IDEAYA Biosciences (NASDAQ:IDYA) outlined upcoming clinical milestones for its precision oncology pipeline, emphasizing an imminent top-line readout in first-line metastatic uveal melanoma (MUM), continued advancement of its antibody-drug conjugate (ADC) portfolio, and the early clinical launch of a KAT6/7 program that management described as a potentially broad opportunity across several solid tumors.
Darovasertib franchise: near-term Phase III PFS readout in metastatic uveal melanoma
The company said its most advanced program, darovasertib, is being evaluated in two randomized Phase III studies, with top-line results expected in “the next couple of weeks,” guided for around the end of March. The upcoming update is focused on the first-line metastatic uveal melanoma setting, where the primary endpoint is median progression-free survival (PFS) assessed by blinded independent central review (BICR).
Study design details and what investors should watch
Company representatives reiterated that the metastatic uveal melanoma Phase III compares an investigator’s-choice standard-of-care control arm (checkpoint inhibitors and, in a small subset, chemotherapy) against the darovasertib + crizotinib combination. Eligible patients are HLA-A2 negative, which management said represents about two-thirds of uveal melanoma patients.
Executives said the current readout is the first “top-line” look at PFS and that there have been no interim looks disclosed prior to this analysis. They also stated that the required 130 PFS events have occurred and that the company is now in the data-cleaning and database lock process ahead of reporting results.
On sample size, the company clarified several components of the broader study framework:
- Phase IIa (dose optimization): 124 patients, with approximately 75 treated at a dose not selected to move forward.
- Move-forward dose and control from Phase IIa: 49 patients.
- Combined Phase IIb/Phase III (intent-to-treat for PFS and OS): 313 patients, which management said reflects rapid enrollment and a “collapsed” Phase IIb/III structure.
Management added that overall survival (OS) may be immature at the time of the PFS readout, and noted the first formal interim OS analysis is expected in the beginning or first half of next year. The trial does not permit crossover until OS reads out, which the company said is an important consideration given limited options for HLA-A2 negative metastatic uveal melanoma.
Mechanism and combination rationale; safety expectations
Executives described darovasertib’s role as targeting Protein Kinase C signaling in uveal melanoma, noting that ~95% of tumors have mutations in GNAQ or GNA11 that drive this pathway. On the combination, the company said crizotinib has limited activity on its own in this disease setting, but that the dual pathway approach (PKC and cMET) has shown enhanced anti-tumor activity preclinically and clinically.
On safety, the company said investigators have gained experience managing adverse events from the combination and expects a safety profile “relatively similar” to what has been seen previously. Management suggested dose management often involves brief pauses or lowering crizotinib (rather than darovasertib) and stated it has observed toxicity tending to occur mainly in the first two months of therapy, with improved tolerability thereafter. The company said it anticipates a relatively low discontinuation rate due to adverse events as clinicians become more adept at managing side effects.
Regulatory and commercial framing; broader label aspirations
IDEAYA said it anticipates approximately six months to prepare a regulatory submission package after top-line data, with an additional ~six months for FDA review as a general guidepost, while aiming to expedite where possible. Management linked that timeline to an expected approval timeframe in the first half of 2027.
In terms of market size, the company estimated 4,000–5,000 incident metastatic uveal melanoma patients globally (concentrated in the U.S., Europe, and Australia), including roughly 1,500 per year in the U.S.
The company also discussed a strategy to support use beyond HLA-A2 negative patients by presenting data in HLA-A2 positive metastatic uveal melanoma from its OptimUM-01 program, aiming for a dataset of nearly 100 patients. Management said it intends to share that package with FDA and the NCCN guidelines panel, arguing there is no mechanistic reason for different drug behavior based on HLA-A2 status.
Pipeline updates: DLL3 Topo ADC, MTAP programs, and KAT6/7 enters Phase I
Beyond darovasertib, IDEAYA highlighted three additional areas of focus:
- DLL3 Topo ADC (IDE-849): Management guided to a clinical data update by year-end for monotherapy, said enrollment is picking up outside of Asia, and described the molecule as having “potential to be a best-in-class asset.” The company referenced previously presented single-agent activity at the World Conference on Lung Cancer in September (as an oral presentation).
- MTAP deletion portfolio: IDEAYA said it has two clinical assets in this area—PRMT5 and MAT2A—with opportunities in monotherapy and combinations, and noted “interesting intersections” between RAS and MTAP biology. Management also referenced guidance for an MTAP clinical data update with Trodelvy.
- KAT6/7 (IDE-574): The company said IDE-574 has entered Phase I and positioned it as a “unique opportunity” with potentially large addressable populations, including breast cancer and colorectal cancer. Chief Scientific Officer Mick White emphasized the importance of dual potency on KAT6 and KAT7, arguing KAT7 can compensate for KAT6A/6B and may play a role in intercepting both intrinsic and acquired resistance mechanisms, including drug-tolerant persister cells and tumor-initiating progenitor-like cells.
IDEAYA also said it plans to initiate a PARP inhibitor combination with its DLL3 Topo ADC soon (management indicated dosing could begin in roughly about a month) and suggested early signals such as response rate and pharmacodynamic readouts could emerge before longer durability follow-up is available.
About IDEAYA Biosciences (NASDAQ:IDYA)
IDEAYA Biosciences is a clinical-stage precision oncology company dedicated to the discovery and development of novel therapies that exploit synthetic lethality in cancer cells. By targeting key DNA damage response pathways, the company aims to selectively kill tumor cells exhibiting specific genetic vulnerabilities while sparing healthy tissue. IDEAYA’s pipeline includes small-molecule inhibitors designed to address underserved tumor types, and its lead programs are advancing through Phase 1 and Phase 2 clinical trials in multiple oncology indications.
Central to IDEAYA’s approach is its Modular Approach to Precision (MAP) platform, which integrates proprietary genomic and functional screening technologies to identify critical cancer-specific dependencies.
