Ideaya Biosciences is advancing its investigational drug, darovasertib, to a Phase 3 clinical trial for neoadjuvant uveal melanoma (UM) after promising Phase 2 results and a successful Type C meeting with the FDA. The drug has shown potential in reducing tumor size and preserving vision in patients with this rare eye cancer.
The interim Phase 2 data, presented September 23, 2024, included 49 evaluable patients and demonstrated that approximately 49% of patients experienced greater than 30% tumor shrinkage, as measured by product of diameters. Importantly, the study also reported a ~61% eye preservation rate for patients undergoing enucleation. These results suggest a clinically meaningful benefit for patients with neoadjuvant UM, where there are currently no FDA-approved therapies.
Clinical Efficacy and Safety
The Phase 2 trial (NCT05907954) and an investigator-sponsored trial (IST, NCT05187884) evaluated darovasertib as a neoadjuvant treatment for UM. Key findings include:
- Approximately 59% of patients (29 out of 49) showed greater than 20% ocular tumor shrinkage.
- Evidence of visual preservation was observed through reduced radiation associated with plaque brachytherapy.
- The adverse event profile was manageable, with 11% grade 3 or higher AEs and a 5% serious AE rate. The discontinuation rate was 3%, with common AEs including diarrhea, nausea, vomiting, and fatigue.
Dr. Carol L. Shields, Chief of the Ocular Oncology Service at Wills Eye Hospital, noted, "Darovasertib has demonstrated compelling preliminary clinical efficacy and a favorable AE profile... with approximately 61% eye preservation rate for enucleation patients...[it] has the potential to provide a new standard of care in this setting."
Phase 3 Trial Design and Regulatory Path
Following constructive feedback from the FDA in a Type C meeting, Ideaya is moving forward with a Phase 3 randomized clinical trial. The trial is projected to enroll approximately 400 patients, randomized to either darovasertib or a control arm. The study will include two cohorts: patients eligible for enucleation and those eligible for plaque brachytherapy.
The primary endpoints for the Phase 3 trial, based on FDA guidance, will be eye preservation rate for enucleation patients and time to vision loss for plaque brachytherapy patients. A secondary endpoint will be no detriment to Event-Free Survival (EFS) in the treatment arms.
IDEAYA is also in discussions with the FDA to include Overall Response Rate (ORR) as a potential surrogate and composite endpoint to support earlier approval scenarios. The company aims to secure a broad indication label in neoadjuvant UM for subjects with low, intermediate, and high risk for metastatic disease.
Market Opportunity
Uveal melanoma is the most common type of eye cancer in adults, with an estimated annual incidence of approximately 12,000 patients in North America, Europe, and Australia. Currently, there are no FDA-approved therapies for neoadjuvant UM, representing a significant unmet medical need.
Dr. Darrin Beaupre, Chief Medical Officer of IDEAYA Biosciences, stated, "Based on the highly promising preliminary clinical efficacy and manageable safety profile observed with darovasertib and the high unmet medical need of neoadjuvant UM, we are excited to advance darovasertib rapidly to a registrational trial in this indication."
IDEAYA retains all commercial rights to darovasertib, subject to certain economic obligations under its license agreement with Novartis.
