Uveal Melanoma Clinical Trials (April 2026): 37 Recruiting Interventional Studies

Last updated: April 27, 2026

Current Clinical Trial Landscape

Active research areas in 2026:

Tebentafusp (Kimmtrak) combinations and next-generation ImmTAC bispecifics — including 5-year Phase 3 survival data presented at AACR 2026 (16% vs 8% OS rate, doubling survival)
PRAME-directed TCR-T and ImmTAC — brenetafusp (IMC-F106C) entering Phase 3 for melanoma
Checkpoint inhibitor combinations (10 trials) — ipilimumab + nivolumab with liver-directed therapy
TIL (tumor-infiltrating lymphocyte) therapy — including CRISPR-edited TIL
Liver-directed therapies — percutaneous hepatic perfusion (PHP), hepatic artery infusion
PKC inhibitors (darovasertib/IDE196) — targeting the GNAQ/GNA11 signaling pathway

Standard of care: Primary tumor: Plaque brachytherapy or proton beam radiation for most tumors; enucleation for large tumors. Adjuvant: No approved adjuvant therapy — clinical trials are the main option for high-risk patients (BAP1 loss, monosomy 3, Class 2 gene expression). Metastatic (HLA-A*02:01+): Tebentafusp (Kimmtrak) — first FDA-approved therapy for metastatic uveal melanoma. Metastatic (HLA-A*02:01-): No approved targeted therapy; checkpoint immunotherapy (ipi+nivo) used but response rates are low (~15-18%). Liver-directed therapy for liver-dominant disease. Clinical trials are critical for this group.

Understanding Uveal Melanoma

Uveal melanoma is the most common primary eye cancer in adults (~2,500 new cases/year in the US). It behaves very differently from cutaneous (skin) melanoma:

Different driver mutations — GNAQ/GNA11 mutations (not BRAF/NRAS like skin melanoma). This means BRAF inhibitors do NOT work in uveal melanoma.
Liver-predominant metastases — ~90% of metastases go to the liver, making liver-directed therapies especially relevant.
~50% develop metastases — often years after successful treatment of the primary tumor. Median time to metastasis is ~5 years.
Limited immunotherapy response — unlike skin melanoma, uveal melanoma responds poorly to standard checkpoint inhibitors. Tebentafusp (a bispecific T-cell engager) was the breakthrough that changed this.

Key Biomarkers for Trial Eligibility

Several biomarkers determine both prognosis and trial eligibility in uveal melanoma:

HLA-A*02:01 status — the most important biomarker for treatment. Required for tebentafusp (Kimmtrak) and several other ImmTAC trials. About 40-50% of Caucasian patients are HLA-A*02:01 positive. Blood test required.
GNAQ / GNA11 mutation — present in ~85% of uveal melanoma. Activates the PKC/MAPK pathway. Target for darovasertib (PKC inhibitor) and IDE196 trials.
BAP1 loss — present in ~40% of primary tumors. Strongest predictor of metastasis. Patients with BAP1 loss are high-risk and should consider adjuvant trials.
SF3B1 mutation — present in ~15-20%. Associated with late-onset metastases (often >5 years). Better prognosis than BAP1 loss.
EIF1AX mutation — present in ~15-20%. Associated with very low metastatic risk. Generally good prognosis.
Chromosome 3 status — monosomy 3 (loss of one copy) is a strong predictor of metastasis and is closely linked to BAP1 loss.
Gene expression profiling (GEP) — Class 1A (very low risk), Class 1B (low-moderate risk), Class 2 (high risk). Used commercially (DecisionDx-UM) for risk stratification.

