IDEAYA Receives FDA Green Light for Darovasertib Phase 3 Trial in Uveal Melanoma

IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company focused on targeted therapeutics, announced a successful Type D meeting with the U.S. Food and Drug Administration (FDA) regarding the design of its upcoming Phase 3 registrational trial evaluating darovasertib in primary uveal melanoma (UM). The meeting confirmed a regulatory path forward for darovasertib as a potential neoadjuvant therapy in this rare and life-altering cancer.

“The successful FDA Type D meeting provides darovasertib a registrational path as neoadjuvant therapy for UM, using primary clinical endpoints of eye preservation and vision loss, with no detriment to event-free survival (EFS) as a required secondary endpoint,” said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer of IDEAYA. “With strong clinical data and the recent Breakthrough Therapy Designation from the FDA, we are excited to advance the program into our second registrational trial.”

Darovasertib is a selective and potent PKC inhibitor being developed to address both primary and metastatic uveal melanoma (MUM). The FDA has granted darovasertib Breakthrough Therapy Designation for neoadjuvant use in patients recommended for enucleation and Fast Track Designation in combination with crizotinib for metastatic disease. It has also received Orphan Drug Designation in both settings.

Phase 3 Trial Overview:

The randomized Phase 3 clinical trial is expected to begin in the first half of 2025 and will include approximately 520 patients, randomized 2:1 to darovasertib versus control. The study consists of two cohorts:

• Enucleation Cohort: 120 patients who are candidates for eye removal will be randomized to receive neoadjuvant darovasertib or no neoadjuvant therapy.

• Plaque Brachytherapy (PB) Cohort: 400 patients eligible for PB will be randomized to receive darovasertib followed by PB or PB alone.

Primary Endpoints:

• Enucleation Cohort: Eye preservation rate, with success defined as exceeding the lower bound of a 10% eye preservation rate with 95% confidence.

• PB Cohort: Proportion of patients experiencing vision loss (defined as >15-letter loss on ETDRS BCVA) between randomization and completion of PB.

Key Secondary Endpoints:

• No detriment to Event-Free Survival (EFS), defined by overlapping confidence intervals, required for approval in both cohorts.

• Overall Response Rate (tumor shrinkage >20%).

• Clinically significant macular edema.

• Vision loss to 20/200 or worse (legal blindness).

• Reduction of radiation dose to critical ocular structures by >20%.

IDEAYA also noted the possibility of submitting data from the enucleation cohort for earlier regulatory review, pending EFS data maturity.

The registrational trial will move forward with a dose of 300mg BID darovasertib.