IDEAYA Biosciences Completes Enrollment in Pivotal Trial for Darovasertib Combination in Metastatic Uveal Melanoma
Key Insights
IDEAYA Biosciences has completed enrollment of 435 patients in its Phase 2/3 OptimUM-02 trial evaluating darovasertib plus crizotinib for first-line treatment of HLA*A2-negative metastatic uveal melanoma (search).
The company expects to report median progression-free survival data in Q1 2026 to support a potential accelerated approval filing in the United States.
Previous Phase 1/2 trial data demonstrated a 21.1-month median overall survival and 7.0-month median progression-free survival with the combination therapy.
IDEAYA Biosciences has reached a critical milestone in developing a potential first-line treatment for metastatic uveal melanoma (search), completing enrollment of 435 patients in its pivotal Phase 2/3 trial evaluating darovasertib in combination with crizotinib. The registration-enabling OptimUM-02 trial targets HLA*A2-negative metastatic uveal melanoma, a rare and aggressive form of ocular cancer (search) with limited treatment options and historically poor survival outcomes.
The South San Francisco-based precision medicine oncology company announced that topline data, including median progression-free survival (PFS), are expected in the first quarter of 2026 to support a potential accelerated approval filing in the United States. Median overall survival data from OptimUM-02 will subsequently be used to support a potential full approval filing.
Trial Design and Regulatory Strategy
OptimUM-02 is structured as a multi-arm, multi-stage, open-label Phase 2/3 trial with patients randomized to receive either the darovasertib and crizotinib combination or investigator's choice of treatment, including pembrolizumab, ipilimumab plus nivolumab, or dacarbazine. The trial's primary endpoints are median PFS and median overall survival, designed to support both accelerated and full approval pathways in the United States.
Darovasertib, IDEAYA's investigational oral protein kinase C (search) (PKC) inhibitor, is being combined with Pfizer's crizotinib, an oral c-MET (search) inhibitor. The combination has received significant regulatory recognition, including FDA Breakthrough Therapy Designation as neoadjuvant therapy in enucleation recommended primary uveal melanoma (search) and Fast Track designation for the combination in adult patients with metastatic uveal melanoma (search).
Promising Early Clinical Data
The regulatory strategy is supported by encouraging data from the Phase 1/2 OptimUM-01 trial, which IDEAYA presented at the Society for Melanoma Research Congress in October 2025. The single-arm Phase 2 trial demonstrated a 21.1-month median overall survival and 7.0-month median progression-free survival in first-line metastatic uveal melanoma (search) patients, including both HLAA2-negative and HLAA2-positive patients.
"We are very pleased to announce that we have achieved the target enrollment to enable potential full approval filing in our Phase 2/3 registration-enabling trial of darovasertib in combination with crizotinib in first-line HLA*A2-negative metastatic uveal melanoma (search)," said Yujiro S. Hata, President and Chief Executive Officer of IDEAYA Biosciences. "This milestone reflects both the clear unmet need in metastatic uveal melanoma, as well as the strong clinical interest in our darovasertib program."
Addressing Unmet Medical Need
Metastatic uveal melanoma (search) represents a significant unmet medical need, characterized as a rare, aggressive form of ocular cancer (search) with limited treatment options and historically poor survival outcomes. The completion of enrollment in OptimUM-02 reflects both the clinical urgency and the strong interest from the medical community in developing effective treatments for this devastating disease.
Hata emphasized the clinical potential demonstrated in early trials: "Moreover, the promising overall survival data and broader clinical efficacy demonstrated in the recently reported median overall survival results from the Phase 1/2 clinical trial (OptimUM-01) of this combination in metastatic uveal melanoma (search) are indicative of the clinical potential of darovasertib to meaningfully impact patients with this devastating disease."
Broader Development Program
Beyond the metastatic setting, IDEAYA is advancing darovasertib in earlier stages of uveal melanoma (search). The company is currently enrolling patients in a pivotal Phase 3 trial of single-agent darovasertib in the neoadjuvant setting of primary uveal melanoma (OptimUM-10). Darovasertib has also been designated as an Orphan Drug by the U.S. FDA in uveal melanoma, including in metastatic disease.
The completion of OptimUM-02 enrollment positions IDEAYA to potentially deliver the first targeted therapy specifically designed for HLA*A2-negative metastatic uveal melanoma (search) patients, with the company expressing commitment to making the treatment available "as expeditiously as possible" if approved.