NCT05987332

IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma

IDE196 (Darovasertib) in Combination With Crizotinib Versus Investigator's Choice of Treatment as First-line Therapy in HLA-A2 Negative Metastatic Uveal Melanoma (DAR-UM-2)

• Status: Active Not Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 420 (estimated)
• Sponsor: IDEAYA Biosciences · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 2/3, multi-arm, multi-stage, open-label study of human leukocyte antigen (HLA)-A\*02:01 negative participants with metastatic uveal melanoma (MUM) who will be randomized to receive either IDE196 + crizotinib or investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).

Detailed description

This study is designed as a multi-stage Phase 2 study within a Phase 3 study to evaluate the safety, tolerability, pharmacokinetics, dose-exposure relationship, and anti-tumor activity of IDE196 in combination with crizotinib compared to the comparator arm of investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine). The Phase 2a dose optimization stage will evaluate two doses of IDE196 in combination with crizotinib compared to the comparator arm. Participants will be randomized to the three treatment arms. At the point of optimal IDE196 + crizotinib dose selection, the other dose arm will be dropped with discontinuation of enrollment to that arm. Participants receiving the IDE196 dose (in combination with crizotinib) that is not selected, will be offered the choice to remain on the same dose or change to the chosen optimal dose. The optimal dose will be chosen to complete the Phase 2b portion. The Phase 2b part of the study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared with the comparator arm. Participants will be randomized to the two treatment arms. The Phase 3 part of the study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared with the comparator arm. Participants will be randomized to the two treatment arms to evaluate the primary endpoint of overall survival (OS).

Conditions

• Metastatic Uveal Melanoma

Interventions

Type	Name	Description
DRUG	IDE196	Dosed orally, twice daily
DRUG	Crizotinib	Dosed orally, twice daily
DRUG	Pembrolizumab	IV administration every 3 weeks
DRUG	Ipilimumab	IV administration every 3 weeks for 4 Cycles
DRUG	Nivolumab	IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance
DRUG	Dacarbazine	IV administration every 3 Weeks

Timeline

• Start date: 2023-10-31
• Primary completion: 2027-01-15
• Completion: 2028-01-15
• First posted: 2023-08-14
• Last updated: 2026-02-17

Locations

68 sites across 13 countries: United States, Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom

Regulatory

• FDA-regulated drug study