IDEAYA Biosciences Submits NDA for Darovasertib Combination in Metastatic Uveal Melanoma

IDEAYA Biosciences has completed its first NDA submission to the FDA for darovasertib plus crizotinib in metastatic uveal melanoma, triggering the agency's Real-Time Oncology Review (RTOR) pathway, a filing sequence that compresses standard review timelines and places immediate pressure on CMC documentation, labeling readiness, and manufacturing site qualification.

The submission, completed in Q3 2026, follows positive topline data from the OptimUM-02 trial demonstrating a statistically significant improvement in median progression-free survival versus investigator's choice of therapy in treatment-naive HLA-A*02:01-negative patients, confirmed by blinded independent central review. OptimUM-01 data in 101 HLA-A*02:01-positive patients, spanning treatment-naive and second-line settings, further supports a broad label claim irrespective of allele status or line of therapy. For regulatory affairs leads, the breadth of the clinical dataset across patient subgroups will be a focal point during FDA review, particularly around subgroup consistency and the adequacy of the comparator arm.

The combination involves a PKC inhibitor (darovasertib) paired with crizotinib, an established MET/ALK inhibitor with a known formulation and manufacturing profile. QA and CMC teams will need to ensure that drug-drug interaction data, stability packages, and any co-administration device or packaging configurations are fully aligned with 21 CFR Part 211 requirements before a potential approval action. RTOR's iterative review model means rolling deficiency letters are possible well ahead of the PDUFA date, compressing response windows for manufacturing and quality teams.

In parallel, IDEAYA reported Phase 2 neoadjuvant data from OptimUM-09 in primary uveal melanoma: more than 85% of approximately 119 enrolled patients experienced tumor shrinkage, with a 57% eye preservation rate in the enucleation cohort. While this indication is not part of the current NDA, the dataset positions darovasertib for potential label expansion discussions and adds to the regulatory dossier that inspectors and reviewers will assess for benefit-risk consistency.

On the pipeline side, updated data for IDE849, a DLL3 TOP1 antibody-drug conjugate, presented at ESMO 2026 showed anti-tumor activity in relapsed small cell lung cancer and neuroendocrine carcinomas from a Hengrui-sponsored Phase 1 trial. IDEAYA's own global Phase 1/2 data for IDE849 is expected by end of 2026 or early 2027, a timeline that will inform whether a second IND-stage CMC package requires parallel resourcing.

IDEAYA reported $1.15 billion in cash, cash equivalents, and marketable securities as of September 30, 2026, with cash runway guidance extending into 2030 under the current operating plan, a position that supports sustained investment in manufacturing scale-up and regulatory operations through a potential commercial launch.

The FDA's action on the darovasertib NDA under RTOR will serve as a near-term indicator of how the agency evaluates combination oncology submissions with broad subgroup claims in rare tumor types.

Source: IDEAYA Biosciences Newsroom via PR Newswire, November 3, 2026.