Clinical Trials for Melanoma

A Randomized Phase 2 Trial of Ipilumumab and Nivolumab With or Without Hypofractionated Radiotherapy in Patients With Metastatic Melanoma

Moderate burden on patient

The trial has a moderate burden on patients. An example would be a trial testing an IV drug, with scans every 8 weeks which would be more frequent than standard of care.

Started >3 years ago

The trial was activated more than 3 years ago. This is not always bad but can indicate that the trial has less current treatments, or has had trouble getting enough patients to enroll due to other issues.

HealthScout AI summary: Adults with metastatic melanoma (ECOG 0–1) with at least two measurable lesions and one lesion amenable to hypofractionated radiotherapy are randomized to receive standard ipilimumab (anti–CTLA-4) plus nivolumab (anti–PD-1) with or without HFRT (8 Gy × 3 to a single lesion). Excludes active CNS disease requiring urgent therapy, prior checkpoint inhibitors in the metastatic setting, significant autoimmune disease/immunosuppression, active infections, or HFRT contraindications.

ClinicalTrials.gov ID: NCT03646617

Phase II Study of Binimetinib With Encorafenib in Patients With Metastatic Melanoma and CNS Metastases

Moderate burden on patient

The trial has a moderate burden on patients. An example would be a trial testing an IV drug, with scans every 8 weeks which would be more frequent than standard of care.

Started >3 years ago

The trial was activated more than 3 years ago. This is not always bad but can indicate that the trial has less current treatments, or has had trouble getting enough patients to enroll due to other issues.

HealthScout AI summary: Adults with BRAFV600-mutant metastatic melanoma with active CNS involvement (parenchymal and/or leptomeningeal) receive high-dose encorafenib (BRAF inhibitor) plus binimetinib (MEK1/2 inhibitor); includes two cohorts: prior BRAF/MEK–treated with progressive CNS disease and BRAF/MEK–naive, with prior immunotherapy allowed. Aims to evaluate intracranial disease control and PFS with continuous oral therapy; key exclusions include significant cardiovascular disease, recent thromboembolism, and strong CYP3A modulators.

ClinicalTrials.gov ID: NCT05026983

Phase 2 Study of Axitinib + PD-1 Blockade in Mucosal Melanoma With Pilot Addition of Stereotactic Body Radiotherapy or Ipilimumab in Select Progressors

Moderate burden on patient

The trial has a moderate burden on patients. An example would be a trial testing an IV drug, with scans every 8 weeks which would be more frequent than standard of care.

Started >3 years ago

The trial was activated more than 3 years ago. This is not always bad but can indicate that the trial has less current treatments, or has had trouble getting enough patients to enroll due to other issues.

HealthScout AI summary: Adults with unresectable or metastatic mucosal melanoma (head/neck including conjunctival, GI, or GU), treatment-naive, ECOG 0–2, including selected patients with brain metastases, receive nivolumab (PD-1 inhibitor) plus axitinib (VEGFR1–3 TKI); at progression, patients may continue doublet with SBRT for oligoprogression or add ipilimumab (CTLA-4 inhibitor) for multifocal/non-SBRT-amenable progression. Primary endpoint is objective response by RECIST 1.1 within 1 year.

ClinicalTrials.gov ID: NCT05384496

Phase 1/2 Study of an EZH2 Inhibitor (Tazemetostat) in Combination With Dual BRAF/MEK Inhibition in Patients With BRAF- Mutated Metastatic Melanoma Who Progressed on Prior BRAF/MEK Inhibitor Therapy

Moderate burden on patient

The trial has a moderate burden on patients. An example would be a trial testing an IV drug, with scans every 8 weeks which would be more frequent than standard of care.

Started >3 years ago

The trial was activated more than 3 years ago. This is not always bad but can indicate that the trial has less current treatments, or has had trouble getting enough patients to enroll due to other issues.

HealthScout AI summary: Adults with BRAFV600E/K metastatic melanoma that progressed on prior BRAF/MEK therapy (and received or are ineligible/intolerant to anti–PD-1) receive tazemetostat, a selective EZH2 (PRC2) inhibitor, alone versus in combination with dabrafenib plus trametinib; phase 2 requires an EZH2 alteration and allows stable CNS metastases. The study tests whether adding EZH2 inhibition to renewed BRAF/MEK blockade overcomes resistance and improves PFS, with crossover permitted at progression.

ClinicalTrials.gov ID: NCT04557956

A Phase II Study of Biomarker Driven Early Discontinuation of Anti-PD-1 Therapy in Patients With Advanced Melanoma (PET-Stop)

Moderate burden on patient

The trial has a moderate burden on patients. An example would be a trial testing an IV drug, with scans every 8 weeks which would be more frequent than standard of care.

Started >3 years ago

The trial was activated more than 3 years ago. This is not always bad but can indicate that the trial has less current treatments, or has had trouble getting enough patients to enroll due to other issues.

