Darovasertib and Crizotinib First-Line Treatment for Metastatic Uveal Melanoma: Overall Survival, Efficacy, and Safety From the OptimUM-01 Study

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.

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Journal
Journal of Clinical Oncology
Published
2026-10-28
DOI
https://doi.org/10.1200/jco-26-00802
Primary Topic
Ocular Oncology and Treatments
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article
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article

Darovasertib and Crizotinib First-Line Treatment for Metastatic Uveal Melanoma: Overall Survival, Efficacy, and Safety From the OptimUM-01 Study

Darrin M. Beaupre, Meredith Ann McKean, Marcus Otho Butler, Fadi Kayali et al.
5 links
Journal of Clinical Oncology
Ocular Oncology and Treatments
article

Darovasertib and Crizotinib First-Line Treatment for Metastatic Uveal Melanoma: Overall Survival, Efficacy, and Safety From the OptimUM-01 Study

Darrin M. Beaupre, Meredith Ann McKean, Marcus Otho Butler, Fadi Kayali, Agnes Lee Ang, Kevin B. Kim, Long Kwei, Kelly Barrios, Ryan Michael Weight, Jordi Ahnert Rodon, Marlana M. Orloff, Bartosz Chmielowski, Jasgit C. Sachdev, Trisha Michel Wise-Draper, Keith D. Wilner, Asad Javed, George W. Cole, Gerald Steven Falchook, Filip Jankú, Rony M. Abou-Jawde, Justin C. Moser, Matteo Salvatore Carlino, Richard D. Carvajal, April K.S. Salama, Shaheer A. Khan, Victoria G. Atkinson, Sreenivasa Chandana, Lucy Kennedy, Vijay Patel, Jordi Ahnert, Alexander Wei, Mohammed Milhem, James Reeves, Ebenezer Kio
article en

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.

Journal of Clinical Oncology
Sutter Health (US), The University of Sydney (AU), Northwell Health (US), The University of Texas MD Anderson Cancer Center (US), University of California, Los Angeles (US), Duke University (US), Pfizer (United States) (US), University of Toronto (CA), Thomas Jefferson University Hospital (US), Blacktown & Mount Druitt Hospital (AU), Princess Margaret Cancer Centre (CA), Westmead Hospital (AU), Sarah Cannon (US), Ideaya Biosciences (United States) (US), Sidney Kimmel Cancer Center (US), Melanoma Institute Australia (AU), HonorHealth (US), UCLA Jonsson Comprehensive Cancer Center (US), Duke Cancer Institute (US), Arizona State University (US), University of Cincinnati (US)
Good health and well-being
Openalex Percentile: Top 9%
Ocular Oncology and Treatments
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