Results from the Phase 3 OptimUM-02 trial show that the combination of darovasertib and crizotinib significantly improves outcomes for patients with HLA-A*02:01–negative metastatic uveal melanoma, a rare and aggressive form of eye cancer with no approved treatment options for this population.
The targeted therapy works by blocking the PKC signaling pathway, which is activated in more than 95% of uveal melanoma tumors. Patients receiving the combination achieved a median progression-free survival of 6.9 months, compared with 3.1 months for those treated with investigator-selected standard therapies, reducing the risk of disease progression or death by 58%.
The treatment also produced substantially higher tumor response rates, with 37.1% of patients experiencing tumor shrinkage compared with 5.8% in the control group.
The combination demonstrated a favorable safety profile, with treatment-related serious adverse events occurring in 9.2% of patients versus 25.0% in the standard-care group. The most common side effects included diarrhea, nausea, and peripheral edema, which were generally manageable.