IDEAYA Biosciences announced that the Independent Data Monitoring Committee (IDMC) has recommended a move-forward dose for Part 2a of its Phase 2/3 trial evaluating the combination of darovasertib and crizotinib. This trial targets first-line treatment for patients with HLA-A2-negative metastatic uveal melanoma (MUM). The IDMC's decision was based on observed clinical efficacy and safety, allowing the trial to proceed to Part 2b.
The trial has enrolled over 185 patients and has received Fast Track designation from the U.S. Food and Drug Administration (FDA). This designation highlights the potential of the combination therapy to address a significant unmet medical need in MUM, a disease with historically poor prognosis.
Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer of IDEAYA Biosciences, stated, "We are pleased with the recommendation of the IDMC and the selection of the move-forward dose for our potential registration-enabling trial evaluating the darovasertib and crizotinib combination in first-line HLA-A2(-) MUM patients. This allows us to complete the Part 2a portion of the study and seamlessly continue to enroll in Part 2b towards a potential accelerated approval based on the primary endpoint of median progression free survival."
Clinical Trial Details
The Phase 2/3 trial (NCT05987332) is designed to evaluate the efficacy and safety of darovasertib in combination with crizotinib in patients with first-line HLA-A2-negative MUM. The primary endpoint is median progression-free survival. The trial aims for accelerated approval based on these results.
Meredith McKean, M.D., MPH, Director of Melanoma and Skin Cancer Research at Sarah Cannon Research Institute, emphasized the importance of this advancement: "The combination of darovasertib and crizotinib as first-line treatment has shown compelling preliminary clinical results in patients with HLA-A2(-) MUM. The IDMC recommendation of the move-forward dose supports the advancement of this potentially registration-enabling Phase 2/3 trial and is an important step in bringing a new treatment option to patients with MUM. Additionally, the continued rapid enrollment further validates the strong interest from physicians and patients, and highlights the significant unmet need in these patients, who historically have faced a poor prognosis."
Additional Trials
The darovasertib and crizotinib combination is also being evaluated in a Phase 2 trial (NCT03947385). Furthermore, darovasertib is being investigated as a neoadjuvant monotherapy in a Phase 2 trial for primary uveal melanoma (NCT05907954). IDEAYA is also planning to initiate a Phase 3 registration-enabling study for neoadjuvant uveal melanoma patients in the first half of 2025.
