IDEAYA Biosciences Reports Positive FDA Meeting on Phase 3 Trial Design for Darovasertib in Uveal Melanoma

IDEAYA Biosciences, Inc., a company specializing in precision medicine oncology, has announced a significant development in its efforts to advance treatments for primary uveal melanoma (UM), a rare eye cancer. The company received affirmation from the U.S. Food and Drug Administration (FDA) during a Type D meeting regarding the design for a Phase 3 registrational trial. This trial will focus on evaluating the effectiveness and safety of darovasertib as a neoadjuvant treatment for primary UM.

Darovasertib is a selective protein kinase C (PKC) inhibitor designed to target both primary and metastatic uveal melanoma (MUM). The drug has earned several designations from the FDA, including Breakthrough Therapy Designation for its use as a neoadjuvant therapy in enucleation-recommended primary UM. Additionally, it has been granted Fast Track designation when combined with crizotinib for treating metastatic UM in adults. An ongoing Phase 2/3 trial examines the combination of darovasertib and crizotinib for patients who are HLA-A2-negative with metastatic UM. Furthermore, darovasertib has received Orphan Drug status in uveal melanoma treatment.

The Phase 3 clinical trial is set to commence in the first half of 2025. The trial's design, shaped by feedback from the FDA, will involve a randomized study with around 520 participants divided into two cohorts: enucleation and plaque brachytherapy (PB). The enucleation cohort will consist of 120 patients randomized to receive darovasertib or not. Meanwhile, the PB cohort will have 400 patients, with one group receiving darovasertib followed by PB and the other receiving only PB.

Critical aspects of the trial design include primary endpoints tailored to each cohort. For the enucleation group, the primary endpoint is the eye preservation rate, which should exceed a lower bound of 10% with a 95% confidence interval. For the PB cohort, the primary endpoint focuses on the proportion of patients experiencing a significant loss of vision, defined as a 15-letter or greater loss in the Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA).

The trial also includes secondary endpoints for both patient groups. One key secondary endpoint is ensuring that there is no detriment to Event-Free Survival (EFS), with "no detriment" defined as overlapping confidence intervals. Other secondary measures include the overall response rate, the proportion of patients with severe macular edema, the percentage experiencing substantial vision loss, and those requiring a reduced radiation dose to critical eye structures.

An additional point of interest is the potential for submitting data from the enucleation cohort for regulatory review earlier than data from the PB cohort, depending on the maturity of EFS data. The planned dosage for darovasertib in this trial phase is 300mg twice daily.

IDEAYA Biosciences is committed to using molecular diagnostics to develop targeted therapeutics in precision oncology. Their approach involves integrating biomarker identification and validation with innovative drug discovery, especially focusing on synthetic lethality as a promising category in precision medicine.

This progress marks an important milestone for IDEAYA, as it continues to explore and develop innovative solutions for combating challenging cancers such as uveal melanoma. The support from the FDA and the structured approach to the upcoming trial underline the promising potential of darovasertib as a treatment option.