IDEAYA Announces Phase 2 Darovasertib Results in Uveal Melanoma at ASCO and Clinical Update

IDEAYA Biosciences, Inc., a precision medicine oncology company, has shared promising results from its ongoing Phase 2 trial of darovasertib, a novel oral inhibitor targeting protein kinase C (PKC), for the treatment of uveal melanoma (UM). The data was presented at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting.

The trial results highlight darovasertib's potential as a neoadjuvant treatment, particularly in preserving the eye and reducing tumor size in UM patients. According to Yujiro S. Hata, President and CEO of IDEAYA Biosciences, the therapy could meet significant unmet medical needs, expanding treatment opportunities beyond the metastatic setting and regardless of HLA-A2 status.

Anthony Joshua, the lead investigator of the study and Head of Medical Oncology at Kinghorn Cancer Centre, presented the findings from the Phase 2 Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma (NADOM). The trial involved 15 patients scheduled for enucleation, treated with darovasertib at a dose of 300mg twice daily. After an initial safety cohort of three patients, the remaining 12 underwent treatment for up to six months before their primary intervention, which included enucleation, plaque brachytherapy, or external beam radiotherapy (EBRT).

As of May 14, 2024, thirteen patients had completed the neoadjuvant treatment, with 11 receiving adjuvant darovasertib following primary UM treatment. Of these, five completed the planned six-month therapy. The results showed that 75% of the 12 enucleation patients had eye preservation, converting to plaque brachytherapy or EBRT. Additionally, 67% of these patients experienced more than 30% tumor shrinkage, with a median shrinkage of 47%.

The treatment displayed a manageable adverse event (AE) profile, with no serious drug-related AEs and predominantly Grade 1 or 2 drug-related AEs. About 20% of patients reported at least one Grade 3 drug-related AE.

IDEAYA is planning a Type C meeting with the FDA in the second half of 2024 to discuss the potential for a registrational trial for darovasertib in the neoadjuvant UM setting. The company has also activated over 14 global sites for its Phase 2 company-sponsored trial and enrolled over 40 patients. Preliminary data from this trial, which includes patients with at least four months of darovasertib treatment, indicated a median tumor shrinkage of approximately 72% by volume, with most enucleation patients experiencing eye preservation.

Darovasertib is also being evaluated in a potential registrational Phase 2/3 trial for first-line HLA-A2-negative metastatic UM (MUM), and Phase 2 trials for HLA-A2 positive MUM and neoadjuvant/adjuvant UM. The program has received FDA Fast Track and Orphan Drug designations for uveal melanoma treatment, including MUM.

The global annual incidence of primary UM is estimated to be between 8,000 and 10,000 patients, predominantly in the U.S. and Europe. IDEAYA’s commitment to precision medicine involves discovering and developing targeted therapies for patients identified through molecular diagnostics, focusing on synthetic lethality—a promising area in precision oncology.

The positive clinical data and the forward-looking plans underscore IDEAYA's dedication to advancing darovasertib as a transformative treatment for UM, potentially improving outcomes and preserving patients' vision.