IDEAYA Biosciences Spotlights Darovasertib Win, FDA Review Path at Oncology Summit

Key Points

• Darovasertib plus crizotinib hit its primary endpoint in a registrational Phase II/III study for metastatic uveal melanoma, with a progression-free survival hazard ratio of 0.42 and median PFS of 6.9 months versus 3.1 months for control. IDEAYA said the data support an accelerated approval path and that the FDA has granted Real-Time Oncology Review and Fast Track status.
• IDEAYA is planning broader FDA/NDA submission steps, including staggered filing of HLA-A*02-positive data, while it also has plans for label expansion and guideline uptake based on a larger patient dataset. The company said it expects expedited review could shave months off the timeline.
• Beyond darovasertib, IDEAYA highlighted several earlier-stage pipeline programs, including the DLL3-targeted ADC IDE849, the B7-H3/PTK7 bispecific ADC IDE034, and synthetic lethality assets in MTAP-deletion, CDKN2A, and KAT6/7. Management said these programs could support significant long-term growth across multiple cancer types.

IDEAYA Biosciences NASDAQ: IDYA executives highlighted recent clinical progress across the company’s oncology pipeline during a fireside chat at TD Cowen’s seventh annual Oncology Innovation Summit, with the discussion focused primarily on darovasertib combinations in uveal melanoma and several earlier-stage antibody-drug conjugate and synthetic lethality programs.

Yujiro Hata, IDEAYA’s chief executive officer, said the company’s randomized registrational Phase II/III study of darovasertib plus crizotinib, referred to during the discussion as darocriz, in HLA-A*02-negative frontline metastatic uveal melanoma met its primary endpoint for accelerated approval. The study is evaluating median progression-free survival for accelerated approval and overall survival for full approval.

Hata said the trial showed a progression-free survival hazard ratio of 0.42 with a p-value of less than 0.0001. Median progression-free survival was 6.9 months in the treatment arm compared with 3.1 months in the control arm, which he said was largely ipilimumab plus nivolumab. He said the control-arm result was in line with the company’s expectations.

Hata also pointed to response-rate data, saying the treatment arm was “trending towards 40% confirmed response rate” by central review, while the control arm came in at a single-digit percentage. IDEAYA plans to present fuller results in a late-breaker oral presentation on Monday, June 1, including CT scan waterfall plots for both treatment and control arms by independent central review and investigator assessment, as well as full safety adverse-event tables.

Overall Survival and Regulatory Plans

Asked about confidence in ultimately showing an overall survival benefit, Hata said IDEAYA has “quite a bit of confidence,” citing the response-rate separation, the more than doubling of progression-free survival and previously reported survival data. He said the company reported overall survival of just over 21 months last fall across HLA-A*02-negative and positive frontline patients, compared with a referenced ipilimumab/nivolumab study in which overall survival was 12.5 months.

Hata said IDEAYA also has a sizable HLA-A*02-positive data set that has been submitted for presentation at a major medical conference. That data set is expected to include roughly 100 patients and report response rate, progression-free survival and overall survival, including a treatment-naive subset.

For HLA-A*02-positive patients, Hata said the company views inclusion on the label as “potential upside” rather than its base case. He said IDEAYA plans to submit the data as part of its New Drug Application, while its base-case strategy would be to pursue compendia and NCCN guideline inclusion based on the approximately 100-patient data set.

Hata said IDEAYA has had discussions with the U.S. Food and Drug Administration regarding HLA-A*02-negative and positive populations, but did not provide specifics. He added that IDEAYA recently received Real-Time Oncology Review from the FDA’s Oncology Center of Excellence, allowing the NDA to be submitted through three pre-submission modules. He said the first module has already been submitted, and the HLA-A*02-positive data are expected to follow as a staggered submission.

IDEAYA also has Fast Track designation for the program, and Hata said the company anticipates expedited review. He said RTOR could potentially shorten the review process by “even a few months” in certain cases, depending on the program.

