343 Melanoma Clinical Trials Recruiting Now (May 2026): Immunotherapy, PRAME Bispecific, BRAF/MEK, TIL, NRAS, Brain Mets

Last updated: May 25, 2026

Current Clinical Trial Landscape

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)
• Intratumoral neoadjuvant:
  • NCT03567889 - NeoDaromun: Daromun (L19IL2 + L19TNF intratumoral) neoadjuvant in clinical Stage IIIB/C/D melanoma (Phase 3)

Advanced / Metastatic — First-Line

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%)
• Next-gen checkpoint combinations:
  • NCT06246916 - Anti-LAG-3 + anti-PD-1 combinations in advanced melanoma (Phase 3)
  • NCT06697301 - EIK1001 + pembrolizumab vs placebo + pembrolizumab first-line (Phase 3)
• 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)
• TIL cell therapy:
  • NCT05727904 - Lifileucel (TIL) + pembrolizumab vs pembrolizumab alone (Phase 3)
• TCR-T cell therapy:
  • NCT06743126 - SUPRAME: IMA203 (PRAME TCR-T) vs investigator's choice (Phase 3)
• Oncolytic virus:
  • 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)
  • NCT03646617 - Ipilimumab + nivolumab ± hypofractionated radiotherapy (Phase 2)

Brain Metastases

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)

Uveal / Ocular Melanoma

Uveal (ocular) melanoma is a biologically distinct disease with its own mutations, treatments, and trial landscape — entirely different from cutaneous melanoma. See our dedicated Uveal Melanoma Clinical Trials page →

Showing selected notable trials. View all 343 recruiting interventional trials on ClinicalTrials.gov.

Frequently Asked Questions