of age on the day of signing of informed consent.\n* Have a life expectancy of at least 3 months.\n* Have histologically or cytologically confirmed Stage 3 (unresectable) or Stage 4 metastatic melanoma per AJCC 8th ed. and be eligible for standard therapy with pembrolizumab.\n* Have at least 1 lesion with measurable disease at Baseline by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by assessment of local site Investigator\u002Fradiologist.\n* Have known BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutional standards during the screening period\n* Have completed prior radiotherapy at least 2 weeks prior to study treatment administration.\n* Have an ECOG Performance Status of 0 to 1.\n* Have adequate organ and marrow function as defined by normal CBC, coagulation, serum chemistry and liver function tests on specimens collected within 10 days of treatment start.\n* Have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication (applies to women of childbearing potential \\[WOCBP\\]).\n* Be willing to use either 2 adequate methods of contraception, 1 adequate method plus a hormonal method of contraception, or be willing to abstain from heterosexual activity throughout the study (Visit 1 to 120 days after the last dose of study therapy; applies to WOCBP who are not menopausal for \\> 2 years, post-hysterectomy\u002Foophorectomy, or surgically sterilized).\n* Agree to use an approved adequate contraceptive method throughout the study (Visit 1 to 120 days after the last dose of study therapy; applies to sexually active male participants with a partner who is WOCBP).\n* Be willing and able to provide written, informed consent for the study.\n\nExclusion Criteria:\n\nA participant is excluded from the study if any of the following criteria apply:\n\n* Has melanoma of ocular origin.\n* Is currently enrolled in or has recently participated in a study of an IMP and received an IMP within 4 weeks or 5 half-lives (whichever is shorter) of administration of EIK1001 or placebo.\n* Prior to the 1St dose of EIK1001 or placebo, the prospective participant has received systemic therapy for advanced melanoma.\n* Note: prior adjuvant or neoadjuvant melanoma therapies (such as anti-PD-1 or anti CTLA 4 therapies or BRAF\u002FMEK inhibitors) are permitted if all related AEs have either returned to Baseline or stabilized, with a minimum of 6 months between the last dose of prior therapy and documented disease progression.\n* Experienced a ≥ Grade 3 AE while receiving prior anti PD 1 therapy.\n* Has had major surgery (\\\u003C 3 weeks prior to the first dose).\n* Has received a live-virus vaccination within 30 days of the first dose of study treatment.\n* Has a known history of prior malignancy, unless the participant has undergone potentially curative therapy with no evidence of disease recurrence for 5 years.\n* Has known active CNS metastases and\u002For carcinomatous meningitis. Participants with previously treated brain metastases may participate if they are clinically stable for at least 4 weeks with no evidence of new or enlarging brain metastases. There must be no need for immunosuppressive doses of glucocorticoids for at least 2 weeks prior to study treatment administration.\n* There is a mean resting QTcF \\> 470 ms on triplicate electrocardiograms.\n* There is active autoimmune disease that has required systemic treatment in the past 2 years. The following autoimmune conditions are permitted: Type 1 diabetes, hypothyroidism (on hormone replacement), or- vitiligo, psoriasis and alopecia as long as no systemic treatment is required.\n* There is either chronic treatment with systemic steroids, other immunosuppressive medication, or either of these has been administered within 14 days of start of study treatment.\n* Note: Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections are eligible. Steroid replacement for adrenal insufficiency is also permitted.\n* There is a history of (noninfectious) pneumonitis\u002Finterstitial lung disease that required steroids or has current pneumonitis\u002F interstitial lung disease.\n* There are any active infections requiring therapy.\n* There is uncontrolled human immunodeficiency virus (HIV) infection. HIV-infected participants with well-controlled HIV may enroll.\n* There is a positive test result for hepatitis B virus (HBV) or HCV indicating presence of virus (it is expected that all participants will have been serologically tested for hepatitis B in advance of this study, with HBsAG, anti-HBc IgG, and anti-HBs as per ASCO 2020 Provisional Clinical Opinion \\[PCO\\] on universal Serologic testing for hepatitis B at the onset of anticancer therapy; screening should also include an anti-HCV test prior to start of cancer treatment:\n* There is a history or clinical evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study or interfere with the participant's participation for the full duration of the study\n* Known psychiatric or substance abuse disorder that would interfere with cooperation with study requirements.\n* There is a known history of regular illicit drug use and\u002For recent history (within the last year) of substance abuse (including alcohol).\n* Participant is pregnant, breastfeeding, or planning to conceive or father children within the projected duration of the study.\n* Participant is currently receiving medications known to be strong inhibitors or inducers of CYP3A4 and CYP1A2.",{"count":325,"type":21},740,[203,227],"The study is for patients with advanced melanoma who are eligible for standard therapy with Pembrolizumab.",[29],[330,331],"Metastatic","Advanced","2026-05-06",{"date":334,"type":36},"2026-05-08",{"date":336,"type":36},"2025-05-22",{"date":338,"type":21},"2040-12",{"name":340,"class":214},"Eikon Therapeutics",107,{"id":343,"slug":344,"hasResults":12,"nctId":345,"briefTitle":346,"officialTitle":347,"acronym":4,"eligibilityCriteria":348,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":349,"targetDuration":4,"studyType":22,"phases":351,"briefSummary":352,"conditions":353,"keywords":354,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":366,"lastUpdatePostDateStruct":367,"startDateStruct":369,"completionDateStruct":371,"leadSponsor":373,"locationsCount":375},"100638950","phase-4-melchrono-a-prospective-randomized-study-investigating-chrono-immunotherapy-for-advanced-melanoma-100638950","NCT07574047","MELCHRONO: A Prospective Randomized Study Investigating Chrono-immunotherapy for Advanced Melanoma.","MELCHRONO: A Prospective Randomized Study Investigating Chrono-immunotherapy for Advanced Melanoma. A Phase IV Trial.","Inclusion Criteria:\n\n* Written informed consent according to Swiss law and ICH GCP E6 regulations before registration and prior to any trial specific procedures.\n* Histologically confirmed unresectable cutaneous stage III or stage IV melanoma. Note: Participants with central nervous system (CNS) metastases are eligible.\n* Participants with a previously treated other malignancy are eligible, if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low.\n* Measurable or evaluable disease.\n* Age ≥ 18 years.\n* Patients deemed suitable for ICI therapy based on the local investigator's clinical assessment.\n* ECOG performance status 0-2.\n* Women of childbearing potential must use effective contraception , not be pregnant or lactating and agree not to become pregnant during trial treatment and until 5 months after the last dose of trial treatment. A negative pregnancy test before inclusion into the trial is required for all women of childbearing potential.\n* Men agree not to donate sperm or to father a child during trial treatment and until 5 months after the last dose of trial treatment.\n\nExclusion Criteria:\n\n* Prior treatment with any systemic anti-cancer therapy; with the exception of prior adjuvant anti-PD-1 or BRAF\u002FMEK inhibitor therapy if the time from last dose to recurrence is more than 6 months.\n* Recent treatment (within 28 days prior to first dose) with any experimental drug.\n* Known history of allogeneic organ transplant.\n* Uveal or mucosal melanoma.\n* Receipt of live attenuated vaccine within 28 days prior to first dose.\n* Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information.\n* Known hypersensitivity to trial drug(s) or to any component of the trial drug(s).\n* Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect participant compliance or place the participant at high risk from treatment-related complications.",{"count":350,"type":21},108,[84],"Melanoma remains a common cancer with rising incidence, and despite significant improvements with immune checkpoint inhibitors (ICIs), clinical outcomes remain heterogeneous. Retrospective analyses across multiple tumor types, including melanoma, suggest that earlier daytime administration of ICIs may enhance therapeutic effectiveness, potentially due to circadian modulation of immune function. A pronounced survival benefit has been observed particularly among female patients receiving earlier infusions. This trial prospectively evaluates whether aligning ICI administration with circadian immune activity can improve outcomes in melanoma and support the development of sex-specific optimization of immunotherapy.",[31,29],[355,356,357,358,254,359,360,361,362,363,364,365],"Advanced melanoma","chrono-immunotherapy","phase IV","Nivolumab","relatlimab","Pembrplizumab","Opdivo","Keytruda","Opdualag","Yervoy","immune checkpoint inhibitor","2026-05-01",{"date":368,"type":36},"2026-05-07",{"date":370,"type":21},"2026-09",{"date":372,"type":21},"2032-06",{"name":374,"class":43},"Swiss Cancer Institute",8,{"id":377,"slug":378,"hasResults":12,"nctId":379,"briefTitle":380,"officialTitle":381,"acronym":4,"eligibilityCriteria":382,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":383,"targetDuration":4,"studyType":22,"phases":385,"briefSummary":386,"conditions":387,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":366,"lastUpdatePostDateStruct":388,"startDateStruct":389,"completionDateStruct":391,"leadSponsor":393,"locationsCount":44},"100636219","phase-1-au-tmp-and-radiotherapy-for-advanced-melanoma-with-anti-pd-1-therapy-100636219","NCT07562841","Au-TMP and Radiotherapy for Advanced Melanoma With Anti-PD-1 Therapy","Safety and Tolerability of Au-TMP Nanoparticles in Combination With Radiotherapy for Patients With Advanced Melanoma Receiving Anti-PD-1 Therapy","Inclusion Criteria:\n\n1. Age: Age ≥ 18 years.\n2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n3. Histologically confirmed unresectable Stage III or Stage IV melanoma without prior systemic therapy. Prior adjuvant or neoadjuvant therapy is permitted, provided it was completed at least 3 weeks before enrollment and all related adverse events (AEs) have resolved to baseline or NCI CTCAE v5.0 Grade ≤ 1.\n4. Presence of at least one measurable lesion according to RECIST v1.1 criteria.\n5. At least one lesion suitable for intratumoral injection and radiotherapy (located in the skin, subcutaneous tissue, superficial lymph nodes, or visceral lesions assessed as safe for access) that has not received prior radiotherapy (unless documented progression has occurred).\n6. Adequate hematologic and organ function within 7 days prior to the first dose, including:\n\n   Hematology: Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹\u002FL; Platelet count (PLT) ≥ 90 × 10⁹\u002FL; Hemoglobin (Hb) ≥ 90 g\u002FL. (No Granulocyte-Colony Stimulating Factor (G-CSF), platelet transfusion, or Erythropoietin (EPO)\u002FRed Blood Cell (RBC) transfusion within 14 days prior to testing).\n\n   Renal Function: Serum creatinine (Cr) ≤ 1.5 × Upper Limit of Normal (ULN), or calculated creatinine clearance (Ccr) ≥ 50 mL\u002Fmin using the Cockcroft-Gault formula.\n\n   Hepatic Function: Total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3.0 × ULN for patients with Gilbert's Syndrome or liver metastases); Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP) ≤ 2.5 × ULN (≤ 5.0 × ULN for patients with documented liver or bone metastases); Serum albumin ≥ 2.8 g\u002FdL.\n\n   Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN.\n\n   Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 50%.