IDEAYA Biosciences (IDYA) Study result summary

Disease background and unmet need

• Uveal melanoma is a rare, aggressive cancer with poor prognosis and limited treatment options at all stages.

• About 3,000 cases are diagnosed annually in the U.S., with half progressing to metastatic disease.

• Median overall survival for metastatic cases is 10–12 months, with a five-year survival rate of 15–20%.

• Most patients are ineligible for the only approved systemic therapy, and liver metastasis is common.

• The majority of metastatic uveal melanoma patients are HLA-A*02:01-negative, with no approved therapies for this group.

Mechanism of action and therapeutic rationale

• Darovasertib is an oral, selective PKC inhibitor targeting the primary oncogenic pathway in over 95% of UM patients.

• Activating mutations in GNAQ/11 drive PKC overactivation, leading to tumor growth.

• In metastatic UM, darovasertib is combined with crizotinib, a CMET pathway inhibitor, to address metastatic spread.

• The all-oral regimen aims to improve compliance, outcomes, and quality of life.

Study background and design

• OptimUM-02 is a pivotal, global, randomized Phase 2/3 trial in HLA-A2-negative metastatic uveal melanoma, enrolling 313–437 subjects.

• Patients were randomized 2:1 to receive darovasertib plus crizotinib or standard of care/investigator's choice therapy (ipi/nivo, pembrolizumab, or dacarbazine).

• The primary endpoint was progression-free survival (PFS) by blinded independent central review; overall survival (OS) is the key phase III endpoint.

• Secondary endpoints included investigator-assessed PFS, overall response rate (ORR), duration of response, disease control rate, safety, and quality of life.

• The study completed enrollment in December 2025.