IDEAYA Biosciences and Servier File NDA Under RTOR for Darovasertib Combination in Metastatic Uveal Melanoma

An NDA filing under FDA's Real-Time Oncology Review (RTOR) program is now in process for the darovasertib-crizotinib combination, with IDEAYA Biosciences and Servier targeting completion in H2 2026, a timeline regulatory affairs teams should map against their own accelerated approval submissions in precision oncology.

Complete data from the registrational Phase 2/3 OptimUM-02 trial, presented as a late-breaking oral at the 2026 ASCO Annual Meeting, showed the combination met its primary endpoint with a statistically significant improvement in median progression-free survival (PFS) by blinded independent central review (BICR): 6.9 months versus 3.1 months against investigator's choice of therapy (ICT), representing a 58% reduction in risk of disease progression (HR: 0.42; 95% CI: 0.30, 0.59; p<0.0001). The trial enrolled 313 patients with first-line HLA*A2:01 negative metastatic uveal melanoma, randomized 2:1 to the darovasertib combination or ICT, where approximately 77% of the control arm received ipilimumab plus nivolumab.

Secondary endpoints reinforced the primary read. Objective response rate (ORR) by BICR reached 37.1% versus 5.8% for ICT, and disease control rate (DCR) was 73.3% versus 31.1%. Investigator-assessed PFS tracked closely with BICR findings: 6.7 months versus 2.7 months (HR: 0.36; p<0.0001), a 64% risk reduction. Overall survival data remain immature, with an early trend favoring the combination; a pre-specified interim analysis will provide the next OS update.

For QA and manufacturing leads preparing for a potential commercial launch, the safety profile warrants close attention. Treatment-related serious adverse events (TR-SAEs) occurred in 9.2% of patients. Discontinuation rates due to treatment-related adverse events were 2.5% for darovasertib and 10% for crizotinib, figures that will inform risk management planning and labeling negotiations with 21 CFR Part 312 obligations in view. The manageable profile was described as consistent with prior trial results, reducing the likelihood of late-stage safety surprises during NDA review.

The RTOR pathway, designed to allow FDA rolling review of completed sections before formal submission, compresses the standard review clock for oncology products with preliminary evidence of substantial improvement. For regulatory affairs leads, the OptimUM-02 package, built on BICR-assessed PFS as the accelerated approval endpoint, illustrates how sponsors are structuring precision oncology dossiers to qualify for RTOR without waiting for OS maturity.

The NDA filing completion in H2 2026 will mark the next measurable checkpoint for this program, with the pre-specified OS interim analysis serving as the confirmatory data anchor that will ultimately determine the path to full approval.

Source: IDEAYA Biosciences newsroom via PR Newswire, June 1, 2026. Data presented at the 2026 ASCO Annual Meeting, Chicago, Illinois; data cutoff January 23, 2026.