HealthScout AI summary: Adults with unresectable stage IIIB–IV cutaneous, acral, mucosal, or unknown-primary melanoma (no ocular or brain mets) who have disease control after ~12 months of standard anti–PD-1 therapy (nivolumab or pembrolizumab, with or without prior ipilimumab) undergo FDG-PET/CT ± biopsy to guide stopping vs continuing PD-1 blockade. Patients with negative imaging/biopsy stop therapy; those with positive imaging and positive/unobtainable biopsy continue anti–PD-1 for another ~12 months.

ClinicalTrials.gov ID: NCT04462406

A Phase II Study of Concurrent Stereotactic Body Radiotherapy With Relatlimab and Nivolumab in Patients With Metastatic Uveal Melanoma

Moderate burden on patient

The trial has a moderate burden on patients. An example would be a trial testing an IV drug, with scans every 8 weeks which would be more frequent than standard of care.

Started >3 years ago

The trial was activated more than 3 years ago. This is not always bad but can indicate that the trial has less current treatments, or has had trouble getting enough patients to enroll due to other issues.

HealthScout AI summary: Adults with measurable metastatic uveal melanoma (ECOG 0–1), including those previously treated with anti–PD-1 or tebentafusp but not prior LAG-3 therapy, receive concurrent SBRT to 1–5 metastases plus Opdualag (nivolumab anti–PD-1 + relatlimab anti–LAG-3) every 4 weeks. Excludes active CNS mets, heavy liver burden (>50%), prior liver radiation/embolization, active hepatitis B, significant autoimmune disease, or systemic steroids.

ClinicalTrials.gov ID: NCT05077280

A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy

Moderate burden on patient

The trial has a moderate burden on patients. An example would be a trial testing an IV drug, with scans every 8 weeks which would be more frequent than standard of care.

Started >3 years ago

The trial was activated more than 3 years ago. This is not always bad but can indicate that the trial has less current treatments, or has had trouble getting enough patients to enroll due to other issues.

HealthScout AI summary: Adults with untreated metastatic cutaneous melanoma starting standard PD-1 monotherapy or PD-1 plus CTLA-4 receive a single booster of tetanus-diphtheria or inactivated polio vaccine given near the largest tumor at cycle 4 to trigger immune recall and potentially enhance checkpoint efficacy. Excludes uveal/mucosal melanoma and significant immunosuppression; requires biopsy-amenable lesion and adequate counts.

ClinicalTrials.gov ID: NCT05077137

Phase 1 Dose Escalation and Expansion Study of PRAME T Cell Receptor (TCR) Engineered NK Cells in Participants With Recurrent and/or Refractory Melanoma (PRAMETIME-Mel)

High burden on patient

The trial has a high burden on patients. An example would be a phase 1 trial with extra tumor biopsies and frequent pharmacokinetic blood draws.

HealthScout AI summary: Adults with unresectable/metastatic melanoma that is relapsed/refractory to prior PD-1–based checkpoint therapy (HLA-A*02:01 positive, ECOG 0–1) receive lymphodepleting cyclophosphamide/fludarabine followed by a single infusion of PRAME-TCR-NK cells. PRAME-TCR-NK is an allogeneic NK cell product engineered with a TCR targeting PRAME presented by HLA-A*02:01 to enhance antigen-specific cytotoxicity; uveal melanoma may be enrolled in expansion.

ClinicalTrials.gov ID: NCT06660420

A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma

Moderate burden on patient

The trial has a moderate burden on patients. An example would be a trial testing an IV drug, with scans every 8 weeks which would be more frequent than standard of care.

No known activity

No investigational drug(s) in this trial have shown anticancer activity yet in clinical trials

HealthScout AI summary: Adults with unresectable stage III/IV cutaneous melanoma that progressed during or within 6 months of prior anti–PD‑1/PD‑L1 therapy receive dapansutrile (OLT1177), an oral NLRP3 inflammasome inhibitor blocking caspase‑1–mediated IL‑1β/IL‑18 maturation, with pembrolizumab 200 mg IV q3w after a 14‑day dapansutrile lead-in. Excludes ocular/mucosal melanoma, active CNS disease (unless treated/stable), significant autoimmune disease, and active infections; ECOG 0–2 required.

ClinicalTrials.gov ID: NCT04971499

Randomized Phase II Study of Pembrolizumab/Lenvatinib With and Without Healthy Donor FMT (hdFMT) in Relapsed/Refractory (R/R) Melanoma

High burden on patient

The trial has a high burden on patients. An example would be a phase 1 trial with extra tumor biopsies and frequent pharmacokinetic blood draws.

HealthScout AI summary: Adults with cutaneous or unknown-primary melanoma that has progressed on prior anti–PD-1/PD-L1 (including post-adjuvant) are randomized to pembrolizumab (anti–PD-1) plus lenvatinib (multikinase inhibitor of VEGFR/FGFR/PDGFR/RET/KIT) with or without healthy-donor fecal microbiota transplant delivered by endoscopy or oral capsules. Key exclusions include uveal/mucosal/acral melanoma, prior anti-angiogenic therapy or microbiome-directed therapy, active autoimmune disease requiring systemic treatment, and contraindications to FMT; treated, stable brain metastases are allowed.

ClinicalTrials.gov ID: NCT06030037