IDEAYA and Servier Dose First Patient in Phase III OptimUM-11 Adjuvant Trial of Darovasertib Plus Crizotinib in Uveal Melanoma
核心洞察
IDEAYA Biosciences and Servier have dosed the first patient in OptimUM-11, a global Phase III registrational trial of darovasertib plus crizotinib as adjuvant therapy in primary uveal melanoma (搜索).
The trial will enroll approximately 450 patients at elevated risk of metastatic recurrence after local therapy, randomizing them 1:1 to 12 months of the combination or observation.
Relapse-free survival is the primary endpoint in a setting where no adjuvant treatment is currently approved, despite up to 50% of patients developing metastatic disease.
IDEAYA Biosciences (Nasdaq: IDYA) and 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 (搜索) at elevated risk of metastatic recurrence. The setting currently has no approved adjuvant treatment options.
Uveal melanoma (搜索) is a rare but aggressive eye cancer. The disease is driven in nearly all cases by activating mutations in GNAQ (搜索) or GNA11 (搜索), which constitutively activate protein kinase C (搜索) (PKC) signaling. Darovasertib is a first-in-class oral PKC inhibitor that acts on isoforms downstream of these mutations, while crizotinib is an oral cMET (搜索) inhibitor targeting 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.
Trial Design and Endpoints
OptimUM-11 is expected to enroll approximately 450 patients globally 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-crizotinib combination for 12 months or to observation. The primary endpoint is relapse-free survival.
"Dr. Darrin Beaupre, Chief Medical Officer of IDEAYA, said dosing the first patient marks an important milestone in advancing darovasertib across the uveal melanoma (搜索) patient journey," and emphasized the urgent need for systemic therapies to delay or prevent metastatic recurrence.
Arnaud Lallouette, Executive Vice President of Global Medical & Patient Affairs at Servier, added that preventing or delaying recurrence could fundamentally change the treatment journey for high-risk patients, underscoring the potential of the darovasertib-crizotinib combination.
Commercial Terms and Regulatory Rights
IDEAYA retains US regulatory and commercial rights to darovasertib, while 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. Both companies will share development costs as the trial progresses.
Supporting Data Across the Darovasertib Program
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 (搜索), 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 (搜索), 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.
Competitive Landscape
The only approved therapy in the broader metastatic uveal melanoma (搜索) setting is Immunocore (搜索)'s Kimmtrak (tebentafusp-tebn (搜索)), which is restricted to HLA-A*02:01-positive patients and is administered intravenously. The darovasertib program targets the complementary HLA-negative majority in the metastatic setting and addresses primary disease in the neoadjuvant and adjuvant settings.
With OptimUM-11 now enrolling, IDEAYA said darovasertib is running in three randomized Phase III registrational trials simultaneously across the metastatic, neoadjuvant and adjuvant uveal melanoma (搜索) settings. The NDA filing timeline for metastatic disease, expected to complete in H2 2026, represents the nearest regulatory milestone for the program.