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

Last updated: May 31, 2026

Current Clinical Trial Landscape

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.

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)
• NCT06007690 - CoMpass: belzupacap sarotalocan (AU-011) vs sham control in indeterminate choroidal lesions or small choroidal melanoma (Phase 3, Aura Biosciences). First non-radiation, non-enucleation Phase 3 for small primary uveal melanoma — photodynamic therapy.

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).
• NCT03467516 - TIL (tumor-infiltrating lymphocytes) therapy
• 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 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 - SCANDIUM-III: PHP + checkpoint inhibitors (Phase 3)
• NCT07276386 - Melphalan/PHP + tebentafusp combination

Showing selected notable trials. View all 29 recruiting interventional trials on ClinicalTrials.gov (corpus count, May 2026).

Frequently Asked Questions