Expansion Into Earlier Uveal Melanoma Settings

IDEAYA also discussed darovasertib monotherapy in the neoadjuvant uveal melanoma setting through the single-arm Phase II OptimUM-09 study. Hata said updated data expected in the second half of the year should include more patients, longer follow-up and additional analyses for both the enucleation cohort and plaque therapy cohort. He noted that the program received FDA Breakthrough Therapy designation in the indication last spring.

In the adjuvant setting, Hata said IDEAYA is pursuing a study aligned with its strategy to move precision oncology therapies into earlier-stage disease. The company and its partner Servier are working on a trial with approximately 450 patients randomized one-to-one against observation, with 12 months of treatment and relapse-free survival as the primary endpoint. Hata said the study will be HLA agnostic and that the readout is likely to mature in about three to three-and-a-half years.

On commercial opportunity, an IDEAYA representative said the company sees a “credible path” for darovasertib plus crizotinib to become a blockbuster across uveal melanoma, potentially reaching a multi-billion-dollar opportunity if the drug succeeds across metastatic, primary and adjuvant settings. The representative said pricing, duration of therapy, penetration into HLA-A*02-positive patients and use in earlier settings would be key drivers.

ADC Programs in DLL3 and Bispecific Targeting

IDEAYA also reviewed its antibody-drug conjugate pipeline, including IDE849, a DLL3-targeted ADC for small cell lung cancer and neuroendocrine carcinoma. Hata said IDEAYA views DLL3 as the most optimal target in small cell lung cancer among several antigens being pursued, comparing its role in the ADC landscape to HER2 in breast cancer.

Hata said IDE849 uses a tetrapeptide cleavable linker that is designed to cleave only after internalization, which IDEAYA believes could provide a safety advantage over tumor microenvironment-cleavable linkers. He said partner Hengrui Pharma is expanding at 2.4 mg/kg, and IDEAYA is targeting higher doses in expansion outside China as well.

The company expects two data sets later this year: more than 100 patients across small cell lung cancer and neuroendocrine carcinoma, including response rate, progression-free survival and first-time 12-month landmark overall survival data; and likely more than 30 patients from the U.S., Europe and other parts of Asia. Hata said IDEAYA believes IDE849 could be a potential best-in-class asset across DLL3 modalities.

Michael White, IDEAYA’s chief scientific officer, also discussed IDE034, the company’s B7-H3/PTK7 bispecific ADC. White said the bispecific design is intended to bind and internalize more effectively in double-positive tumor cells than in single-positive cells, potentially improving delivery of the payload to tumors while reducing normal-tissue internalization. Hata said early monotherapy data expected in the second half will be “fairly early” and may include response-rate information, with emphasis on solid tumors such as colorectal cancer and non-small cell lung cancer.

Synthetic Lethality and KAT6/7 Programs

On IDEAYA’s MTAP-deletion strategy, Hata said the company considers itself one of the industry leaders, with two clinical-stage assets targeting independent pathways and a third program around CDKN2A moving toward the clinic, targeted for the first half of next year. He said IDEAYA’s strategy includes fully suppressing the PRMT5 pathway by targeting both MAT2A and PRMT5, with a focus on non-small cell lung cancer, and pursuing co-alteration strategies including CDKN2A and RAS mutations in pancreatic and colorectal cancers.

White said CDKN2A deficiency occurs at higher frequency than MTAP deletion in pancreatic cancer and often co-occurs with KRAS. He said IDEAYA has preclinical evidence supporting activity in pancreatic tumor settings, both as monotherapy for CDKN2A deficiency and in combinations targeting co-alterations.

White also described IDEAYA’s KAT6/7 dual inhibitor program, saying the company believes inhibiting KAT6 alone is insufficient because KAT7 also contributes to oncogenic chromatin regulation. He said the company is studying the asset in dose-escalation trials in lung cancer, colorectal cancer, hormone-positive breast cancer and prostate cancer. White added that IDEAYA has observed preclinical synergy with RAS inhibitors, particularly relevant to colorectal cancer, where KRAS mutations, heterogeneity and adaptive resistance are common challenges.

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.

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