Study of Adjuvant Darovasertib and Crizotinib in Participants With Primary Non-metastatic Uveal Melanoma

A Randomized, Phase 3, Open-label Study of Adjuvant Darovasertib and Crizotinib in Participants With Primary Non-metastatic Uveal Melanoma

This is a randomized, multi-center, open-label study of adjuvant darovasertib in participants with non-metastatic uveal melanoma (OptimUM-11)

Study Overview

• Status: Recruiting
• Conditions: Uveal Melanoma
• Intervention / Treatment: Drug: Darovasertib; Drug: Crizotinib (Xalkori)

Detailed Description

This study will enroll participants who are at high-risk for metastatic disease and who have completed primary local therapy (i.e., plaque brachytherapy, proton beam radiation, or enucleation) for their UM without evidence of active local or metastatic disease after this treatment.

The Treatment Arm will have participants who have completed PLT and will receive darovasertib + crizotinib.

The Observation Arm participants will not receive darovasertib + crizotinib but will be observed and followed for disease recurrence and survival (Control Arm)

Participants in both arms will be followed for up to five years to assess longer term outcomes such as tumor recurrence and survival.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: IDEAYA Clinical Trials; Phone Number: +1-855-433-2246; Email: IDEAYAClinicalTrials@ideayabio.com
• Study Contact Backup: Name: Holger Thurm; Email: hthurm@ideayabio.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
      • Contact: Marcus Butler, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Primary Uveal Melanoma, classified as high-risk of relapse (AJCC Stage II or Stage 3)
• Completed primary local therapy (enucleation, proton beam therapy, plaque brachytherapy)
• ECOG performance status of 0 or 1
• Adequate organ function
• Age 18 or older
• Written informed consent and ability to comply
• Primary local therapy completed within 120 days before C1D1/randomization.
• Contraception requirements

Exclusion Criteria:

• Previous systemic treatment for Uveal Melanoma
• Clinical or radiological evidence of metastatic UM
• Concurrent malignant disease with the following exceptions: malignancies that were treated curatively and have not recurred within 2 years prior to randomization, completely resected basal cell and squamous cell skin cancers, any malignancy considered to be indolent and never required systemic therapy, and any type of carcinoma in situ receiving curative therapy (resection)
• Known AIDS related illness
• History of interstitial lung disease, active pneumonitis, or history of noninfectious pneumonitis requiring steroids
• History of syncope may be exclusionary, but will be reviewed on a case-by-case basis
• Active Hepatitis B or C infection
• Any gastrointestinal condition (eg, inflammatory bowel disease, major gastric or intestinal surgery) that could affect absorption or ability to swallow
• Females who are pregnant or breastfeeding
• Impaired cardiac function
• History of stroke within the last 6 months of randomization
• Ongoing use of medication use for infections, other antineoplastic therapies, or other prohibited medications, including medications that interact with the metabolism of darovasertib+crizotinib
• allergy to mammalian meat products or gelatin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Participant Group/Arm: Treatment combination dose of IDE196 + crizotinib will be tested	Drug: Darovasertib; Oral, selectively targets key proteins; Drug: Crizotinib (Xalkori); Oral small molecule
No Intervention: Observation; Participant Group/Arm: Observation Standard of care observation & follow-up (no treatment)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median relapse-free survival	Time to local recurrence or metastatic disease per Blinded Independent Central Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)	Approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median metastasis-free survival	Median MFS, defined as the time from randomization to the date of metastatic disease (outside of the eye or orbit) by BICR per RECIST v 1.1	Approximately 5 years
Overall survival	Overall survival with darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM with no evidence of metastatic disease who are at high-risk for recurrence	Approximately 5 years
Median UM specific survival	Median UM specific survival defined as the time from randomization to the date of death due to UM	Approximately 5 years
Median metastasis-free survival	Median MFS, defined as the time from randomization to the date of metastatic disease (outside of the eye or orbit) as assessed by investigator	Approximately 5 years
Safety, and severity of occurrence of adverse events (AEs) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) V6.0 or later	To assess safety and tolerability of darovasertib + crizotinib in participants who have completed PLT for primary UM	Approximately 3 years
Change from baseline over time and across Treatment Arms as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30)	Compare quality of life outcomes of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM	Approximately 5 years
Recurrence-free suvival	Compare RFS of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM with no evidence of metastatic disease and who are at high-risk for recurrence	Approximately 5 years
Metastasis-Free Survival	Compare MFS of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM with no evidence of metastatic disease and who are at high-risk for recurrence	Approximately 5 years
Median Local Recurrence-Free Survival	Compare local RFS (LRFS) of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM with no evidence of metastatic disease and who are at high-risk for recurrence	Approximately 5 years
Change from baseline over time and across Treatment Arms as measured by European Quality of Life Questionnaire EQ-5D-5L.	Compare quality of life outcomes of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM	[Time Frame: Approximately 5 years]
Change from baseline over time and across Treatment Arms as measured by EORTC Oncology Quality of Life Questionnaire Ophthalmic-30 (EORTC QLQ-OPT30)	Compare quality of life outcomes of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM	[Time Frame: Approximately 5 years]

Collaborators and Investigators

• Sponsor: IDEAYA Biosciences

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2034
• Study Completion (Estimated): April 1, 2034

Study Registration Dates

• First Submitted: August 21, 2026
• First Submitted That Met QC Criteria: August 31, 2026
• First Posted (Actual): September 4, 2026

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Adjuvant; Uveal Melanoma; Choroidal Melanoma; Ocular Melanoma; enucleation; Ocular Oncology; Crizotinib; proton beam; Protein Kinase C; GNAQ; Darovasertib; GNA11; IDE 196; plaque brachytherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Uveal Diseases; Melanoma; Uveal Neoplasms; Uveal Melanoma; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines; Aminopyridines; Crizotinib
• Other Study ID Numbers: IDE196-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No