\n7. Anticipated survival time ≥ 16 weeks.\n8. Agreement to use highly effective contraception methods during the trial and for 12 months after the last dose of treatment.\n9. Voluntarily participate in the study, sign the Informed Consent Form (ICF), demonstrate good compliance, and be willing to cooperate with follow-up.\n\nExclusion Criteria:\n\n1. Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.\n2. Known hypersensitivity to recombinant humanized anti-PD-1 monoclonal antibodies or any of their components.\n3. Active skin breakdown, infection, ulceration, necrosis, bleeding at the injection site, or a high risk of hollow organ perforation.\n4. Known allergy or intolerance to Au-TMP active ingredients, excipients, or similar compounds.\n5. Presence of known driver mutations (e.g., BRAF V600E\u002FK, c-KIT, NRAS) for which targeted therapies are already approved and available as first-line treatment.\n6. Ocular (uveal) or mucosal melanoma.\n7. Receipt of other anti-tumor therapies (including corticosteroids or immunotherapy) or participation in other clinical trials within 4 weeks before treatment initiation; failure to recover from toxicities of prior therapies (except Grade 2 alopecia and Grade 1 neurotoxicity).\n8. Pregnant or breastfeeding women.\n9. Positive for Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV). Patients with positive Hepatitis B Surface Antigen (HBsAg) or Hepatitis B Core Antibody (HBcAb) must have a negative Hepatitis B Virus (HBV) DNA test (quantitative detection \\\u003C 500 IU\u002FmL).\n10. History of active tuberculosis.\n11. Active autoimmune disease requiring systemic treatment within the past 2 years (except physiological replacement therapy for thyroid, insulin, or adrenal\u002Fpituitary insufficiency).\n12. Serious uncontrolled concurrent medical conditions, including uncontrolled diabetes, interstitial lung disease, New York Heart Association (NYHA) Class III\u002FIV heart failure, severe cardiac arrhythmias, or recent (within 6 months) myocardial infarction or cerebrovascular accidents.\n13. Active Central Nervous System (CNS) or leptomeningeal metastases. Patients with treated brain metastases are eligible if they are stable (no progression via Magnetic Resonance Imaging (MRI)) for at least 8 weeks post-treatment and 28 days prior to the first dose, and do not require immunosuppressive doses of corticosteroids (\\>10 mg\u002Fday prednisone equivalent) for at least 2 weeks.\n14. Receipt of hematopoietic stimulants (e.g., G-CSF, EPO) within 2 weeks prior to treatment.\n15. Receipt of live vaccines within 4 weeks prior to treatment.\n16. Major surgery (excluding diagnostic procedures) within 4 weeks prior to treatment.\n17. History of psychiatric disorders or persistent drug\u002Fsubstance abuse.\n18. Other malignancies within the past 5 years, except for successfully treated localized cancers such as basal\u002Fsquamous cell skin cancer or in situ carcinomas (cervix, breast, prostate).\n19. Any other acute or chronic medical\u002Fpsychiatric condition or laboratory abnormality that, in the investigator's opinion, increases research-related risk or interferes with the interpretation of study results.\n20. Any condition that is not in the best interest of the participant.",{"count":384,"type":21},6,[57],"Advanced melanoma is a highly aggressive malignancy that frequently exhibits resistance to conventional radiotherapy and single-agent immunotherapy. This study aims to evaluate the safety and tolerability of an innovative melanoma-specific aggregable gold nanosystem (Au-TMP) in patients with advanced melanoma. This single-arm, open-label, Phase 1a clinical trial utilizes a dose-escalation design, where participants receive a single intratumoral injection of Au-TMP followed by sequential radiotherapy and Toripalimab (anti-PD-1) treatment. This trial aims at assessing the safety of intratumoral injection of Au-TMP and radiotherapy in combination with anti-PD-1 therapy.",[29],{"date":368,"type":36},{"date":390,"type":21},"2026-04-28",{"date":392,"type":21},"2029-04-30",{"name":394,"class":43},"West China Hospital",{"id":396,"slug":397,"hasResults":12,"nctId":398,"briefTitle":399,"officialTitle":400,"acronym":4,"eligibilityCriteria":401,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":402,"targetDuration":4,"studyType":22,"phases":404,"briefSummary":405,"conditions":406,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":407,"lastUpdatePostDateStruct":408,"startDateStruct":410,"completionDateStruct":412,"leadSponsor":414,"locationsCount":73},"100631754","phase-4-ctdna-guided-addition-of-ipilimumab-to-patients-receiving-nivolumab-and-relatlimab-100631754","NCT07504796","ctDNA-guided Addition of Ipilimumab to Patients Receiving Nivolumab and Relatlimab","A Multi-center Trial Evaluating the ctDNA-guided Addition of Ipilimumab to Patients Receiving Nivolumab and Relatlimab for Advanced Melanoma","Inclusion Criteria:\n\n1. Patient must be ≥ 18 years old.\n2. Patients must have signed and dated an Institutional Review Board (IRB)\u002FIndependent Ethics Committee (IEC)-approved written informed consent from (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.\n3. Patients must be willing and able to comply with scheduled visits, laboratory tests, and other requirements of the study.\n4. Patient must have active advanced melanoma, defined as unresectable stage IIIB-IV by American Joint Committee on Cancer (AJCC) 8th edition. Patients with mucosal melanoma defined as unresectable stage III or regional\u002Fdistant metastatic disease are eligible.\n5. Patient must have melanoma originating from cutaneous, acral-lentiginous, or mucosal primary sites. Patients with melanoma of unknown primary site are eligible.\n6. Patient must have at least one lesion for measurable disease per RECIST 1.1 guidelines (refer to section 8.1 for more information).\n7. Patients must have specimen required for study procedures, including either archived tumor tissue or fresh tissue and whole blood available, at baseline to send to Natera as part of screening for Signatera testing to be completed. (refer to section 8.2 for more information)\n8. Patient must be planned to initiate standard of care first-line therapy for metastatic disease\n9. Patients must not have received prior anticancer treatment for metastatic disease (for example, but not limited to, systemic, local, radiation, radiopharmaceutical). Exceptions: Surgery for melanoma and\u002For post-resection brain radiotherapy (RT) if central nervous system (CNS) metastases and adjuvant RT for locoregional disease after resection. Prior treatment with the following therapies in the adjuvant setting: interferon (IFN)-alpha therapy, BRAF\u002FMEK therapy (e.g. dabrafenib and trametinib), anti-PD-1 therapy (e.g. pembrolizumab or nivolumab), or anti-CTLA-4 therapy (e.g. ipilimumab) is allowed if therapy has been completed for 6 months (see criterion 10).\n10. All patients must have their disease status documented by a complete physical examination and imaging studies within 4 weeks prior to the first dose of study drug. Imaging studies must include computerized tomography (CT) scan of chest, abdomen, pelvis, and all known sites of resected disease in the setting of Stage IIIB\u002FC\u002FD or Stage IV disease, and brain magnetic resonance imaging (\\[MRI\\]; brain CT is allowable if MRI is contraindicated).\n11. The complete set of baseline radiographic images must be available before treatment initiation. Prior treatment with adjuvant IFN-alpha, adjuvant ipilimumab and\u002For nivolumab or pembrolizumab or BRAF\u002FMEK therapy (e.g. dabrafenib and trametinib) are allowed if recurrence of disease occurred more than 6 months from the last dose of adjuvant therapy; that is, a patient must have recurred with unresectable disease at least 6 months or more after finishing adjuvant therapy; combination adjuvant therapies with nivolumab or pembrolizumab are also allowed (vaccines, bempegaldesleukin, relatlimab, etc.).\n12. Patients must have detectable ctDNA at baseline. A blood sample will be collected during the screening phase in order to determine if patients are eligible based on presence of ctDNA. Patients are permitted to start treatment with nivolumab\u002Frelatlimab cycle 1 while awaiting results.\n13. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n14. Patients with prior or concurrent nonmelanoma malignancies whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study.\n15. Asymptomatic brain metastases are permitted. Patients who have received\u002Fwill receive gamma knife radiotherapy or stereotactic body radiation therapy (SBRT) treated lesions are also eligible. Patients must be on \\\u003C 10 mg of prednisone or equivalent at the time of treatment.\n16. All baseline laboratory requirements will be assessed and should be obtained within 14 days of C1D1. Screening laboratory values must meet the following criteria:\n\n    * white blood cells (WBCs) ≥ 2000\u002FμL\n    * Neutrophils ≥ 1500\u002FμL\n    * Platelets ≥ 100 × 10³\u002FμL\n    * Hemoglobin ≥ 9.0 g\u002FdL\n    * Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance \\> 40 mL\u002Fminute (using Cockcroft\u002FGault formula)\n    * Aspartate Aminotransferase (AST) ≤ 1.5 × ULN\n    * Alanine Aminotransferase (ALT) ≤ 1.5 × ULN\n    * Total bilirubin ≤ 1.5 × ULN (except patients with Gilbert Syndrome who must have total bilirubin \\\u003C 3.0 mg\u002FdL)\n    * Coagulation : Prothrombin Time (PT), Partial Thromboplastin Time (PTT), International Normalized Ratio (INR)\n\nExclusion Criteria:\n\n1. Patients with carcinomatosis meningitis or a history of current ocular\u002Fuveal melanoma are excluded.\n2. Patients with a history of myocarditis.\n3. Patients with active, known, or suspected autoimmune disease requiring immunosuppression beyond 10 mg daily of prednisone. Patients with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the Principal Investigator be consulted prior to signing informed consent.\n4. Patients with a condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of C1D1. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.\n5. Patients must not be receiving concurrent anti-tumor therapies in addition to the standard of care anti-PD-1 regimens. Patients who are receiving bisphosphonates and RANKL inhibitors for management of bone metastases are eligible.\n6. Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with or would otherwise affect study participation.\n7. Known hypersensitivity to monoclonal antibodies\n8. Pregnancy\n9. Prior therapy for melanoma with the following exceptions which are allowed: 1) surgery for the melanoma lesion(s), 2) adjuvant RT after neurosurgical resection for CNS lesions or for resected locoregional disease, and 3) prior adjuvant therapy as long as concluded 6 months prior.\n10. Any of the following laboratory abnormalities:\n\n    * Absolute Neutrophil Count (ANC) \\\u003C 1,500\u002FμL or WBC \\\u003C 2,000 μL\n    * Platelet count \\\u003C 100,000\u002FμL\n    * Hematologic growth factors are not allowed at screening or during the first cycle of treatment\n    * Hemoglobin \\\u003C 9 g\u002FdL (\\\u003C 5.5 mmol\u002FL; previous red blood cell (RBC) transfusion is permitted)\n    * Creatinine \\> 1.5 × ULN\n    * AST or ALT \\> 1.5 × ULN. For patients with liver metastasis AST or ALT \\> 3 × ULN\n    * Serum total bilirubin \\> 1.5 mg\u002FdL or \\> 3 × ULN for patients with hereditary benign hyperbilirubinemia",{"count":403,"type":21},90,[84],"The purpose of this study is to investigate the use of ctDNA measurements to guide first-lien therapy choice for patients with advanced or metastatic melanoma. Primary endpoints include progression-free survival. Secondary study endpoints include objective response rate and incidence and severity of immune-related adverse events.",[98,29],"2026-04-17",{"date":409,"type":36},"2026-04-21",{"date":411,"type":36},"2026-04-13",{"date":413,"type":21},"2031-05",{"name":415,"class":43},"NYU Langone Health",{"id":417,"slug":418,"hasResults":12,"nctId":419,"briefTitle":420,"officialTitle":421,"acronym":4,"eligibilityCriteria":422,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":423,"targetDuration":4,"studyType":22,"phases":425,"briefSummary":426,"conditions":427,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":466,"lastUpdatePostDateStruct":467,"startDateStruct":469,"completionDateStruct":471,"leadSponsor":473,"locationsCount":44},"100513775","phase-2-at-home-cancer-directed-therapy-versus-in-clinic-for-the-treatment-of-patients-with-advanced-cancer-100513775","NCT05969860","At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer","Cancer CARE Beyond Walls - A Pilot of a Randomized, Pragmatic Trial of Cancer Directed Therapy Administration in the Patients' Homes Versus in Clinic","Inclusion Criteria:\n\n* Female or male patients with histologically confirmed malignancy. Patients with hepatocellular carcinoma (HCC) are eligible based on imaging diagnosis along; histologic confirmation is not required.