Darovasertib Plus Crizotinib Combination Demonstrates Meaningful Clinical Benefit in Metastatic Uveal Melanoma
Clinical Summary:
- Design/Population: The randomized phase 2 OPTIMUS-2 trial evaluated darovasertib plus crizotinib versus investigator’s choice therapy in treatment-naïve patients with HLA-A2-negative metastatic uveal melanoma.
- Key Outcomes: The combination improved median progression-free survival and increased objective response and disease control rates compared with investigator’s choice therapy. Benefits were observed across key clinical subgroups, with a manageable safety profile and low rates of treatment discontinuation.
- Clinical Relevance: These findings represent a significant advance for a patient population with limited treatment options and support continued development of targeted therapy strategies in metastatic uveal melanoma.
Marlana Orloff, MD, Thomas Jefferson University, Philadelphia, Pennsylvania, discusses results from the phase 2 OPTIMUS-2 trial evaluating darovasertib, a first-in-class PKC inhibitor, in combination with crizotinib for patients with treatment-naïve HLA-A2-negative metastatic uveal melanoma.
The trial met its primary end point, demonstrating a near doubling of progression-free survival (PFS) compared with investigator’s choice therapy, while also improving response and disease control rates. These findings suggest that targeting PKC-driven signaling may provide a new therapeutic option for patients with metastatic uveal melanoma and support ongoing phase 3 evaluation of the regimen.
Dr Orloff presented these results at the 2026 ASCO Annual Meeting in Chicago, Illinois.
Source:
Orloff M, Ramelyte E, Butler MO, et al. 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. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract LBA9503.
