San Francisco-based IDEAYA Biosciences (Nasdaq: IDYA) and France-based Servier announced that the first patient has been dosed in OptimUM-11, a global Phase III registrational trial evaluating darovasertib in combination with crizotinib as adjuvant therapy for patients with primary uveal melanoma at elevated risk of metastatic recurrence, a setting with no approved adjuvant treatment options.
Uveal melanoma is driven in nearly all cases by activating mutations in GNAQ or GNA11, which constitutively activate protein kinase C (PKC) signaling. Darovasertib inhibits PKC isoforms downstream of GNAQ/GNA11 mutations, while crizotinib inhibits cMET signaling that may contribute to resistance. Despite effective local control of the primary tumor through radiotherapy or enucleation, up to 50% of patients eventually develop metastatic disease, and no adjuvant therapy has been approved to reduce that risk.
OptimUM-11 is expected to enroll approximately 450 patients who have completed primary local therapy and have an increased risk of metastasis. Patients are eligible irrespective of HLA status and will be randomized 1:1 to receive the darovasertib combination for 12 months or observation. The primary endpoint is relapse-free survival. IDEAYA retains US regulatory and commercial rights to darovasertib; Servier holds all rights outside the US under an exclusive license agreement struck in September 2025 that included a USD 210 million upfront payment and up to USD 320 million in milestones.
In April 2026, IDEAYA and Servier reported that the Phase II/III OptimUM-02 trial met its primary endpoint in first-line HLA-A*02:01-negative metastatic uveal melanoma, with the combination reducing the risk of disease progression by 58% versus investigator choice of therapy (HR: 0.42; median PFS 6.9 vs. 3.1 months; p<0.0001). IDEAYA has initiated an NDA submission under the FDA's Real-Time Oncology Review program, with completion of the full filing expected in the second half of 2026. Separately, a Phase III neoadjuvant trial (OptimUM-10) is enrolling in primary uveal melanoma, supported by Breakthrough Therapy Designation granted by the FDA in March 2025 and positive Phase II data presented at ESMO 2025 showing a 57% eye preservation rate in enucleation-recommended patients.