\n* Participant must be receiving a standard-of-care treatment regimen listed in this protocol that is being used in accordance with standard medical practice. Specifically, it must be either a) FDA-approved for the participant's disease indication, or b) recommended in nationally recognized professional guidelines (e.g. NCCN, ASCO, ASH, etc.) as standard of care for the disease indication. Off-label use is permitted only if supported by such guidelines.\n\n  * Note, patients diagnosed with any of the following disease types may receive any of the eligible regimens listed. Additionally, patients receiving immunotherapy, such as nivolumab or pembrolizumab, may receive these infusions in home supplemental to any of the regimens identified. Patients may receive any combination of any above listed medications or regimens:\n  * Eligible disease cancer types:\n\n    * Anal cancer\n    * Appendiceal carcinoma\n    * Basal cell carcinoma\n    * Bladder cancer\n    * Biliary cancer\n    * Breast cancer\n    * Central Nervous System malignancy including glioblastoma\n    * Cervical cancer\n    * Cholangiocarcinoma\n    * Colorectal carcinoma\n    * Endometrial cancer\n    * Fallopian tube cancer\n    * Gastroesophageal cancer \\[including gastric, esophageal, and gastroesophageal junction (GEJ) cancers\\]\n    * Germ cell carcinoma\n    * Head and Neck cancer\n    * Hepatocellular Carcinoma\n    * Liver\n    * Lung\n    * Lymphoma\n    * Melanoma\n    * Merkel Cell\n    * Multiple Myeloma\n    * Myelodysplastic syndrome\n    * Myeloid Disorders\n    * Neuroendocrine carcinoma\n    * Ovarian cancer\n    * Pancreatic adenocarcinoma\n    * Penile carcinoma\n    * Peritoneal carcinoma\n    * Prostate cancer\n    * Renal cell cancer\n    * Sarcoma\n    * Squamous cell Carcinoma of the Skin\n    * Testicular cancer\n    * Urethral carcinoma\n    * Vaginal carcinoma\n    * Vulvar carcinoma\n  * Eligible Regimens\n\n    * Fluorouracil (5-FU) +\u002F- leucovorin +\u002F- bevacizumab +\u002F- trastuzumab\n    * 5FU +\u002F- leucovorin +\u002F- bevacizumab +\u002F- nivolumab\n    * Atezolizumab +\u002F- bevacizumab\n    * Atezolizumab +\u002F- bevacizumab + cobimetinib, atezolizumab +\u002F- bevacizumab + vemurafenib, atezolizumab +\u002F- bevacizumab + cobimetinib + vemurafenib\n    * Avelumab\n    * Avelumab + axitinib\n    * Bevacizumab\n    * Bevacizumab + capecitabine\n    * Bevacizumab + irinotecan (+\u002F- capecitabine)\n    * Bevacizumab + olaparib, bevacizumab + lenvatinib, bevacizumab + niraparib, bevacizumab + rucaparib\n    * Bevacizumab + Temozolomide, Bevacizumab + Lomustine, or Bevacizumab + everolimus\n    * Bevacizumab + trifluridine\u002Ftipiracil\n    * Bortezomib\n    * Bortezomib + cyclophosphamide, bortezomib + lenalidomide, bortezomib + pomalidomide, bortezomib + selinexor\n    * Bortezomib + venetoclax\n    * Carfilzomib\n    * Carfilzomib + cyclophosphamide, carfilzomib + lenalidomide, carfilzomib + pomalidomide, carfilzomib + selinexor\n    * Carfilzomib + venetoclax\n    * Cemiplimab\n    * Cisplatin\n    * Cisplatin\u002F5-FU\n    * Cisplatin\u002Fetoposide\n    * Cisplatin + durvalumab\n    * Cisplatin + gemcitabine\n    * Cisplatin + gemcitabine + durvalumab\n    * Daratumumab (+ oral \\[PO\\] cyclophosphamide, lenalidomide, pomalidomide, or selinexor)\n    * Daratumumab + bortezomib (+ PO cyclophosphamide, lenalidomide, pomalidomide, or selinexor)\n    * Daratumumab + carfilzomib (+ PO cyclophosphamide, lenalidomide, pomalidomide, or selinexor)\n    * Degarelix\n    * Durvalumab\n    * Durvalumab + tremelimumab\n    * Eribulin\n    * FOLFIRI +\u002F- bevacizumab (5FU +\u002F- leucovorin + irinotecan)\n    * Fam-trastuzumab deruxtecan\n    * Fulvestrant\n    * Fulvestrant + ribociclib, fulvestrant + abemaciclib, fulvestrant + palbociclib, fulvestrant + alpelisib, or fulvestrant + capivasertib\n    * Gemcitabine\n    * Gemcitabine + durvalumab\n    * Gemcitabine + paclitaxel protein-bound\n    * Goserelin acetate\n    * Irinotecan\n    * Irinotecan + capecitabine\n    * Lanreotide\n    * Leuprolide\n    * Nivolumab\n    * Nivolumab + cabozantinib\n    * Nivolumab-relatlimab\n    * Octreotide\n    * Paclitaxel\n    * Pembrolizumab\n    * Pembrolizumab + axitinib, pembrolizumab + lenvatinib, pembrolizumab + capecitabine, pembrolizumab + dabrafenib +\u002F- trametinib, pembrolizumab + trametinib)\n    * Pemetrexed\n    * Pertuzumab\n    * Pemetrexed + pembrolizumab\n    * Rituximab\n    * Trastuzumab + paclitaxel\n    * Trastuzumab with or without pertuzumab maintenance (SQ or IV) (+\u002F- tucatinib +\u002F- capecitabine)\n    * Decitabine\n    * These regimens can be used only if patients are receiving one of the regimens above:\n\n      * Darbepoetin-alfa\n      * Epoetin\n      * Filgrastim\n* Note: Female or male patients with histologically confirmed malignancy who are currently receiving treatment with one of the above eligible regimens may receive supportive care medications for treatment or prevention of bone metastases, including agents such as:\n\n  * Zoledronic acid\n  * Denosumab\n* Patient has had adequate tolerability of their clinical standard of care cancer treatment in the opinion of their treating physician and no drug-related infusion reactions prior to consent\n* Patients who according to documentation from their treating provider plan to continue the treatment regimen they are currently prescribed for at least 24 weeks from the start of cycle following randomization.\n* Residing within the area serviced by supplier and paramedic network\n* Residence has wireless fidelity (wifi) to enable a reliable connection with the remote Command Center or it is suitable for connection through a wireless network solution\n* Age \\>= 18 years at time of registration\n* Signed informed consent form by patient\n* Willing and able to comply with the study protocol in the investigator's judgement\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2\n* Ability to complete questionnaire(s) by themselves or with assistance\n* RANDOMIZATION ELIGIBILITY CRITERIA: In addition to the criteria above, confirmation by the CCBW Command Center that the patient has adequate tolerability to the standard of care cancer therapy and no drug-related infusion reactions since pre-registration and prior to registration\n\nExclusion Criteria:\n\n* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm. Note: Patients are permitted concomitant standard of care oral drugs such as ribociclib, abemaciclib, or palbociclib in combination with endocrine therapy (e.g., Leuprolide, fulvestrant intramuscular \\[IM\\], etc.); tucatinib and capecitabine in combination with trastuzumab and pertuzumab for HER2 positive breast cancer; dexamethasone, cyclophosphamide, lenalidomide or pomalidomide for multiple myeloma; temozolomide, lomustine, or afinitor in combination with avastin for glioblastoma. In addition, all oral anti-hormonal agents for breast and prostate cancer are permitted (e.g., tamoxifen, arimidex, abiraterone, etc.) if used in combination with any of the drugs\n* Requiring 24\u002F7 assistance with activities of daily living (ADLs)\n* Current inpatient hospitalization (excluding admission to the Advanced Care at Home program)\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Cardiac arrhythmia\n  * Myocardial infarction =\\\u003C 6 months\n  * Wound healing disorder\n  * Or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements",{"count":424,"type":21},220,[203],"This clinical trial studies the effect of cancer directed therapy given at-home versus in the clinic for patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Currently most drug-related cancer care is conducted in infusion centers or specialty hospitals, where patients spend many hours a day isolated from family, friends, and familiar surroundings. This separation adds to the physical, emotional, social, and financial burden for patients and their families. The logistics and costs of navigating cancer treatments have become a principal contributor to patients' reduced quality of life. It is therefore important to reduce the burden of cancer in the lives of patients and their caregivers, and a vital aspect of this involves moving beyond traditional hospital and clinic-based care and evaluate innovative care delivery models with virtual capabilities. Providing cancer treatment at-home, versus in the clinic, may help reduce psychological and financial distress and increase treatment compliance, especially for marginalized patients and communities.",[428,87,429,430,431,432,433,434,435,436,437,438,439,440,91,441,442,443,444,445,446,447,448,449,450,149,451,452,89,453,454,455,29,456,457,458,92,459,460,461,462,463,464,465],"Advanced Anal Carcinoma","Advanced Bladder Carcinoma","Advanced Breast Carcinoma","Advanced Carcinoid Tumor","Advanced Cervical Carcinoma","Advanced Colorectal Carcinoma","Advanced Gastric Carcinoma","Advanced Glioblastoma","Advanced Head and Neck Carcinoma","Advanced HER2 Positive Breast Carcinoma","Advanced Lung Carcinoma","Advanced Lung Small Cell Carcinoma","Advanced Malignant Germ Cell Tumor","Advanced Neuroendocrine Carcinoma","Advanced Ovarian Carcinoma","Advanced Pancreatic Carcinoma","Advanced Prostate Small Cell Neuroendocrine Carcinoma","Advanced Prostate Carcinoma","Hematopoietic and Lymphoid System Neoplasm","Multiple Myeloma","Myelodysplastic Syndrome","Advanced Basal Cell Carcinoma","Advanced Cholangiocarcinoma","Advanced Esophageal Carcinoma","Advanced Fallopian Tube Carcinoma","Advanced Liver Carcinoma","Advanced Lymphoma","Advanced Malignant Testicular Neoplasm","Advanced Merkel Cell Carcinoma","Advanced Penile Carcinoma","Advanced Primary Malignant Central Nervous System Neoplasm","Advanced Sarcoma","Advanced Skin Squamous Cell Carcinoma","Advanced Urethral Carcinoma","Advanced Vaginal Carcinoma","Advanced Vulvar Carcinoma","Advanced Appendix Carcinoma","Advanced Gastroesophageal Junction Adenocarcinoma","2026-04-15",{"date":468,"type":36},"2026-04-20",{"date":470,"type":36},"2023-08-23",{"date":472,"type":21},"2027-01-01",{"name":474,"class":43},"Mayo Clinic",{"id":476,"slug":477,"hasResults":12,"nctId":478,"briefTitle":479,"officialTitle":479,"acronym":4,"eligibilityCriteria":480,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":481,"targetDuration":4,"studyType":22,"phases":482,"briefSummary":483,"conditions":484,"keywords":487,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":490,"lastUpdatePostDateStruct":491,"startDateStruct":493,"completionDateStruct":495,"leadSponsor":497,"locationsCount":73},"100538770","phase-2-neoadjuvant-and-adjuvant-anti-pd1-or-combinations-for-locoregionally-advanced-melanoma-100538770","NCT06295159","Neoadjuvant and Adjuvant Anti-PD1 or Combinations for Locoregionally Advanced Melanoma","Inclusion Criteria:\n\n* This study is divided into 2 sub-studies\u002Fparts designated Part 1 and Part 2 that will enroll in sequence starting with Part 1 followed by Part 2. In Part 2, Part 2 Cohort A and Part 2 Cohort B will enroll simultaneously. Inclusion criteria apply to Part 1 and Part 2 unless otherwise specified.\n* Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.