IDEAYA Biosciences (NASDAQ:IDYA) and Servier reported breakthrough topline results today from the Phase 2/3 OptimUM-02 trial, demonstrating that the combination of darovasertib and crizotinib significantly improved outcomes for patients with first-line HLA-A*02:01-negative metastatic uveal melanoma (MUM).
The data establishes the combination as a potential new standard of care for a patient population with historically limited treatment options.
The registrational trial reached its primary endpoint with high statistical significance.
Patients treated with the darovasertib and crizotinib combination achieved a median progression-free survival (PFS) of 6.9 months, compared to just 3.1 months for those receiving investigator’s choice of chemotherapy.
This represents a 58% reduction in the risk of disease progression or death (HR 0.42; 95% CI 0.30-0.59; p<0.0001).
Beyond the delay in disease progression, the combination showed robust anti-tumor activity.
The confirmed Objective Response Rate (ORR) was 37.1% in the combination arm—including five complete responses—versus a meager 5.8% in the control arm (p<0.0001).
The median duration of response (DOR) was recorded at 6.8 months.
Meanwhile, the safety profile of the combination remained consistent with previous Phase 2 findings.
Most treatment-related adverse events (TRAEs) were Grade 1 or 2, and serious TRAEs occurred in only a single-digit percentage of patients.
The most common side effects included gastrointestinal issues and skin rash, which were managed through standard supportive care and dose adjustments.