IDEAYA and Servier report Phase 2/3 OptimUM-02 results showing darovasertib plus crizotinib significantly improved PFS and response rates in first-line HLA-A*A2:01-negative metastatic uveal melanoma, supporting planned FDA NDA filing.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
IDEAYA Biosciences and Servier reported positive topline results from the Phase 2/3 registrational OptimUM-02 trial (NCT05987332) evaluating darovasertib plus crizotinib in first-line HLA-A*A2:01-negative metastatic uveal melanoma (mUM). The study met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) versus investigator’s choice of therapy (ICT), with overall response rate (ORR) and duration of response (DOR) assessed as secondary endpoints.
The global randomized study enrolled 313 patients, with 210 receiving the darovasertib combination and 103 treated with ICT, primarily ipilimumab plus nivolumab or pembrolizumab. Patients receiving the combination experienced a 58% reduction in risk of disease progression (HR 0.42; p<0.0001), with median PFS of 6.9 months compared with 3.1 months in the ICT arm. ORR reached 37.1% versus 5.8%, including five complete responses in the combination arm and none in the control group. Median duration of response was 6.8 months, while overall survival data remain immature with an early favorable trend.
The regimen was generally well tolerated, with a manageable safety profile consistent with prior experience. The most common grade 3 or higher treatment-emergent adverse events included diarrhea, syncope, and hypotension, and treatment-related serious adverse events occurred in the single-digit percent range.
IDEAYA CEO Yujiro S. Hata said the randomized study showed clinically meaningful improvements in PFS and response rates that could provide a new treatment option for first-line metastatic uveal melanoma.
Servier R&D Executive Vice President Claude Bertrand described the findings as an encouraging milestone supporting development of a potential first-in-class therapy.
Investigator Dr. Meredith McKean highlighted the high unmet need and lack of approved therapies for HLA-A*A2:01-negative patients.
Based on these results, IDEAYA plans to submit a New Drug Application to the U.S. FDA in the second half of 2026, with additional data from OptimUM-02 expected at a major medical conference later this year.
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About the Writer
Sana Jamil Khan is a B.Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.