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)

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.

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