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Find Matching Trials

Recruiting Trials by Treatment Setting

Localized / Primary Tumor (Neoadjuvant)

Before or alongside primary treatment (radiation/surgery) for localized disease:

NCT06414590 - Neoadjuvant tebentafusp before primary treatment
NCT07015190 - Neoadjuvant darovasertib (PKC inhibitor) in primary uveal melanoma

First-Line Metastatic

For previously untreated metastatic uveal melanoma:

NCT06519266 - PHP + ipilimumab/nivolumab vs ipilimumab/nivolumab alone
NCT06625516 - Tebentafusp + liver-directed therapy
NCT06121180 - Cemiplimab + ziv-aflibercept

Second-Line / Refractory

After progression on first-line therapy:

NCT03686124 - IMA203 TCR-T cell therapy ± nivolumab
NCT03467516 - TIL (tumor-infiltrating lymphocytes) therapy
NCT05607095 - LN-144/LN-145 TIL therapy
NCT07136181 - NBM-BMX novel agent

Adjuvant (High-Risk After Primary Treatment)

NCT06932757 - Adjuvant quisinostat (HDAC inhibitor) in high-risk uveal melanoma

Trials by Treatment Approach

Tebentafusp / Bispecific T-Cell Engagers (9 trials)

Tebentafusp (Kimmtrak) is a bispecific gp100-CD3 T-cell engager approved for HLA-A*02:01+ metastatic uveal melanoma. Trials explore combinations and next-generation agents. View all →

Checkpoint Inhibitors (10 trials)

PD-1/CTLA-4 inhibitors have limited single-agent activity in uveal melanoma; trials test combinations. View all →

TIL / Cellular Therapy

Tumor-infiltrating lymphocyte (TIL) therapy and TCR-T cells show promise in uveal melanoma.

NCT03467516 - TIL adoptive transfer
NCT04119024 - Gene-modified immune cells

Targeted Therapy (GNAQ/GNA11, PKC)

Most uveal melanomas harbor GNAQ or GNA11 mutations, leading to PKC pathway activation.

NCT03947385 - IDE196 (PKC inhibitor) for GNAQ/GNA11-mutant tumors

Liver-Directed Therapies

Percutaneous hepatic perfusion (PHP) and other liver-directed approaches for liver-predominant metastases.

NCT06519266 - PHP + checkpoint inhibitors
NCT07276386 - Melphalan/PHP + tebentafusp
NCT07501117 - Neoadjuvant immunotherapy for high-risk eye melanoma (Phase 1)

Showing selected notable trials. View all 37 recruiting interventional trials on ClinicalTrials.gov.

Frequently Asked Questions

How do I find uveal melanoma clinical trials I'm eligible for?

Enter your uveal melanoma details into ClinTrialFinder — including HLA-A*02:01 status, GNAQ/GNA11 mutation, BAP1/SF3B1/EIF1AX status, metastatic sites, and prior treatments. The AI matches you with trials based on your specific profile in minutes. No login required.

What uveal melanoma trials are currently recruiting?

There are 37 recruiting interventional trials for uveal melanoma including tebentafusp combinations, PRAME-directed ImmTAC/TCR-T, TIL therapy, checkpoint immunotherapy with liver-directed therapy, PKC inhibitors (darovasertib), and adjuvant trials for high-risk patients.

Why is HLA type important for uveal melanoma treatment?

Tebentafusp (Kimmtrak) — the only FDA-approved therapy for metastatic uveal melanoma — requires HLA-A*02:01 positivity because it targets gp100 peptide presented on HLA-A*02:01 molecules. About 40-50% of Caucasian patients carry this allele. Your HLA type determines whether you're eligible for tebentafusp and several other ImmTAC trials. A simple blood test can determine your HLA status.

What options exist for HLA-A*02:01-negative uveal melanoma patients?

For HLA-A*02:01-negative patients, options include: checkpoint immunotherapy combinations (ipilimumab + nivolumab, ~15-18% response), liver-directed therapy (PHP, hepatic artery infusion) for liver-dominant disease, TIL therapy trials, PRAME-directed TCR-T (if tumor expresses PRAME), and PKC inhibitors for GNAQ/GNA11-mutant tumors. Clinical trials are especially important for this group.

Find Uveal Melanoma Trials Matched to Your Situation

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