🚨 Landmark result (August 19, 2026): Merck and Moderna announced that the Phase 3 INTerpath-001 trial of intismeran autogene (V940 / mRNA-4157) — a personalized neoantigen mRNA cancer vaccine — plus KEYTRUDA (pembrolizumab) met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS) in patients with completely resected high-risk Stage IIB–IV melanoma — the first mRNA cancer vaccine to succeed in a Phase 3 trial. It remains investigational (no FDA approval yet; a regulatory filing is the expected next step, and full data will be presented at an upcoming medical meeting). INTerpath-001 itself (adjuvant, resected) is no longer recruiting, but a related recruiting option for advanced / unresectable / metastatic melanoma is the Phase 2 INTerpath-012 (NCT06961006: first-line V940 + pembrolizumab). Full details on the intismeran (V940) drug page.
Treatment duration / de-escalation — intermittent vs continuous PD-1 in long responders
Standard of care: Checkpoint immunotherapy (nivolumab ± ipilimumab) for most patients. BRAF/MEK inhibitors (dabrafenib + trametinib, encorafenib + binimetinib) for BRAF V600-mutant melanoma. Immunotherapy first, targeted therapy second — even for BRAF-mutant patients.
Recruiting Trials by Treatment Setting
Neoadjuvant / Perioperative (Stage III Resectable)
Immunotherapy before and/or after surgery — a rapidly evolving area with practice-changing results. Intratumoral neoadjuvant approaches are now also in Phase 3:
Immunotherapy combinations:
NCT06794775 - SWE-NEO: Monotherapy vs combined immunotherapy in resectable melanoma (Phase 3)
NCT05770102 - DETERMINE: Atezolizumab in adult and pediatric melanoma (Phase 3)
Checkpoint immunotherapy is standard first-line. Trials test new combinations, novel agents, and the first PRAME-targeting head-to-head vs the anti-PD-1 standard:
PRAME bispecific (new 1L target class):
NCT06112314 - PRISM-MEL: IMC-F106C (brenetafusp, PRAME × CD3 bispecific) regimen vs nivolumab regimens in previously untreated advanced melanoma (Phase 3, the first PRAME bispecific to challenge anti-PD-1 in 1L)
NRAS-mutant melanoma (biomarker-targeted):
NCT06008106 - Tunlametinib (MEK inhibitor) vs combination chemotherapy in advanced NRAS-mutant melanoma (Phase 3, the first dedicated NRAS-mutant Phase 3 — NRAS is the second-most-common driver in melanoma after BRAF, ~15-20%)
Treatment duration / de-escalation (for patients in response):
NCT02821013 - Intermittent vs continuous anti-PD-1 in metastatic melanoma (Phase 3 randomized duration trial)
Advanced / Metastatic — After Prior Immunotherapy
Options after checkpoint failure — TIL therapy, bispecifics, oncolytic virus, TCR-T, and novel mechanisms:
Bispecific antibodies (post-IO):
NCT05549297 - Tebentafusp (TEBE-AM) vs investigator's choice in previously treated advanced cutaneous melanoma, HLA-A*02:01+ (Phase 3). Cross-cancer extension of the FDA-approved HLA-A*02:01+ metastatic uveal melanoma indication into the much larger cutaneous melanoma post-IO population — gp100 is a melanocyte differentiation antigen expressed in both uveal and cutaneous melanoma, so the same ImmTAC gp100/HLA-A*02:01 mechanism applies.
NCT05868707 - OH2 oncolytic virus injection in melanoma (Phase 3)
Post-PD-1/CTLA-4 combinations:
NCT06264180 - VO + nivolumab vs physician's choice in advanced melanoma that progressed on both anti-PD-1 and anti-CTLA-4 (Phase 3, addresses the highest-unmet-need post-IO setting)
Novel combinations:
NCT06624644 - LNS8801 ± pembrolizumab in refractory melanoma (Phase 3)
CNS involvement changes treatment strategy. Trials test whether stereotactic radiosurgery (SRS) adds to systemic therapy and which SRS fractionation schedule is optimal:
NCT05522660 - Systemic therapy ± SRS for asymptomatic brain mets from melanoma or NSCLC (Phase 3)
NCT06500455 - Fractionated SRS (3 treatments) vs single-fraction SRS for intact brain mets, any solid tumor (Phase 3)
How do I find melanoma clinical trials I'm eligible for?
Enter your melanoma details into ClinTrialFinder — including BRAF/NRAS mutation status, stage, and prior treatments. The AI matches you with trials based on your specific profile in minutes.
What melanoma trials are currently recruiting?
There are 365 recruiting interventional trials for melanoma in August 2026 including 36 Phase 3 studies. Recent Phase 3 entrants: SUPRAME IMA203 PRAME TCR-T (NCT06743126, Jun 10), PD-1 + anti-LAG-3 combinations (NCT06246916), VO + nivolumab post-anti-PD-1/anti-CTLA-4 (NCT06264180), EIK1001 + pembro 1L (NCT06697301), PD-1 therapy-duration de-escalation NCT02821013. Class anchors: IMC-F106C (brenetafusp, PRAME bispecific) vs nivolumab in 1L (PRISM-MEL NCT06112314), tunlametinib MEK in NRAS-mutant (NCT06008106), Daromun neoadjuvant intratumoral Stage IIIB/C/D (NCT03567889). Plus checkpoint immunotherapy combinations, BRAF/MEK targeted therapy, TIL cell therapy (lifileucel + pembrolizumab), oncolytic virus therapy, brain-metastases SRS combinations.
Find Melanoma Trials Matched to Your Situation
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This page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here.