\n* 18 years of age or older\n* Histologic diagnosis of melanoma (cutaneous, acral, mucosal or unknown primary) belonging to the following American Joint Committee on Cancer (AJCC) 8th edition TNM stages (Tx or T1-4) and (N1b, N1c, N2b, N2c, N3b or N3c) and\u002For (M1a).\n* Requirements for prior systemic therapy for melanoma are as follows:\n\n  1. Sub-study Part 1: No prior systemic therapy for melanoma (N=30).\n  2. Sub-study Part 2 Cohort A: No prior systemic therapy for melanoma (N=20)\n  3. Sub-study Part 2 Cohort B: Locoregionally advanced melanoma that is refractory to systemic adjuvant therapy (anti-PD1-based or BRAF-MEK inhibitors) (N=40).\n\nThis excludes patients who previously received adjuvant or neoadjuvant anti-PD1 plus anti-LAG3 or anti-PD1 plus anti-CTLA4.\n\nParticipants who experienced progression or recurrence after anti-PD1 as monotherapy or other combinations or after BRAF-MEK inhibition would be eligible.\n\nParticipants who have previously experienced prior high-grade (grade 3 or 4 by CTCAE criteria) immune related adverse events with immune checkpoint inhibitors are not eligible.\n\n* Must be considered surgically operable and may present as any of the following groups:\n\n  1. Primary melanoma with clinically apparent regional lymph node metastases, confirmed by pathological diagnosis.\n  2. Clinically detected recurrence of melanoma at regional lymph node basin(s), confirmed by pathological diagnosis.\n  3. Clinically or histologically detected primary melanoma involving multiple regional nodal groups, confirmed by pathological diagnosis.\n  4. Clinically detected single site of nodal metastatic melanoma arising from an unknown primary, confirmed by pathological diagnosis.\n  5. Participants with in-transit or satellite metastases with or without lymph node involvement are allowed if they are considered surgically resectable at Screening by the treating surgical oncologist.\n  6. Participants with distant cutaneous\u002Fsubcutaneous, soft tissue or nodal metastases with or without regional lymph node involvement are allowed if they are considered potentially surgically resectable and can be biopsied at Screening by the treating surgical oncologist. Elevated LDH is not an exclusion.\n  7. Elevated LDH is not an exclusion.\n* Participants are eligible for this study either at presentation for primary melanoma with concurrent regional nodal and\u002For in-transit or distant metastasis, or at the time of clinically detected nodal, in transit, or distant recurrence.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Adequate organ function within 28 days of Cycle 1 Day 1 (C1D1)\n* Participants must provide a sufficient and adequate formalin-fixed paraffin-embedded (FFPE) tumor tissue sample from the most recent biopsy of a tumor lesion, obtained within 90 days from signing informed consent form (ICF). If recent tumor tissue is unavailable or inadequate, a fresh biopsy will be required, unless the principal investigator agrees that it is not safe\u002Ffeasible.\n* Participants must be evaluated by standard-of-care full body imaging studies, the choice of which is decided by the treating physician investigator.\n* Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study medication) in accordance with the standard of care for WOCBP.\n* WOCBP must agree to use highly effective contraceptive measures starting with the screening visit through 5 months after the last dose of study treatment. Highly effective contraception is as stipulated in national or local guidelines.\n* Male participants with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the screening visit through 5 months after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.\n* Willing and able to comply with the requirements of the protocol.\n\nExclusion Criteria:\n\n* Pregnancy or lactation.\n* Treatment with another investigational drug or other systemic intervention for melanoma within 4 weeks of initiation of study drugs. Patients must not have radiotherapy within the preceding 2 weeks. Patients must have recovered from adverse events due to agents administered more than 4 weeks earlier.\n* Participants must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery and be free of significant detectable infection.\n* Ocular or uveal melanoma.\n* Bowel obstruction or impending bowel obstruction within the past 3 months.\n* Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident\u002Fstroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure or serious uncontrolled cardiac arrhythmia requiring medication.\n* Active or history of brain metastases or leptomeningeal metastases.\n* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment, i.e., patients with a history of prior malignancy are eligible if treatment was completed at least 2 years before the first dose of study treatment and the patient has no evidence of disease. Participants with history of prior early-stage basal\u002Fsquamous cell skin cancer, low-risk prostate cancer eligible for active surveillance or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible.\n* Treatment with one of the following classes of drugs within the delineated time window prior to C1D1:\n\n  1. Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.\n  2. mAbs, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.\n  3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster \\\u003C 7 days before C1D1. For vaccines requiring more than 1 dose, the full series should be completed prior to C1D1, when feasible. Booster shot not required but also must be administered \\> 7 days from C1D1 or \\> 7 days from future cycle on study.\n* Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.\n* Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.\n* History of allogeneic organ transplant.\n* Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.\n* Participants with a condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.\n* Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs.\n* History or current evidence of any condition, co-morbidity, therapy, any active infections, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.\n* Pregnant or breastfeeding or WOCBP who are not willing to employ effective birth control from screening to 5 months after the last dose of study treatment (whichever is later).\n* Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe\u002Fcritical illness prior to C1D1.\n* Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required.\n* Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Patients who are receiving or who have received anti-HBV therapy and have undetectable HBV DNA for at least 6 months prior to study entry are eligible. Serological testing for HBV at screening is not required. Known active co-infection with hepatitis B and hepatitis C or with hepatitis B and hepatitis D is an exclusion.\n* Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for HCV at screening is not required.\n* Dependence on total parenteral nutrition.\n* Troponin T (TnT) or I (TnI) \\> 2× institutional ULN. Participants with TnT or TnI levels between \\> 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤ 1 × ULN. If TnT or TnI levels are between \\>1 to 2 × ULN within 24 hours, the participant must undergo a cardiology consultation and cardiac evaluation and be considered for treatment, based on a favorable benefit\u002Frisk assessment by the Investigator. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are \\\u003C 2 × ULN, the participant must undergo a cardiology consultation and cardiac evaluation and be considered for treatment, based on a favorable benefit-risk assessment by the Investigator.\n* Left ventricular ejection fraction (LVEF) assessment with documented LVEF \\\u003C 50% by either transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) scan (TTE preferred test) within 6 months prior to start of study treatment.\n* Participants with a history of myocarditis and\u002For current diagnosis of myocarditis, regardless of etiology.\n* Participants must not have a history of allergy or hypersensitivity to study intervention components.",{"count":403,"type":21},[203],"The purpose of this study is to determine if neoadjuvant (treatment before surgery) immunotherapy treatment based on tumor biomarkers results in better participant outcomes. Immunotherapy is the treatment of disease by using a person's own immune system.\n\nThis study is divided into 2 sub-studies\u002Fparts designated Part 1 and Part 2 that will enroll in sequence starting with Part 1 followed by Part 2.",[485,486,29,31],"Melanoma Stage III","Melanoma Stage IV",[31,488,489],"Anti-PD1","Locoregionally Advanced Melanoma","2026-03-31",{"date":492,"type":36},"2026-04-01",{"date":494,"type":36},"2024-05-17",{"date":496,"type":21},"2028-11",{"name":498,"class":43},"H. Lee Moffitt Cancer Center and Research Institute",{"id":500,"slug":501,"hasResults":12,"nctId":502,"briefTitle":503,"officialTitle":504,"acronym":505,"eligibilityCriteria":506,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":507,"targetDuration":4,"studyType":22,"phases":509,"briefSummary":510,"conditions":511,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":512,"lastUpdatePostDateStruct":513,"startDateStruct":515,"completionDateStruct":517,"leadSponsor":519,"locationsCount":521},"100524713","phase-3-imc-f106c-regimen-versus-nivolumab-regimens-in-previously-untreated-advanced-melanoma-prism-mel-301-100524713","NCT06112314","IMC-F106C Regimen Versus Nivolumab Regimens in Previously Untreated Advanced Melanoma (PRISM-MEL-301)","A Phase 3 Randomized, Controlled Study of IMC-F106C Plus Nivolumab Versus Nivolumab Regimens in HLA-A*02:01-Positive Participants With Previously Untreated Advanced Melanoma (PRISM-MEL-301","PRISM-MEL-301","Inclusion Criteria:\n\n* Participants must be HLA-A\\*02:01-positive\n* Participants must have histologically confirmed Stage IV or unresectable Stage III melanoma\n* Archived or fresh tumor tissue sample that must be confirmed as adequate\n* Participants must have measurable disease per RECIST 1.1\n* Participant must have BRAF V600 mutation status determined\n* Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1\n* Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the study screening date until 5 months after the final dose of study intervention\n\nExclusion Criteria:\n\n* Participants with a history of a malignant disease other than those being treated in this study\n* Participants with untreated, active, or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis\n* Hypersensitivity to IMC-F106C, nivolumab, relatlimab, or any associated excipients\n* Participants with clinically significant pulmonary disease or impaired lung function\n* Participants with clinically significant cardiac disease or impaired cardiac function\n* Participants with active autoimmune disease requiring immunosuppressive treatment\n* Participants with any medical condition that is poorly controlled or that would, in the Investigator's or Sponsor's judgment, adversely impact the participant's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results\n* Participants who received prior systemic anticancer therapy for unresectable or metastatic melanoma\n* Participants with a history of a life-threatening AE related to prior anti-PD-(L)1 or anti-LAG-3",{"count":508,"type":21},680,[227],"This is a phase 3, randomized, controlled study of brenetafusp (IMC-F106C) plus nivolumab compared to standard nivolumab regimens in HLA-A\\*02:01-positive participants with previously untreated advanced melanoma.",[29],"2026-02-23",{"date":514,"type":36},"2026-02-25",{"date":516,"type":36},"2024-06-05",{"date":518,"type":21},"2027-10-16",{"name":520,"class":214},"Immunocore Ltd",211,{"id":523,"slug":524,"hasResults":12,"nctId":525,"briefTitle":526,"officialTitle":527,"acronym":4,"eligibilityCriteria":528,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":529,"targetDuration":4,"studyType":22,"phases":531,"briefSummary":532,"conditions":533,"keywords":534,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":512,"lastUpdatePostDateStruct":551,"startDateStruct":552,"completionDateStruct":554,"leadSponsor":556,"locationsCount":557},"100481461","phase-3-tebentafusp-regimen-versus-investigators-choice-in-previously-treated-advanced-melanoma-tebe-am-100481461","NCT05549297","Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)","Phase 2\u002F3 Randomized Study of Tebentafusp as Monotherapy and in Combination With Pembrolizumab Versus Investigator's Choice in HLA-A*02:01-positive Participants With Previously Treated Advanced Melanoma (TEBE-AM)","Inclusion Criteria:\n\n* HLA-A\\*02:01-positive\n* unresectable Stage III or Stage IV non-ocular melanoma\n* archival tumor tissue sample or a newly obtained biopsy of a tumor lesion not previously irradiated has been provided.