Announcement • Jun 02
IDEAYA Biosciences And Servier Present Complete Data From Phase 2/3 OptimUM-02 Trial Of Darovasertib Combination In First Line HLAA2:01 Negative Metastatic Uveal Melanoma
IDEAYA Biosciences, Inc. and Servier presented complete data from the primary analysis of their registrational Phase 2/3 OptimUM-02 trial of darovasertib in combination with crizotinib in first line HLAA2:01 negative metastatic uveal melanoma at the 2026 American Society of Clinical Oncology Annual Meeting. The darovasertib combination resulted in a statistically significant and clinically meaningful improvement in median progression-free survival versus investigator's choice of therapy – 6.9 months versus 3.1 months, HR: 0.42, 58% reduction in risk of disease progression. The combination significantly improved overall response rate (37.1% vs 5.8%) and disease control rate (73.3% vs. 31.1%) by blinded independent central review versus investigator's choice of therapy, where approximately 77% were treated with ipilimumab plus nivolumab. Overall survival was not yet mature but showed an early trend favoring the darovasertib combination, with the next update targeted as part of the pre-specified interim analysis. The darovasertib combination demonstrated a manageable safety profile consistent with prior results, with a low rate of treatment-related serious adverse events (9.2%) and discontinuations due to treatment-related adverse events for darovasertib (2.5%) and crizotinib (10%). The NDA submission is in process under the Real-time Oncology Review program, with the filing expected to be completed in the second half of 2026. OptimUM-02 is a global, registrational Phase 2/3 trial evaluating a total of 313 patients with first line HLA*A2:01 negative metastatic uveal melanoma, randomized 2:1 to the darovasertib combination or an investigator's choice of therapy arm reflective of real-world clinical practice that included ipilimumab plus nivolumab or pembrolizumab. The primary endpoint to support accelerated approval is median progression-free survival as assessed by blinded independent central review. Secondary endpoints include safety and investigator assessed progression-free survival, overall response rate, disease control rate and duration of response. The trial met the primary endpoint, with patients treated with the darovasertib combination demonstrating a statistically significant improvement in median progression-free survival of 6.9 months versus 3.1 months in the investigator's choice of therapy arm by blinded independent central review (HR: 0.42; 95% CI: 0.30, 0.59; p-value: <0.0001). Patients treated with the darovasertib combination also had a statistically significant improvement in median progression-free survival of 6.7 months versus 2.7 months for investigator's choice of therapy by investigator assessment (HR: 0.36; 95% CI: 0.26, 0.50, p-value: <0.0001). The darovasertib combination reduced the risk of disease progression by 58% and 64% as assessed by blinded independent central review and investigator assessment, respectively. Treatment with the darovasertib combination demonstrated a consistent and meaningful improvement in median progression-free survival relative to the investigator's choice of therapy arm across a broad range of patient subgroups, including age and gender, type of immune therapy used in investigator's choice of therapy, LDH stratification, ECOG status and site of metastasis. Patients treated with the darovasertib combination had an overall response rate of 37.1% (78/210) and 39.5% (83/210) as assessed by blinded independent central review and investigator, respectively, compared to 5.8% (6/103) and 1.9% (2/103) in the investigator's choice of therapy arm (p-value: <0.0001). The darovasertib combination led to a disease control rate of 73.3% (154/210) and 74.3% (156/210) by blinded independent central review and investigator assessment, respectively, compared to 31.1% (32/103) and 27.2% (28/103) in the investigator's choice of therapy control arm. The median duration of response was 6.8 months (95% CI: 5.5, 11.3) by blinded independent central review and 6.8 months (95% CI: 4.8, 9.7) by investigator assessment based on a median follow-up time of 7.4 months as of the cutoff date. As noted in the topline results, data on overall survival was still immature as of the cutoff date, however, there was an early trend in overall survival improvement in the darovasertib combination arm relative to the investigator's choice of therapy arm. IDEAYA will provide the next overall survival update as part of the pre-specified interim analysis. Overall survival data, when available, will be used to support a potential full approval in the United States and globally. The darovasertib combination was generally well-tolerated with a manageable safety profile consistent with previous results and known side-effects of each agent alone. Median relative dose intensities of darovasertib and crizotinib were 91.0% and 77.1%, respectively, compared to 100% for the investigator's choice of therapy arm. Grade 3/4 treatment-related adverse events occurred in 40.6% (97/239) of patients in the darovasertib combination arm compared to 37.0% (37/100) of patients in the investigator's choice of therapy control arm. Treatment-related serious adverse events were 9.2% (22/239) and 25.0% (25/100) in the darovasertib combination and investigator's choice of therapy arms, respectively. Low discontinuation rate due to treatment-related adverse events for darovasertib (2.5%) and crizotinib (10.0%) relative to investigator's choice of therapy (19.0%). The most common Grade 3/4 treatment-related adverse events included diarrhea (10.0%), syncope (7.1%) and hypotension (3.8%) in the darovasertib combination arm compared to elevated liver enzymes (ALT, 7.0% /AST, 7.0%), diarrhea (6.0%), hepatitis (5.0%) and colitis (4.0%) in the investigator's choice of therapy control arm. In April 2026, IDEAYA announced the U.S. Food and Drug Administration has agreed to review their new drug application for darovasertib in combination with crizotinib under the Oncology Center of Excellence Real-time Oncology Review program. IDEAYA completed its first pre-submission in May and expects to complete the NDA filing in the second half of 2026.
