IDEAYA Biosciences Reports Positive Phase 2 Data and FDA Meeting Success for Darovasertib in Neoadjuvant Uveal Melanoma

IDEAYA Biosciences, Inc., a precision medicine oncology firm, announced promising interim Phase 2 clinical trial data for its drug darovasertib in treating neoadjuvant uveal melanoma (UM). The data reveal significant tumor shrinkage and eye preservation rates, and the company has had a constructive FDA Type C meeting regarding the design of a potential registrational trial.

The Phase 2 study includes 49 evaluable patients, demonstrating a substantial clinical efficacy. Approximately 49% of these patients experienced over 30% tumor shrinkage, and about 61% of patients who were candidates for eye removal (enucleation) retained their eyes. The primary clinical endpoints discussed with the FDA focus on eye preservation and time to vision loss, which are crucial for neoadjuvant UM patients. Dr. Carol L. Shields of Wills Eye Hospital noted the potential of darovasertib to establish a new standard care due to its effectiveness and safety profile.

Dr. Darrin Beaupre, Chief Medical Officer at IDEAYA, emphasized the promising nature of the preliminary data and the urgent medical need in neoadjuvant UM. He expressed optimism about swiftly moving towards a registrational trial.

Darovasertib is a potent and selective protein kinase C (PKC) inhibitor, currently undergoing evaluation in four clinical trials. Notably, it has shown FDA Fast Track designation when combined with crizotinib for metastatic uveal melanoma (MUM). The ongoing Phase 2 trial (IDE196-009) investigates darovasertib's effectiveness as a neoadjuvant treatment before primary interventions like enucleation or radiation, and as an adjuvant therapy post-primary treatment. An additional investigator-sponsored trial (NCT05187884) is also assessing its neoadjuvant use.

The recent data update from the Phase 2 trial, with a cut-off date of August 15, 2024, indicates further evidence of darovasertib's clinical activity. Key findings include:
- 31 enucleation patients and 18 plaque brachytherapy patients were evaluable.
- 59% of these patients achieved more than 20% ocular tumor shrinkage.
- 49% saw more than 30% tumor shrinkage.
- A 61% eye preservation rate was observed in enucleation patients.
- Visual preservation was noted by reducing radiation exposure in plaque brachytherapy patients.
- The safety profile was manageable, with a low rate of severe adverse events.

IDEAYA plans to initiate a Phase 3 randomized clinical trial, incorporating FDA guidance from their recent meeting. This trial is expected to enroll approximately 400 patients, divided into two cohorts: enucleation-eligible and plaque brachytherapy-eligible patients. For the enucleation cohort, patients will be randomized to receive darovasertib as a neoadjuvant therapy or not. For the plaque brachytherapy cohort, the allocation will be between darovasertib followed by brachytherapy or brachytherapy alone.

Key points of the proposed Phase 3 trial design include:
- Eye preservation rate as the primary endpoint for enucleation patients.
- Time to vision loss as the primary endpoint for plaque brachytherapy patients.
- No detriment to Event-Free-Survival (EFS) as a secondary endpoint.
- Ongoing discussions with the FDA to include overall response rate (ORR) as a potential surrogate endpoint to support earlier approval scenarios.
- The proposed registrational study will target patients at high risk for metastatic disease.

Neoadjuvant UM presents a significant opportunity for darovasertib, with an estimated annual incidence of around 12,000 patients in North America, Europe, and Australia. IDEAYA retains all commercial rights for darovasertib, subject to certain obligations to Novartis under their exclusive license agreement.

IDEAYA will host a webcast and conference call to discuss the Phase 2 data and the proposed registrational trial. Key presenters include Dr. Carol L. Shields and IDEAYA's management team, who will provide detailed insights into the trial results and future plans.