IDEAYA Biosciences, a precision medicine oncology company, and Servier, an independent international pharmaceutical group governed by a foundation, have announced positive topline results from their phase 2/3 registrational trial, OptimUM-02, evaluating darovasertib in combination with crizotinib (darovasertib combination) in patients with first-line (1L) HLA-A*A2:01-negative metastatic uveal melanoma (mUM).
The darovasertib combination met the trial’s primary endpoint of a statistically significant improvement in median progression-free survival (PFS) relative to the investigator choice of therapy (ICT) arm as assessed by blinded independent central review (BICR). The secondary endpoints in the study include overall response rate (ORR) and duration of response (DOR).
‘Metastatic uveal melanoma is an area of high unmet medical need with poor prognosis and short overall survival, and there are currently no approved therapies for HLA-A 02:01-negative mUM patients.
‘The data from the OptimUM-02 study provides potential practice changing results for the treatment of first-line metastatic uveal melanoma,’ said Dr Meredith McKean, Sarah Cannon Research Institute.
OptimUM-02 study highlights
OptimUM-02 is a global, randomised phase 2/3 trial in 1L HLA-A A2:01-negative MUM evaluating darovasertib combination arm of 210 patients versus the ICT arm reflective of real-world clinical practice that consists of 103 patients.
The ICT arm was composed of 76% (n=78) ipilimumab plus nivolumab (anti-CTLA-4/PD-1) and 24% (n=25) pembrolizumab (anti-PD-1).
The primary endpoint is median PFS as assessed by BICR, which will be used to support an initial NDA submission in the United States. Topline results were from a total of 313 patients enrolled in the Phase 2b/3 portion of the trial as of the cut-off date of January 23, 2026. The PFS analysis was based on a total of 159 events.
Patients treated with the darovasertib combination reduced their risk of disease progression as assessed by BICR by 58% (Hazard Ratio of 0.42; 95% CI: 0.30, 0.59; p-value: <0.0001) and achieved a statistically significant improvement in median PFS of 6.9 months versus 3.1 months in the ICT arm.
The overall response rate (ORR) by BICR in the darovasertib combination and ICT arm was 37.1% and 5.8% (p-value: <0.0001), respectively. There were five complete responses by BICR observed in the darovasertib combination arm, and no complete responses observed in the ICT arm. The median duration of response (DOR) in the darovasertib combination arm was 6.8 months.
The overall survival (OS) data is not mature. However, in the OptimUM-02 study, there is an early trend in improvement in OS with the darovasertib combination arm versus the ICT arm.
Darovasertib combination was generally well-tolerated with a manageable safety profile consistent with prior reported results and known side-effects of each drug. The most common Grade 3+ treatment emergent adverse events included diarrhea, syncope, and hypotension. The treatment-related serious adverse events rate in the darovasertib combination was in the single-digit percent range.
Based on these data, the company will target to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second half of 2026. IDEAYA plans to provide additional details from OptimUM-02 at a major medical conference in 2026.
