On April 14, 2025 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a successful FDA Type D meeting on the Phase 3 registrational trial design that will assess the safety and efficacy of darovasertib for potential regulatory approval as neoadjuvant therapy for primary uveal melanoma (UM) (Press release, Ideaya Biosciences, APR 14, 2025, View Source [SID1234651919]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The successful FDA Type D meeting provides darovasertib a registrational path as neoadjuvant therapy for UM, using primary clinical endpoints of eye preservation and proportion of patients with vision loss, with no detriment to EFS as a secondary endpoint required for both cohorts. Based on the promising clinical efficacy and safety observed with darovasertib in the neoadjuvant setting in over 90 patients and the recent Breakthrough Therapy Designation by the US FDA, we are excited to advance the darovasertib program into our second registrational trial," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

Darovasertib is a potent and selective protein kinase C (PKC) inhibitor being developed to broadly address primary and metastatic UM (MUM). Darovasertib has received U.S. FDA Breakthrough Therapy Designation as neoadjuvant therapy in enucleation recommended primary UM and Fast Track designation for darovasertib in combination with crizotinib in adult patients with metastatic uveal melanoma (MUM), where a Phase 2/3 registration-enabling trial of the darovasertib and crizotinib combination in 1L HLA-A2-negative MUM is ongoing. Darovasertib has also been designated as an Orphan Drug by the U.S. FDA in UM, including in MUM.

FDA Guidance from the Type D Meeting on the Phase 3 Neoadjuvant Darovasertib Registrational Trial Design for Potential Regulatory Approval in Primary UM

IDEAYA is targeting to initiate the Phase 3 randomized clinical trial evaluating neoadjuvant darovasertib in primary UM in the first half of 2025. The randomized Phase 3 clinical trial design incorporates guidance and feedback from the U.S. FDA following a recent Type D meeting.

In the Phase 3 clinical trial, we currently project approximately 520 patients will be randomized 2:1 to the darovasertib treatment versus control arm. There will be 2 cohorts enrolled: 1) 120 enucleation eligible UM patients, 2) 400 PB eligible UM patients. For the enucleation cohort, the randomization will be with or without darovasertib as neoadjuvant therapy. For the PB cohort, the randomization will be darovasertib followed by PB versus PB alone.

Key highlights of the Phase 3 registrational trial design in neoadjuvant UM, based on FDA guidance:

Eye preservation rate (exceed lower bound of 10% eye preservation rate with a 95% confidence interval) is the primary endpoint for the enucleation UM cohort
Proportion of patients with vision loss from the time of randomization and time of completion of PB is the primary endpoint for the plaque brachytherapy cohort. Vision detriment will be measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) of >15-letters lost
No detriment to Event-Free-Survival (EFS) is a secondary endpoint for both cohorts and is required for approval. No detriment is defined as overlapping confidence intervals
Additional secondary endpoints: Overall Response Rate (>20% ocular tumor shrinkage by product of diameters), proportion of patients with clinically significant macular edema, proportion of subjects with 20/200 vision loss or worse (legal blindness), proportion of subjects with reduction of radiation dose of >20% delivered to key eye structures
Potential to submit the enucleation cohort data for regulatory review earlier than the PB cohort pending the EFS data maturity in both cohorts
300mg BID darovasertib will be the move-forward dose for the registrational trial