\n* measurable or non-measurable disease per RECIST 1.1\n* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1\n* If applicable, must agree to use highly effective contraception\n* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent (ICF) and protocol\n* Must agree to provide protocol specified samples for biomarker analyses.\n\nExclusion Criteria:\n\n* Pregnant or lactating women\n* diagnosis of ocular or metastatic uveal melanoma\n* history of a malignant disease other than those being treated in this study\n* ineligible to be retreated with pembrolizumab due to a treatment-related AE\n* known untreated or symptomatic central nervous system (CNS) metastases and\u002For carcinomatous meningitis\n* previous severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)\n* active autoimmune disease requiring immunosuppressive treatment\n* known psychiatric or substance abuse disorders\n* received prior treatment with a licensed or investigative Immune-mobilizing monoclonal T-cell receptor Against Cancer (ImmTAC) medication or who have not completed adequate washout from prior medications.\n* received chemotherapy or biological cancer therapy (excluding anti-PD(L)1 mAb, ipilimumab, and BRAF TKI regimen) within 14 days of first dose\n* received cellular therapies within 90 days of study intervention\n* ongoing Common Terminology Criteria for Adverse Events(CTCAE) Grade ≥ 2 clinically significant who in the opinion of the investigator could affect the outcome of the study\n* received systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of first dose\n* have not progressed on treatment with an anti-PD(L)1 mAb\n* have not received prior treatment with an approved anti-CTLA-4 mAb\n* have a BRAF V600 mutation, who have not received a prior BRAF\u002FMEK TKI regimen\n* currently participating or have participated in a study of an investigational agent or using an investigational device within 30 days of the first dose\n* known history of chronic viral infections such as hepatitis B virus (HBV) or hepatitis C virus (HCV)\n* known clinically significant pulmonary or cardiac disease or impaired lung or cardiac function\n* Out of range Laboratory values\n* history of allogenic tissue\u002Fsolid organ transplant",{"count":530,"type":21},540,[227],"The purpose of this study is to evaluate the efficacy and safety of tebentafusp-based regimens, including tebentafusp monotherapy and in combination with anti-PD1 vs investigator choice (including clinical trials of investigational agents, salvage therapy per local standard of care \\[SoC\\], best supportive care \\[BSC\\] on protocol survivor follow up) in patients with advanced non-ocular melanoma.",[29],[31,535,536,537,538,539,540,541,542,543,544,545,546,547,548,549,550],"IMCgp100","Tebentafusp","Cutaneous Melanoma","Immunotherapy","gp100","TCR","Pembrolizumab","Bispecific T cell receptor fusion protein","ImmTAC (Immune-mobilizing monoclonal T-cell receptor Against Cancer)","Immune mobilizing monoclonal T cell receptor against cancer","KIMMTRAK","Acral Melanoma","Mucosal Melanoma","Blue Nevus","anti-PDL1","checkpoint therapy",{"date":514,"type":36},{"date":553,"type":36},"2022-12-19",{"date":555,"type":21},"2028-07",{"name":520,"class":214},82,{"id":559,"slug":560,"hasResults":12,"nctId":561,"briefTitle":562,"officialTitle":563,"acronym":4,"eligibilityCriteria":564,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":565,"targetDuration":4,"studyType":22,"phases":567,"briefSummary":568,"conditions":569,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":570,"lastUpdatePostDateStruct":571,"startDateStruct":573,"completionDateStruct":575,"leadSponsor":577,"locationsCount":579},"100532542","phase-1-a-clinical-study-of-t3011-in-subjects-with-advanced-melanoma-100532542","NCT06214156","A Clinical Study of T3011 in Subjects With Advanced Melanoma","A Phase Ib\u002FIIa Clinical Study to Evaluate the Tolerability, Safety and Preliminary Efficacy of T3011 in Subjects With Advanced Melanoma","Inclusion Criteria:\n\n1. Subjects with advanced melanoma;\n2. At least one measurable lesion;\n3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;\n4. Expected survival \\> 12 weeks;\n5. Laboratory inspection meets the requirements;\n6. For women of childbearing potential, the serum pregnancy test results must be negative within 7 days prior to the first dose，and effective contraceptive measures must be taken from signing the informed consent form (ICF) until at least 6 months after the last dose;\n7. Male subjects of childbearing potential agree to use effective contraception from signing the ICF until at least 6 months after the last dose; In addition, male subjects must agree not to donate sperm during this period;\n8. Understand and voluntarily sign the ICF，willing and able to comply with all experimental requirements.\n\nExclusion Criteria:\n\n1. Subjects who have received other antitumor therapy within the prescribed time prior to the first dose;\n2. Subjects with a history of other malignancies within the prescribed time prior to the start of study treatment.\n3. At screening, subjects with a history or evidence of high risk cardiovascular disease;\n4. Subjects with persistent or active infection requiring intravenous anti-infective therapy;\n5. Subjects with autoimmune diseases or a history of autoimmune diseases;\n6. Subjects with known psychiatric disorders that may affect trial compliance;\n7. Subjects who have pleural effusion, pericardial effusion, or ascites before starting treatment and require puncture drainage, or who had received puncture drainage within the specified time before starting the study treatment;\n8. Subjects requiring systemic treatment with anti-HSV drugs during the study period;\n9. Subjects who have received live or attenuated vaccines within the prescribed time prior to the first dose, or who plan to receive such vaccines during the study period; Subjects who have received any tumor vaccine in the past;\n10. Subjects who had undergone major surgery within the prescribed time before the first dose，and had not recovered from surgery-related adverse reactions or were still in the postoperative recovery period，or who plan to undergo major surgery during the study period;\n11. Subjects with a history of drug use，drug abuse or alcohol abuse within the year prior to signing the ICF;\n12. Female subjects who are pregnant or breastfeeding, or planning to conceive or have children during the study period;\n13. The investigator considers it inappropriate to participate in this study.",{"count":566,"type":21},42,[57,203],"This clinical study evaluated the tolerability, safety and preliminary efficacy of T3011 in subjects with advanced melanoma.",[29],"2026-01-12",{"date":572,"type":36},"2026-01-14",{"date":574,"type":36},"2024-01-26",{"date":576,"type":21},"2026-09-30",{"name":578,"class":214},"Shanghai Pharmaceuticals Holding Co., Ltd",7,{"id":581,"slug":582,"hasResults":12,"nctId":583,"briefTitle":584,"officialTitle":585,"acronym":4,"eligibilityCriteria":586,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":303,"enrollmentInfo":587,"targetDuration":4,"studyType":22,"phases":588,"briefSummary":590,"conditions":591,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":595,"lastUpdatePostDateStruct":596,"startDateStruct":598,"completionDateStruct":600,"leadSponsor":602,"locationsCount":73},"100446803","early-phase-1-a-study-of-gc101-til-in-advanced-melanoma-10hospital-100446803","NCT05098184","A Study of GC101 TIL in Advanced Melanoma (10hospital)","A Clinical Study to Evaluate the Safety and Efficacy of Autologous Tumor Infiltrating Lymphocytes Injection in Patients With Advanced Melanoma","Inclusion Criteria:\n\n1. Age: 18 years to 75 years;\n2. Histologically diagnosed as primary\u002Frelapsed\u002Fmetastasized melanoma;\n3. Expected life-span more than 3 months;\n4. Karnofsky≥60% or ECOG score 0-2;\n5. Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.\n6. Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated;\n7. At least 1 evaluable tumor lesion;\n8. Hematology and Chemistry（within 7 days prior to enrollment）:\n\n   * Absolute count of white blood cells≥2.5×10\\^9\u002FL;\n   * Absolute count of neutropils≥1.5×10\\^9\u002FL;\n   * Absolute count of lymphocytes ≥0.7×109\u002FL；\n   * Platelet count≥100×10\\^9；\n   * hemoglobin≥90 g\u002FL;\n   * Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);\n   * International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);\n   * Serum creatinine ≤1.5mg\u002FdL(or ≤132.6μmol\u002FL), or clearance rate≥50mL\u002Fmin;\n   * Serum ALT\u002FAST ≤3×ULN(subjects with liver metastasis ≤3×ULN);\n   * Totol bilirubin≤1.5×ULN;\n9. no absolute or relative contraindications to operation or biopsy;\n10. Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion；\n11. Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs;\n12. Be able to understand and sign the informed consent document;\n13. Be able to stick to follow-up visit plan and other requirements in the agreement.\n\nExclusion Criteria:\n\n1. Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment;\n2. Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%;\n3. Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc.\n4. Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and\u002For anti-HCV positive), syphilis infection or Treponema pallidum antibody positive;\n5. Severe physical or mental diseases;\n6. Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection);\n7. Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;\n8. History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy;\n9. Having received immunotherapy and developed irAE level greater than Level 3;\n10. Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded);\n11. Females in pregnancy or lactation;\n12. History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy;\n13. Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.",{"count":55,"type":21},[589],"EARLY_PHASE1","This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma. Autologous TILs are expanded from tumor resections or biopsies and infused i.v. into the patient after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.",[29,592,593,594],"Tumor Infiltrating Lymphocyte","Treatment Side Effects","Effects of Immunotherapy","2025-12-04",{"date":597,"type":36},"2025-12-11",{"date":599,"type":36},"2021-09-26",{"date":601,"type":21},"2026-09-25",{"name":603,"class":214},"Shanghai Juncell Therapeutics",{"id":605,"slug":606,"hasResults":12,"nctId":607,"briefTitle":608,"officialTitle":609,"acronym":610,"eligibilityCriteria":611,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":612,"targetDuration":4,"studyType":22,"phases":614,"briefSummary":615,"conditions":616,"keywords":617,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":625,"lastUpdatePostDateStruct":626,"startDateStruct":628,"completionDateStruct":630,"leadSponsor":632,"locationsCount":73},"100552405","early-phase-1-fusa-with-intratumoral-polyiclc-in-regionally-advanced-resectable-melanoma-100552405","NCT06472661","FUSA With Intratumoral PolyICLC in Regionally Advanced Resectable Melanoma","Pilot Evaluation of Focused Ultrasound Ablation and Intratumoral PolyICLC in Patients With Regionally Advanced Resectable Melanoma Who Are Receiving Neoadjuvant Immunotherapy","Mel 70","Inclusion Criteria:\n\n1. Age ≥18 years.\n2. Diagnosis of advanced melanoma planned for surgical resection.\n3. Focused Ultrasound Ablation (FUSA): The targeted lesion(s) must be visible by ultrasound imaging and meet the following criteria.\n\n   Note: Brain lesions may not be targeted for treatment.