Darovasertib and Crizotinib First-Line Treatment for Metastatic Uveal Melanoma: Overall Survival, Efficacy, and Safety From the OptimUM-01 Study
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: PURPOSE: inhibitor crizotinib, has shown responses and encouraging survival outcomes in early mUM clinical trials. Here, we present phase 2 results in first-line patients with mUM treated with darovasertib 300 mg twice a day and crizotinib 200 mg twice a day. METHODS: The OptimUM-01 study was a phase I/II, multicenter, open-label, dose escalation and expansion study of darovasertib in patients with solid tumors harboring GNAQ/11 mutations irrespective of human leukocyte antigen status; this analysis focuses on the phase II expansion in previously untreated patients with mUM. Eligibility criteria included Response Evaluation Criteria in Solid Tumors v1.1 measurable disease, Eastern Cooperative Oncology Group performance status 0-1, and adequate organ function. Study end points included safety, objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: Overall, 44 treatment-naïve patients were enrolled. The most common adverse events (AEs) were diarrhea (95.2%), nausea (84.1%), peripheral edema (61.4%), and vomiting (52.3%). The most common grade 3 or greater AEs were pulmonary embolism (9.1%) and iron deficiency anemia (6.8%). AEs leading to discontinuation occurred in three patients (6.8%). ORR was 34.1%, DOR was 9.0 months, and DCR was 90.2% at 8 weeks. The median PFS and OS were 7.0 months (95% CI, 5.0 to 8.3) and 21.1 months (95% CI, 11.9 to 20.7), respectively. CONCLUSION: Results from OptimUM-01 suggest that the combination of darovasertib and crizotinib has encouraging efficacy with a manageable safety profile and may represent a first-in-class targeted treatment option for patients with previously untreated mUM.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-26-00802
Authors: Meredith McKean, Bartosz Chmielowski, Marcus O. Butler, Richard D. Carvajal, Jordi Rodon, Matteo S. Carlino, Kevin B. Kim, Trisha M. Wise-Draper, Shaheer Khan, April K.S. Salama, Justin Moser, Agnes Ang, Kelly Barrios, Jasgit C. Sachdev, Keith D. Wilner, George W. Cole, Long Kwei, Darrin M. Beaupre, Marlana Orloff, Alexander Wei, Jordi Ahnert, Marlana Orloff, Sreenivasa Chandana, Lucy Kennedy, Gerald Falchook, Ryan Weight, Mohammed Milhem, Asad Javed, Justin Moser, Vijay Patel, Fadi Kayali, James Reeves, Rony Abou-Jawde, Ebenezer Kio, Filip Janku, Victoria Atkinson
Institutions: Sarah Cannon, University of California, Los Angeles, UCLA Jonsson Comprehensive Cancer Center, University of Toronto, Princess Margaret Cancer Centre, Northwell Health, The University of Texas MD Anderson Cancer Center, The University of Sydney, Blacktown & Mount Druitt Hospital, Westmead Hospital, Melanoma Institute Australia, Sutter Health, University of Cincinnati, Duke University, Duke Cancer Institute, HonorHealth, Arizona State University, Ideaya Biosciences (United States), Pfizer (United States), Thomas Jefferson University Hospital, Sidney Kimmel Cancer Center
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7224104579