34 Uveal Melanoma Clinical Trials Recruiting Now (September 2026): Tebentafusp, Darovasertib, CoMpass AU-011, RP2 Oncolytic, TIL, PHP Liver-Directed, ATOM, AMUM, SCANDIUM-III

Last updated: September 13, 2026

Answer a few questions to find clinical trials matched to your specific Uveal Melanoma situation.

A thorough search takes ~15 minutes — we'll email your results. No sign-up.

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.

Know your HLA type and genetic markers? Get matched to uveal melanoma trials in minutes.

Find Matching Trials

Recruiting Trials by Treatment Setting

Localized / Primary Tumor (Neoadjuvant + Primary-Tumor Therapy)

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

NCT06414590 - Neoadjuvant tebentafusp before primary treatment
NCT07015190 - Neoadjuvant darovasertib (PKC inhibitor) in primary uveal melanoma (Phase 3, IDEAYA)

First-Line Metastatic

For previously untreated metastatic uveal melanoma — patient must be ICI-naïve for several of these:

NCT06519266 - SCANDIUM-III: PHP + ipilimumab/nivolumab vs ipilimumab/nivolumab alone (Phase 3)
NCT06581406 - RP2 (HSV-1 oncolytic immunotherapy) + nivolumab vs ipilimumab + nivolumab in immune-checkpoint-inhibitor-naïve metastatic uveal melanoma (Phase 2/3, Replimune). First oncolytic immunotherapy combination Phase 2/3 in 1L metastatic uveal melanoma.
NCT06121180 - Cemiplimab + ziv-aflibercept

Second-Line / Refractory

After progression on first-line therapy:

NCT03686124 - ACTengine: IMA203 PRAME-targeted TCR-T cell therapy ± nivolumab (Immatics; broad PRAME-expressing solid-tumor basket per trial registration; uveal melanoma is a known PRAME-high indication and uveal cohorts have been reported in sponsor presentations — verify uveal cohort enrollment is open with the sponsor before considering).
NCT05607095 - LN-144/LN-145 TIL therapy
NCT07136181 - NBM-BMX-UM: NBM-BMX novel agent (Novelwise Pharmaceutical, Phase 1/2)

Adjuvant (High-Risk After Primary Treatment)

NCT06246149 - ATOM: Adjuvant tebentafusp in high-risk ocular/uveal melanoma (Phase 3, EORTC)
NCT06932757 - Adjuvant quisinostat (HDAC inhibitor) in high-risk uveal melanoma (Phase 2)
NCT05502900 - AMUM: Adjuvant melatonin for medium/large-size posterior uveal melanoma (Phase 3, single-PI academic trial, n=100). Tests whether melatonin after primary tumor diagnosis can prevent or delay metastases.

Trials by Treatment Approach

Tebentafusp / Bispecific T-Cell Engagers (9 trials)

Tebentafusp (Kimmtrak) is a bispecific gp100-CD3 T-cell engager on the ImmTAC TCR-mimetic platform (Immunocore) — FDA-approved Jan 2022 as the only therapy for HLA-A*02:01+ metastatic uveal melanoma. Trials explore earlier-setting (ATOM adjuvant, neoadjuvant, 1L treatment-naive), liver-directed combinations (PHP, radioembolization), T cell persistence combinations (IL-2, roginolisib), and cross-cancer extensions (TEBE-AM cutaneous melanoma Phase 3, clear cell sarcoma Phase 2 NCT06942442 — the first non-melanoma ImmTAC). See the Tebentafusp drug page for the full ImmTAC platform mechanism, HLA-A*02:01 eligibility, CRS safety profile, and trial-by-trial detail. 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.

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 - SCANDIUM-III: PHP + checkpoint inhibitors (Phase 3)
NCT07276386 - Melphalan/PHP + tebentafusp combination

Showing selected notable trials. View all 34 recruiting interventional trials on ClinicalTrials.gov (corpus count, September 2026).

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 34 recruiting interventional trials for uveal melanoma in September 2026 including 6 Phase 3 studies. Recent Phase 3: neoadjuvant darovasertib in primary uveal melanoma NCT07015190. Active classes: tebentafusp combinations (neoadjuvant + adjuvant), PRAME-directed TCR-T cell therapy, TIL therapy, checkpoint immunotherapy with liver-directed PHP, PKC inhibitors (darovasertib), photodynamic therapy for primary tumor (CoMpass AU-011), oncolytic immunotherapy combinations (RP2 + nivo), 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

Enter your HLA status, genetic markers, and treatment history to get AI-matched trial results in minutes.