\n   1. Approximately 1 cm (or more) diameter of treatable tumor volume for lesions to be treated with FUSA.\n   2. The target treatment area needs to be contained within a region at least 5 mm from the skin surface and less than or equal to 23 mm from the skin surface.\n\n      The target treatment area must be at a safe distance from all critical structures, including but not limited to ribs or other bony structures, vital organs, named blood vessels or nerves.\n   3. The critical structures, with the exception of the skin, will not be in the pre-focal ultrasound path. This will be considered at enrollment and confirmed immediately prior to treatment.\n   4. The anterior-posterior dimension of the treatment area by US should be no less than 9 mm.\n4. A subjects target lesion must be amenable to intratumoral injection with polyICLC per the treating clinician's discretion.\n5. Subjects must be receiving checkpoint blockade (either monotherapy or combination therapy) at the time of registration.\n6. Biopsies:\n\n   Note: Biopsies may be completed with or without image guidance.\n\n   Lesions that have been selected for focused ultrasound may have been previously radiated provided:\n   * The tumor site that was previously radiated has progressed.\n   * A baseline biopsy of the tumor site is obtained following progression and prior to study entry.\n7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.\n8. Subjects with known brain metastases may participate if all of the following are true:\n\n   * There has been no evident growth of any brain metastasis since the most recent treatment\n   * No brain metastasis is \\> 2 cm in diameter at the time of registration.\n   * Neurologic symptoms have returned to baseline,\n   * There is no evidence of new or enlarging brain metastases,\n   * Subjects are not using steroids for at least 7 days prior to registration, except as allowed in Section 5.2. Regardless of dose, however, subjects who are on a steroid taper for management of brain metastases are not eligible until 7 days after completion of that steroid taper.\n9. Ability and willingness to give informed consent.\n\nExclusion Criteria:\n\n1. Any of the following medications or treatments are administered to the subject within 4 weeks of study day 1:\n\n   1. Radiation therapy (Note: Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week prior to registration)\n   2. Allergy desensitization injections\n   3. High doses of systemic corticosteroids, with the following qualifications and exceptions:\n\n      * Daily doses of 10 mg or less prednisone (or equivalent) per day administered parenterally or orally are allowed in patients with normal adrenal and pituitary function.\n      * In patients with adrenal or pituitary insufficiency replacement steroid doses are allowed.\n      * Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are permitted at low doses (less than 500 mcg fluticasone per day, or equivalent) 41,42\n      * Topical and nasal corticosteroids are acceptable.\n   4. Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)\n   5. Interleukins (e.g. Proleukin®)\n   6. Any investigational therapeutic agent.\n   7. Targeted therapies specific for mutated BRAF or for MEK\n   8. Live vaccine\n   9. Interferon (e.g. Intron-A®)\n   10. Cytotoxic chemotherapy for cancer\n2. Subject has a known addiction to alcohol or drugs and is actively taking those agents, or has recently (within 1 year) taken these agents or has ongoing illicit IV drug use.\n3. Subject is known to be HIV positive or has evidence of active Hepatitis B or C virus, unless:\n\n   * The subject has HIV but has been taking antiretroviral therapy, and agrees to take antiretroviral therapy throughout the study\n   * The subject has active Hepatitis B or C but does not have a detectable viral load\n4. Pregnancy or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test (urinary or serum beta-HCG) obtained within 2 weeks prior to registration. Males and females must agree, in the consent form, to use effective birth control methods during the course of treatment and following treatment in accordance with the labeling guidelines for each approved therapy.\n5. Medical contraindications or potential problems that prevent compliance with the requirements of the protocol in the opinion of the investigator.\n6. Active infection requiring systemic therapy.\n7. The presence of Class III or IV heart disease as classified according to the New York Heart Association.\n8. Previous treatment with polyICLC within 4 weeks. If a subject was previously treated with intratumoral polyICLC and experienced a significant (grade ≥3) toxicity related to the polyICLC treatment, the tumor that was treated should not be re-treated as part of this protocol.",{"count":613,"type":21},11,[589],"This study is for adult patients with advanced melanoma who are receiving immunotherapy and who are planning on having surgery for their cancer. All participants in this study will receive an experimental treatment made up of focused ultrasound ablation (FUSA), a non-invasive experimental treatment that uses ultrasound waves to heat and destroy tumor tissue, and an injection in the tumor with an experimental drug that activates the immune system called polyICLC (polyinosinic-polycytidylic acid that is stabilized with carboxymethylcellulose and polylysine). Neither the drug nor the device that are used in this study have been approved by the U.S. Food and Drug Administration (FDA).",[29],[31,29,618,619,620,621,622,623,624],"Focused Ultrasound","polyICLC","poly ICLC","poly-ICLC","Echopulse","Echopulse HD","Focused Ultrasound Ablation","2025-11-19",{"date":627,"type":36},"2025-11-20",{"date":629,"type":36},"2024-09-27",{"date":631,"type":21},"2026-08",{"name":633,"class":43},"University of Virginia",{"id":635,"slug":636,"hasResults":12,"nctId":637,"briefTitle":638,"officialTitle":639,"acronym":4,"eligibilityCriteria":640,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":641,"targetDuration":4,"studyType":22,"phases":642,"briefSummary":643,"conditions":644,"keywords":645,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":657,"lastUpdatePostDateStruct":658,"startDateStruct":660,"completionDateStruct":662,"leadSponsor":664,"locationsCount":73},"100513685","phase-1-naltrexone-and-propranolol-combined-with-immunotherapy-100513685","NCT05968690","Naltrexone and Propranolol Combined With Immunotherapy","A Phase I Study to Evaluate the Safety of Naltrexone and Propranolol in Combination With Standard of Care Ipilimumab and Nivolumab in Patients With Advanced Melanoma","Inclusion Criteria:\n\n* Age of 18 years or older and able to understand and sign the informed consent form.\n* Histologically confirmed diagnosis of unresectable stage III or stage IV melanoma.\n* Candidate for standard of care therapy with ipilimumab 3 mg\u002Fkg + nivolumab 1 mg\u002Fkg.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n* Treatment-naïve or has received any number of prior lines of therapy. Prior targeted therapy is allowed, but small molecule inhibitors must be discontinued within two weeks before starting the study.\n* Life expectancy of at least 6 months.\n* Presence of at least one accessible site of disease to provide an on-study biopsy for tumor tissue. The biopsy may be waived after discussion with the Principal Investigator (PI) if it is deemed unfeasible. The site may be a target lesion as long as it will not be rendered unmeasurable by the biopsy procedure.\n* Willingness to undergo tumor biopsy (if archival tumor is not available) prior to initiation of therapy and while on the study.\n* Willingness to provide an archival specimen block, if available, for research purposes.\n* Normal organ function, defined as:\n\n  1. Absolute neutrophil count (ANC) \\>1500\u002FmcL\n  2. Platelets \\>100,000\u002FmcL\n  3. Hemoglobin (Hb) \\>9 g\u002FdL\n  4. Albumin \\>2.5 mg\u002FdL\n  5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C2.5 times the upper limit of normal (ULN)\n  6. Serum total bilirubin \\\u003C1.5 times ULN or direct bilirubin \\\u003C ULN for subjects with total bilirubin levels \\>1.5 times ULN.\n* Female participants of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.\n* Female participants of childbearing potential should be willing to use a highly effective form of contraception (hormonal or intrauterine device) along with a condom in their male partner, or be surgically sterile, or abstain from heterosexual activity for a period of at least six months after the last dose of study medication.\n* Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through at least six months after the last dose of study drug.\n* Participants must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Tumor sites situated in a previously irradiated area or in an area subjected to other loco-regional therapy are not considered measurable unless there has been demonstrated progression in the lesion.\n* Prior focal radiotherapy is allowed.\n\nExclusion Criteria:\n\n* Presence of untreated brain metastases, unless discussed with the Principal Investigator (PI) and meet specific criteria for inclusion (treatment-naïve patients with brain metastases \\\u003C10 mm, asymptomatic, without significant edema, hemorrhage, shift, or requirement for steroids or anti-seizure medications, and not in eloquent areas). These patients may potentially forego initial local treatment of the brain metastases and have them reassessed after consultation with the Neurosurgery and Radiation Oncology teams.\n* Use of corticosteroids to control immune-related adverse events at enrollment. Participants who previously required corticosteroids for symptom control must be off steroids for at least two weeks. Low-dose steroid use (=10 mg of prednisone or equivalent) as corticosteroid replacement therapy for primary or secondary adrenal insufficiency is allowed.\n* Failure to recover (i.e., Grade 1 or at baseline) from adverse events due to prior treatment.\n* History of grade 3-4 neurologic or cardiac toxicity or life-threatening liver toxicity poorly responsive to steroids with prior anti-PD-1 therapy.\n* Presence of leptomeningeal disease.\n* Active autoimmune disease unrelated to the use of immune checkpoint inhibitors that has required systemic treatment in the past year (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.\n* Contraindications to the use of propranolol, including:\n\n  1. Cardiogenic shock.\n  2. Sinus bradycardia greater than first-degree block.\n  3. Severe bronchial asthma.\n  4. Known hypersensitivity to propranolol.\n  5. Requirement for current use of an alternative beta-blocker.\n  6. Uncontrolled diabetes.\n  7. Uncontrolled depression.\n  8. Unstable angina or myocardial infarction within 3 months of Day 1 Cycle 1.\n* For enrollment into Cohort 2-4 ONLY: Contraindications to the use of naltrexone, including:\n\n  1. Participants currently receiving opioid analgesics or anticipated to require opioid analgesics in the near future.\n  2. Participants currently dependent on opioids, including those currently maintained on opiate agonists (e.g., methadone) or partial agonists (e.g., buprenorphine).\n  3. Participants in acute opioid withdrawal.\n  4. Individuals with a history of sensitivity to naltrexone.\n* Pregnancy or breastfeeding. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately. Breastfeeding must be discontinued if the mother is enrolled in this trial due to the potential risk for adverse events in nursing infants.\n* Receipt of any other investigational agents or participation in a study of an investigational agent or use of an investigational device within four weeks of the first dose of treatment.\n* Concurrent condition (including medical illness, active infection requiring treatment with intravenous antibiotics, or presence of laboratory abnormalities) or history of a prior condition that places the patient at unacceptable risk if treated with the study drug or confounds the ability to interpret data from the study.\n* Concurrent, active malignancies in addition to those being studied, except for cutaneous squamous cell carcinoma or basal cell carcinoma.