The OptimUM-02 trial shows that the oral combination of darovasertib and crizotinib significantly improves outcomes for patients with a difficult-to-treat form of eye cancer, metastatic uveal melanoma that is HLA-A*02:01–negative.
The treatment doubled median progression-free survival to 6.9 months compared to 3.1 months with standard therapies. It also reduced the risk of disease progression or death by 58% and achieved a 37.1% response rate, compared to 5.8% with usual care. Five patients even reached complete remission.
Uveal melanoma is an aggressive cancer that often spreads to the liver, and many patients have no approved treatment options. Darovasertib blocks the PKC pathway driving tumor growth, while crizotinib targets the cMET pathway involved in spread. The all-oral combination was generally well tolerated, with side effects such as diarrhea and low blood pressure. A regulatory filing is planned for 2026, and further studies are exploring earlier-stage use.