Metastatic uveal melanoma: emerging targeted and cellular strategies

In this in-depth video, Prof Sapna Patel discusses several developments in metastatic uveal melanoma presented at ASCO 2026, with a focus on new therapeutic strategies for a rare melanoma subtype with historically poor outcomes and limited systemic treatment options.

The main data concerned OptimUM-02, evaluating first-line darovasertib plus crizotinib in patients with HLA-A*02:01-negative metastatic uveal melanoma.¹ Darovasertib is an oral protein kinase C inhibitor, targeting a pathway activated downstream of the GNAQ/11 alterations that are detected in >95% of uveal melanoma tumours. Crizotinib was added to inhibit MET signalling, a pathway considered relevant in liver-predominant metastatic disease. In the phase IIb analysis, darovasertib plus crizotinib significantly improved progression-free survival (PFS) compared with investigator’s choice, which most consisted of ipilimumab plus nivolumab. Median PFS by blinded independent central review was 6.9 versus 3.1 months, with a hazard ratio of 0.42. The interview also emphasizes the toxicity profile of darovasertib plus crizotinib. Common adverse events included diarrhoea, nausea, peripheral oedema, rash, hypotension and syncope. These toxicities are considered manageable, but they require proactive supportive care, including antiemetics, monitoring of fluid retention and attention to antihypertensive medication.

Two additional approaches were briefly highlighted. Updated data on tumour-infiltrating lymphocyte (TIL) therapy showed durable clinical responses in refractory metastatic uveal melanoma.² In addition, the ongoing REVEAL trial is evaluating intratumoural RP2, an HSV-1-based oncolytic immunotherapy encoding GM-CSF and an anti-CTLA-4-like molecule, combined with nivolumab versus ipilimumab plus nivolumab in immune checkpoint inhibitor-naïve metastatic uveal melanoma.³