\n* Active (non-infectious) pneumonitis.\n* Hepatitis B (HBV) or Hepatitis C (HCV) acute or chronic infection.\n* Receipt of a live vaccine",{"count":266,"type":21},[57],"Various forms of stress can promote cancer development and growth and negatively impact the immune system's response to tumors. Beta-adrenergic and opioid receptors co-exist in many cells including immune cells and are integral components of the body's response to stress. Pre-clinical studies have demonstrated that dual blockade of these receptors can decrease tumor growth and modulate the anti-tumor immune response. This clinical trial investigates the safety and potential therapeutic benefits of combining a beta-adrenergic blocker (propranolol) and an opioid receptor antagonist (naltrexone) with immune checkpoint inhibitors in patients with advanced melanoma.",[29],[31,646,647,648,649,650,651,652,653,654,655,656,538,254,358],"Metastatic melanoma","Skin cancer","Immune checkpoint inhibitors","Propranolol","Naltrexone","Beta-adrenergic blocker","Opioid receptor antagonist","Tumor microenvironment","NK cells","T-cells","Combination therapy","2025-09-12",{"date":659,"type":36},"2025-09-18",{"date":661,"type":36},"2023-09-11",{"date":663,"type":21},"2027-09-30",{"name":665,"class":43},"Sarah Weiss",{"id":667,"slug":668,"hasResults":12,"nctId":669,"briefTitle":670,"officialTitle":671,"acronym":4,"eligibilityCriteria":672,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":673,"targetDuration":4,"studyType":22,"phases":675,"briefSummary":676,"conditions":677,"keywords":678,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":681,"startDateStruct":682,"completionDateStruct":684,"leadSponsor":686,"locationsCount":73},"100487627","phase-1-memory-like-natural-killer-cells-with-nivolumab-and-relatlimab-in-advanced-or-metastatic-melanoma-after-progression-on-checkpoint-inhibitors-100487627","NCT05629546","Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors","Phase I Study of Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors","Inclusion Criteria:\n\n* Diagnosis of histologically confirmed advanced or metastatic melanoma that has progressed after at least 12 weeks or a minimum of 2 doses of treatment with a standard of care PD1\u002FPDL1 containing therapy (nivolumab, pembrolizumab, atezolizumab, or durvalumab).\n* Age: ≥18 years of age\n* Have an Eastern Cooperative Oncology Group Performance Status (ECOG) ≤ 2 at screening Form Arm 1 only: Patients must meet the eligibility criteria to undergo apheresis to obtain autlogous NK cells.\n* For Arm 2 only: Patient must have an available allogeneic NK cell donor who meets the eligibility criteria.\n* Adequate organ function as defined below:\n\n  * Total bilirubin \\\u003C 2 mg\u002FdL\n  * AST(SGOT)\u002FALT(SGPT) \\\u003C 3.0 x ULN\n  * Creatinine within normal institutional limits OR creatinine clearance \\> 40 mL\u002Fmin\u002F1.73 m\\^2 by Cockcroft-Gault Formula\n  * Oxygen saturation ≥ 90% on room air\n  * Ejection fraction ≥ 45%\n* Patients with a prior history of symptomatic CNS metastases must have received treatment and be neurologically stable for at least for 4 weeks and off anti-seizure medication and steroids for 7 days prior to initiation of LDC.\n* Able to be off corticosteroids and any other immune suppressive medications for at least 14 days prior to apheresis or lymphodepletion and continuing until 30 days after the infusion of the ML NK cells. However, use of physiological dosing of corticosteroids (defined as ≤15mg prednisone or equivalent) is permitted if deemed medically necessary.\n* Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, throughout participation in the study and for at least 5 months after the last dose of relatlimab.\n* Life expectancy \\>12 weeks\n* Ability to understand and willingness to sign an IRB approved written informed consent document\n\nExclusion Criteria:\n\n* Active autoimmune disorder requiring immunosuppression (physiologic steroids defined as ≤15mg prednisone or equivalent are acceptable).\n* Prior history of an immune-related Grade 3 or 4 AE attributed to prior cancer immunotherapy (other than endocrinopathy managed with either replacement therapy or asymptomatic elevation of serum amylase or lipase) that resulted in permanent discontinuation of the prior immunotherapeutic agent.\n* Patients with Grade ≤2 irAE who have not completely recovered from irAE (i.e. have residual toxicities \\>Grade 1) related to prior cancer immunotherapy (other than endocrinopathy management with replacement therapy or stable vitiligo). Patients treated with corticosteroids for irAE must demonstrate absence of related signs or symptoms for ≥7 days following discontinuation of corticosteroids.\n* Leptomeningeal disease, carcinomatous meningitis, or symptomatic CNS metastases. Patients with asymptomatic brain metastasis with no pending intervention needed, or patients with treated CNS disease and stable for at least 4 weeks and off anti-seizure medication and steroids for 7 days prior to initiation of LDC are eligible.\n* Known hypersensitivity to one or more of the study agents.\n* Comorbidities and any conditions, that in the opinion of the investigator, that put the subject at unacceptable risk for study therapy or prevent the participant from consenting or participating in the study.\n* Uncontrolled and active systemic infections, including but not limited to HIV, Hepatitis B or C infection.\n* Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.\n* New progressive pulmonary infiltrates concerning for new or uncontrolled infectious process. Infiltrates attributed to infection must be stable\u002F improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections).\n* Received any investigational or off-label drugs, or cytotoxic chemotherapy within the 14 days or five half-lives (whichever is greater) prior to apheresis.\n* Pregnant or breastfeeding.\n* Subjects are not acceptable candidates if they received prior tumor infiltrating lymphocytes (TIL) therapy (either in the setting of clinical trial or standard of care if TIL therapy is FDA approved in the future), or an organ allograft.\n* Has a known additional malignancy that is progressing or required active treatment within the past 2 years. Note: participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg. Breast carcinoma, cervical cancer in situ) that has undergone potentially curative therapy are not excluded.\n* Received a live or attenuated vaccine within 28 days prior to the beginning of the lymphodepletion therapy.\n\nEligibility Criteria for Haploidentical Donors (For Arm 2 only)\n\n* Donor must be at least 18 years of age.\n* Donor must be willing, in general good health, and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.\n* Donor must be negative for hepatitis, HTLV, and HIV on donor viral screen.\n* Donor may not be pregnant and\u002For breastfeeding. Women of childbearing potential must have a negative pregnancy test within 30 days prior to apheresis.\n* Donor must be able to understand and willing to sign an IRB-approved written informed consent document.\n* Only haploidentical donors will be included.\n* Donor must meet the requirements of institutional donor guidelines, including the requirements of Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT) criteria.\n\nEligibility Criteria for Autologous Patients (For Arm 1 only)\n\n* Patient must be willing and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.\n* Patient must be negative for hepatitis, HTLV, and HIV on the viral screen.\n* Patient may not be treated with any cytotoxic treatment within 2 weeks prior to leukapheresis.",{"count":674,"type":21},33,[57],"This is a Phase 1 open-label, study designed to characterize the safety, tolerability, and preliminary anti-tumor activity of memory-like natural killer cells (ML NK) in combination with nivolumab and relatlimab in subjects with advanced and\u002For metastatic melanoma. There will be two arms to test the variables of ML NK cell source. ML NK cells from an autologous source will be used for Arm 1, and ML NK cells from an allogeneic source will be used for Arm 2. The investigators hypothesize that ML NK cells from either an autologous source or allogeneic source are safe and tolerable in subjects with advanced and\u002For metastatic melanoma.",[29,98],[679,286,680],"advanced melanoma","checkpoint inhibitor resistant melanoma",{"date":657,"type":36},{"date":683,"type":36},"2024-11-06",{"date":685,"type":21},"2030-11-30",{"name":687,"class":43},"Washington University School of Medicine",{"id":689,"slug":690,"hasResults":12,"nctId":691,"briefTitle":692,"officialTitle":693,"acronym":4,"eligibilityCriteria":694,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":303,"enrollmentInfo":695,"targetDuration":4,"studyType":22,"phases":697,"briefSummary":698,"conditions":699,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":701,"lastUpdatePostDateStruct":702,"startDateStruct":704,"completionDateStruct":706,"leadSponsor":707,"locationsCount":4},"100601183","phase-1-a-clinical-study-of-bt02-for-the-treatment-of-patients-with-advanced-malignant-melanoma-100601183","NCT07107178","A Clinical Study of BT02 for the Treatment of Patients With Advanced Malignant Melanoma","A Phase Ib Study of the Safety, Tolerability and Efficacy of BT02 for the Treatment of Patients With Advanced Malignant Melanoma","Inclusion Criteria:\n\n1. Patients with histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic malignant melanoma (except for uveal melanoma) who have failed in the prior systemic therapy .\n2. Adequate organ and hematologic function.\n3. At least 1 extracranial measurable lesion.\n4. An ECOG activity status score of 0-1.\n5. A life expectancy of ≥ 3 months.\n6. Eligible participants of childbearing potential (both males and females) must agree to using effective contraception throughout the study period.\n7. Good compliance and willingness to follow up.\n\nExclusion Criteria:\n\n1. Prior to first dose, received systemic antitumor therapy , scheduled major surgical procedure within 4 weeks , received systemic immunostimulants within 5 half-lives and systemic corticosteroids or other immunosuppressive medications within 14 days.\n2. A history of active autoimmune disease within the past 2 years.\n3. A history of clinically significant cardiovascular disease, severe cardiac rhythm\u002Fconduction abnormalities or LVEF\\\u003C50%. A history of severe pulmonary disease that may lead to severe episodes of dyspnea.\n4. A severe acute or chronic infection when enrollment.\n5. Remaining the toxic reaction in previous anti-tumor therapy that has not recovered to ≤ Grade 1 .\n6. Unresolved \\> grade 1 irAE or the history of a grade ≥ 3 irAE in previous immunotherapy, or known hypersensitivity to the formulation of the investigational product.\n7. Clinically active CNS metastases or meningeal metastases.\n8. A history of other type of malignancies.\n9. Received a live attenuated vaccine within 28 days prior to the administration of the investigational product.\n10. Poor compliance.\n11. A history of alcohol\u002Fdrugs abuse.\n12. Current pregnancy or breastfeeding.\n13. Other severe physical or mental illnesses or abnormal laboratory test results that the investigator deems unsuitable for participation in this study considering safety and compliance.",{"count":696,"type":21},58,[57],"The goal of this clinical trial is to learn about the safety, tolerability and preliminary effectiveness of a treatment for patients with advanced melanoma,regardless of gender, aged between 18 and 75 years (inclusive).