IDEAYA Shares Positive Phase II Data for Darovasertib and Plans for Future Phase III Trial

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IDEAYA Biosciences has shared positive interim Phase II data for darovasertib in neoadjuvant uveal melanoma (UM). Additionally, IDEAYA shared details from a successful FDA meeting on its plans for a Phase III trial in neoadjuvant UM.¹

Results from the Phase II study were highlighted by 49% of patients experiencing a >30% tumor shrinkage. Additional findings include:

• Evidence of visual preservation observed by reducing the amount of radiation associated with plaque brachytherapy.
• Manageable adverse event (AE) profile observed, including 11% grade 3 or higher AEs, and 5% serious AE rate with a discontinuation rate of 3%. The most common AEs observed included diarrhea, nausea, vomiting, and fatigue.

In a press release, Carol L. Shields, MD, chief of the ocular oncology service at Wills Eye Hospital and professor of ophthalmology at Thomas Jefferson University said, "Darovasertib has demonstrated compelling preliminary clinical efficacy and a favorable AE profile in the neoadjuvant UM setting, with approximately 49% of patients demonstrating greater than 30% tumor shrinkage and importantly approximately 61% eye preservation rate for enucleation patients.The primary clinical endpoints supported by discussions with the FDA of eye preservation and time to vision loss are clinically meaningful for neoadjuvant UM patients, and darovasertib has the potential to provide a new standard of care in this setting.”

The Phase II study, IDE196-009 (NCT05907954), is a multi-center, open-label, company-sponsored trial evaluating darovasertib as neoadjuvant treatment for UM prior to primary interventional treatment of enucleation or radiation therapy and as adjuvant therapy following the primary treatment.

With positive results from its Phase II trial, IDEAYA is now eyeing a randomized Phase III study in neoadjuvant UM. The company currently expects to randomize 400 patients for treatment with darovasertib in the treatment arm or the control arm. There are plans for 2 cohorts: enucleation eligible UM patients and plaque brachytherapy eligible UM patients.

"The successful FDA Type C meeting provides darovasertib a potential registrational path in neoadjuvant UM, using primary clinical endpoints of eye preservation and time to vision loss, with no detriment to EFS in the treatment arms as a secondary endpoint.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," Darrin Beaupre, MD, PhD, chief medical officer, IDEAYA Biosciences, said in the press release.

Some other highlights of the Phase III trial design include:

• Eye preservation rate is the primary endpoint for enucleation UM patients. Time to vision loss is the primary endpoint for plaque brachytherapy UM patients.
• No detriment to event-free-survival in the treatment arms is a secondary endpoint.
• Discussions are ongoing with the FDA to include overall response rate as a potential surrogate and composite endpoint to support earlier approval scenarios.
• The study will enroll UM patients with high risk for metastatic disease. Based on preliminary projections.
• 300mg BID darovasertib noted in FDA briefing book as the move-forward dose.

Reference

1. IDEAYA Biosciences Announces Positive Interim Phase 2 Data for Darovasertib and Successful FDA Type C Meeting on Registrational Trial Design for Regulatory Approval in Neoadjuvant Uveal Melanoma. News release. IDEAYA Biosciences. September 23, 2024. Accessed September 24, 2024. https://ir.ideayabio.com/2024-09-23-IDEAYA-Biosciences-Announces-Positive-Interim-Phase-2-Data-for-Darovasertib-and-Successful-FDA-Type-C-Meeting-on-Registrational-Trial-Design-for-Regulatory-Approval-in-Neoadjuvant-Uveal-Melanoma