Darovasertib plus crizotinib vs investigator’s choice as first-line treatment for patients with HLA-A2 negative metastatic uveal melanoma: Primary results from the OptimUM-02 trial.

作者：Marlana Orloff, Egle Ramelyte, Marcus O. Butler, Piotr Rutkowski, Lorenza Di Guardo, M S Carlino, Bartosz Chmielowski, Lucy Boyce Kennedy, Kamaneh Montazeri, Joseph J. Sacco, Ernesto Rossi, Victoria Atkinson, Rizwan Haq, Meredith McKean, G.W. Cole, Hetal Patel, Long Kwei, Jasgit C. Sachdev, Darrin M. Beaupre, Sophie Piperno‐Neumann · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.17_suppl.lba9503 · 被引用次数：2 · 研究领域：Ocular Oncology and Treatments、Melanoma and MAPK Pathways、Ocular Diseases and Behçet’s Syndrome

LBA9503 Background: Uveal melanoma (UM) is the most common ocular cancer in adults with up to 50% of patients developing metastasis with high mortality. No FDA-approved systemic treatments exist for HLA-A*02:01 (HLA-A2) -negative metastatic UM (mUM), and therapies effective in other melanoma subtypes have limited efficacy. Darovasertib (darova) is a first-in-class, oral PKC inhibitor that showed encouraging clinical outcomes in a prior phase 1/2 study in combination with the MET inhibitor crizotinib (crizo). Here we present primary safety & efficacy results from the nested phase 2/3 OptimUM-02 trial of darova+crizo as first-line treatment for HLA-A2 negative-mUM. Methods: OptimUM-02 is an open-label study of HLA-A2 negative first-line mUM patients who were randomized 2:1 to receive darova 300 mg plus crizo 200 mg BID or investigator’s choice (IC) of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine). The primary endpoint for efficacy for phase 2 was progression-free survival (PFS) by RECIST (BICR). Other endpoints included investigator assessed PFS (PFS inv ), objective response rate (ORR), duration of response (DOR), disease control rate (DCR: CR+ PR + SD ≥ 12 weeks), and safety. Overall survival, the phase 3 primary endpoint, will be presented as the data matures. Results: Overall 338 patients received at least one dose of study treatment (safety population), 313 comprised the efficacy population. The median PFS by BICR was 6.9 months for darova+crizo (5....