\n\nParticipants will receive the investigational product intravenously every two or three weeks. The treatment will continue for a maximum of two years for those who do not show signs of disease progression or experience intolerable side effects.",[29,700],"Advanced Solid Tumor","2025-07-30",{"date":703,"type":36},"2025-08-06",{"date":705,"type":21},"2025-08-08",{"date":70,"type":21},{"name":708,"class":214},"Biotroy Therapeutics",{"id":710,"slug":711,"hasResults":12,"nctId":712,"briefTitle":713,"officialTitle":714,"acronym":715,"eligibilityCriteria":716,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":717,"targetDuration":4,"studyType":22,"phases":719,"briefSummary":720,"conditions":721,"keywords":722,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":730,"lastUpdatePostDateStruct":731,"startDateStruct":733,"completionDateStruct":735,"leadSponsor":737,"locationsCount":4},"100596052","phase-1-assessment-of-safety-and-efficacy-of-opm-101-combined-with-anti-pd-1-in-patients-with-advanced-melanoma-showing-resistance-to-anti-pd-1-100596052","NCT07040436","Assessment of Safety and Efficacy of OPM-101 Combined With Anti-PD-1 in Patients With Advanced Melanoma Showing Resistance to Anti-PD-1","REVERT Study: A Phase 1b\u002F2a Study to Assess the Safety and Efficacy of OPM-101 Combined With Anti-PD-1 in Patients With Advanced Melanoma Showing Resistance to Anti-PD-1","REVERT","Inclusion criteria\n\n1. Written informed consent provided prior to any study-related procedure.\n2. Histologically confirmed, unresectable or metastatic stage III or IV melanoma.\n3. At least one measurable lesion per RECIST v.1.1 criteria.\n4. Patients with a documented and confirmed Progressive Disease with an anti-PD-1-based treatment given alone or in combination (except combination with an anti-LAG-3 drug). Progressive disease will be determined by the PI based on the SITC v3.0 guidelines.\n\n   Note: Patients who have been treated with a combination of nivolumab and ipilimumab will also be considered for study inclusion.\n5. Patients with no anti-PD-1-based treatment administration within 4 weeks (or 6 weeks for a treatment with pembrolizumab administered with a 400 mg q6w scheme) prior to study treatment initiation.\n6. Patients accepting to undergo a fresh biopsy at baseline and after 12 weeks of treatment (for Phase 1b only).\n\n   * In case a fresh baseline biopsy collection would represent a medical risk for the patient, an archival biopsy could be used, after discussion with the Medical Monitor and the Principal Investigator (PI)\n   * If archival sample is unavailable, and the patient cannot provide a fresh tumour biopsy at baseline due to medical risk or inaccessibility, the patient may still be enrolled if agreed upon between the Investigator and the Sponsor.\n7. Male or female patients ≥18 years.\n8. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.\n9. Estimated life expectancy ≥3 months.\n10. Adequate hematologic parameters and organ function defined by:\n\n    * white blood cell count ≥3,000\u002FµL\n    * absolute neutrophil count ≥1,500\u002FµL without support of filgrastim\n    * platelet count ≥75,000\u002FµL\n    * haemoglobin (Hgb) ≥9 g\u002FdL (criterion must be met without erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks)\n    * calculated creatinine clearance ≥50 mL\u002Fmin (Cockroft Gault formula)\n    * serum total bilirubin ≤1.5 x ULN (or ≤3.0 x ULN if documented Gilbert syndrome) analysed using vanadate method.\n    * AST and ALT ≤2.5 x ULN (or ≤5.0 x ULN if liver metastases)\n    * International normalized ratio (INR) ≤1.5 x ULN unless patient is receiving anticoagulant therapy if partial thromboplastin or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants\n    * Urinalysis negative for haematuria\n11. Females of childbearing potential must have confirmed negative pregnancy test prior to OPM-101 administration (daily oral dosing) and willing to use effective contraception during OPM-101 treatment and for at least 3 months after the last dose of OPM-101. Females considered of non-childbearing potential are post-menopausal women and women having undergone hysterectomy.\n12. Females with childbearing potential must not be breast feeding.\n13. Males must agree to use effective barrier contraception during OPM-101 treatment and for 90 days (a spermatogenesis cycle) after the last dose of OPM-101.\n\nExclusion criteria\n\n1. Diagnosis of primary uveal and\u002For ocular melanoma, as well as mucosal melanoma\n2. Active leptomeningeal disease or uncontrolled brain metastasis. Patients with equivocal findings or with confirmed brain metastases are eligible for enrolment provided they are asymptomatic without the need for corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s).\n3. Patients who have received any line of therapy with a BRAF inhibitor or MEK inhibitor in the advanced disease setting.\n4. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:\n\n   * 4 weeks for any anti-PD-1-based therapy (except for previous treatments with pembrolizumab administered with a 400 mg q6w scheme for which the duration should be 6 weeks)\n   * 4 weeks for radiation therapy\n   * 2 weeks for limited field radiation for palliation\n   * 4 weeks or 5 half-lives (whichever is longer) for continuous or intermittent small molecule therapeutics or any other investigational agent, receiving study therapy or has participated in a study of an investigational agent and received study therapy, or used an investigational device. The participation in the follow-up Phase (i.e., receiving no study treatment) of a prior study is allowed.\n   * 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosoureas and mitomycin C\n5. History of severe or life-threatening immune-related (IR) AEs during a previous treatment with anti-PD-1\n\n   * IR-myocarditis\n   * Grade ≥3, IR- interstitial lung disease IR-renal toxicity.\n   * Grade 4 for IR-maculopapular rash, IR-diarrhoea and enterocolitis, IR-rheumatological toxicity, IR-neuro(muscular) toxicity, IR-hepatotoxicity\n6. Unrecovered CTCAE at time of screening\n\n   * Any patient unrecovered to a CTCAE grade ≤2 for patients who has been pre-treated with anti-PD-1 monotherapy\n   * Any patient unrecovered to a CTCAE grade ≤ 1 for patients who has been pre-treated with the combination of nivolumab plus ipilimumab\n7. Any of the following cardiovascular criteria:\n\n   * Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤28 days before the first dose of study drug(s)\n   * Symptomatic pulmonary embolism ≤28 days before the first dose of study drug(s)\n   * Any history of acute myocardial infarction ≤6 months before the first dose of study drug(s)\n   * Any history of heart failure meeting New York Heart Association Classification (NYHA) class III or IV ≤6 months before the first dose of study drug(s)\n   * Any event of ventricular arrhythmia ≥Grade 2 in severity ≤6 months before the first dose of study drug(s)\n   * Any history of cerebrovascular accident ≤6 months before the first dose of study drug(s)\n   * Uncontrolled hypertension: systolic pressure ≥160 mmHg or diastolic pressure ≥100 mmHg despite anti-hypertension medications ≤28 days before the first dose of study drug(s)\n   * Any episode of syncope or seizure ≤28 days before the first dose of study drug(s)\n8. Any condition that required systemic treatment with either corticosteroids (\\>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤4 weeks before administration of study drug.\n\n   Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded:\n   * Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent)\n   * Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption\n   * Short course (≤7 days) of corticosteroid prescribed prophylactically, e.g., for contrast dye allergy, or for the treatment of a non-autoimmune condition, e.g., delayed-type hypersensitivity reaction caused by contact allergen\n9. Active infection requiring systemic therapy\n10. History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years\n11. Active autoimmune diseases or history of autoimmune diseases that may relapse. Patients with the following diseases are not excluded and may proceed to further screening:\n\n    * Controlled type 1 diabetes\n    * Hypothyroidism provided it is managed with hormone replacement therapy only\n    * Controlled celiac disease\n    * Skin diseases not requiring systemic treatment, e.g., vitiligo, psoriasis, alopecia\n    * Any other disease that is not expected to recur in the absence of external triggering factors\n12. Known history of Human Immunodeficiency Virus (HIV, HIV 1\u002F2 antibodies), known active Hepatitis B, i.e., HBsAg positive or detectable HBV DNA, known active Hepatitis C, i.e., detectable HCV RNA (qualitative).\n13. Hypersensitivity to any excipients in OPM-101 formulation, i.e., lactose, cellulose, polyvinylpyrrolidone, magnesium stearate.\n14. Hypersensitivity to any excipients in the pembrolizumab formulation (L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80)\n15. Patients who received live vaccine within 30 days of planned start of the study therapy.\n16. History or current evidence of any condition, therapy, laboratory abnormality or psychiatric or substance abuse disorder that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.\n17. Patients who received homeopathy within 14 days of planned start of the study therapy.",{"count":718,"type":21},41,[57,203],"This is a phase 1b\u002F2a study including a dose escalation part (Phase 1b) and an extension part (Phase 2a).\n\nBoth parts will be open-label, multicenter study of OPM-101 combined with the anti-PD-1 pembrolizumab as per standard of care in patients with MM who have been receiving an anti-PD-1-based treatment and have shown resistance to it, as defined by the Society for Immunotherapy of Cancer (SITC) criteria (Kluger, 2020). The objective of the study is to assess whether the addition of OPM-101 will resensitisze the tumour to the anti-PD-1-based treatment.\n\nPotential patients will be screened for this study during the period between initial evidence of disease progression on anti-PD-1 treatment and the required radiographic confirmation of disease progression. The intent is to initiate treatment with OPM-101 once the suspicion of disease progression on anti-PD-1-based therapy is confirmed, and the patient has signed the study Information and Consent Form. No anti-PD-1-based treatment should be administered within 4 weeks prior to study treatment initiation.\n\nIn the dose escalation part (Phase 1b) of the study, two different doses of OPM-101 will be evaluated (75 mg bid and 150 mg bid) in combination with pembrolizumab. Patients will receive the dose and regimen of pembrolizumab, as per the authorised product SmPC, in sequential cohorts using a 3 + 3 design, escalating if 0 of 3 (or 1 of 6) patients experience a dose-limiting toxicity (DLT) during the first 6 weeks of treatment and not escalating if 2 of 6 patients experience a DLT.\n\nThe RP2D of OPM-101 for the second part of the study (Phase 2a) in combination with pembrolizumab will be based on the rate of DLTs, incidence and severity of Treatment-Related AEs (AEs) and SAEs, and frequency of dose holds, reductions and discontinuations.\n\nA Data and Safety Monitoring Board (DSMB) will assess the safety criteria and make recommendations about dose escalation\u002Fde-escalation during the Phase 1b part, and on the RP2D to be used for further patients in the Phase 2a. The selection of the dose level for the Phase 2a will be based on safety and on preliminary PK\u002FPD or even trends of efficacy. The DSMB will also review periodically the data during the Phase 2a and make recommendations about the continuation of the study.\n\nThe cohort expansion part (Phase 2a) of the study will be conducted once the Phase 1b is completed and a safe and tolerated dose (potentially 150 mg bid) has been determined. Patients will receive daily oral treatment with OPM-101, while taking pembrolizumab for at least 12 weeks, i.e., at the time of the radiographic assessment of the disease for the primary endpoint evaluation. Patients who show a treatment response with Disease Control (CR, PR or SD) at 12 weeks will continue treatment with \\[OPM-101 + pembrolizumab\\] up to 24 weeks, when the second radiographic disease assessment is performed.",[29],[723,31,724,488,725,726,727,728,729],"OPM-101","resistance","RIPK2","advanced","immuno-oncology","anti-PD1 refractory","pembrolizumab","2025-06-24",{"date":732,"type":36},"2025-06-27",{"date":734,"type":21},"2025-09",{"date":736,"type":21},"2027-12",{"name":738,"class":214},"Oncodesign Precision Medicine"]