IDEAYA Biosciences (NASDAQ:IDYA) executives outlined multiple upcoming clinical catalysts at Citi’s 2026 Virtual Oncology Leadership Summit, led by an end-of-March top-line readout for the company’s randomized trial of darovasertib plus crizotinib in metastatic uveal melanoma (MUM). Management also discussed ongoing expansion of darovasertib into earlier-stage uveal melanoma settings, initial enrollment progress across several antibody-drug conjugate (ADC) programs, and next steps in the company’s MTAP-focused combination strategy.
Near-term focus: darovasertib + crizotinib top-line data in metastatic uveal melanoma
Chief Financial Officer Joshua Bleharski said IDEAYA has triggered the 130 events required for the top-line analysis of darovasertib plus crizotinib in metastatic uveal melanoma and expects to release those results at the end of March. Chief Medical Officer Darrin Beaupre described the study as a randomized comparison in metastatic uveal melanoma patients who are HLA-A2 negative, with the control arm reflecting standard-of-care treatments that vary by region.
In discussing expectations for the control arm, Beaupre cited two large meta-analyses that the company has referenced previously, stating that standard of care has generally produced median progression-free survival (PFS) of about 2–3 months and overall survival (OS) around 13 months. He contrasted that with previously presented IDEAYA data for darovasertib plus crizotinib in first-line patients, noting a median PFS of about 7 months and median OS of about 21 months, along with an overall response rate (ORR) above 30% versus approximately 10% for standard of care.
Beaupre also discussed how scan frequency could influence apparent PFS, noting patients in the randomized study are scanned every six weeks and arguing this could lead to earlier detection of progression versus studies with less frequent imaging. He emphasized that investors should focus on the hazard ratio comparing the two arms. He added that the trial does not allow crossover in order to preserve OS interpretability, but said the company would need to consider the ethical implications if OS trends strongly favor the experimental arm as data mature.
What the company expects to report and how OS may be handled
Beaupre said the top-line disclosure is expected to include metrics such as ORR for the treatment and control arms, durability (including duration of response), and PFS (potentially with confidence intervals). He cautioned that if the company does not provide OS at top line, it should not be interpreted as a negative signal, but rather as potentially reflecting an insufficient number of events to make a call.
He noted a formal OS interim analysis is planned for the beginning of 2027. In the discussion, Beaupre suggested that around 30% of OS events is a threshold at which stakeholders may begin to have more confidence in OS trends, while fewer events may limit interpretability.
Regulatory timing and plans for HLA-A2 positive patients
On potential filing timelines following a positive result, Beaupre said a standard approach would be roughly six months to file, followed by at least six months of FDA review, while adding that IDEAYA will try to compress timelines where possible.
He also highlighted plans for HLA-A2 positive metastatic uveal melanoma patients. Beaupre said the “biology says there shouldn’t be any difference” in activity by HLA-A2 status and referenced data presented at ESMO 2023 indicating HLA-A2 positive patients behaved similarly to HLA-A2 negative patients when treated with the darovasertib combination. He said the company’s phase 2 dataset is evolving toward about 100 HLA-A2 positive patients, including a significant proportion expected to have been exposed to tebentafusp.
Beaupre outlined a plan to present the HLA-A2 positive dataset in “two chapters” over the next year, with an initial subset potentially providing ORR, PFS, and possibly OS depending on data maturity, followed by publication of the full dataset around the time of filing or approval. He said IDEAYA intends to provide the data to NCCN for guideline consideration and is also discussing with the FDA whether and how HLA-A2 positive data could potentially be reflected on the label, noting the orphan nature of the indication and unmet need.
Earlier-stage uveal melanoma: neoadjuvant and adjuvant expansion
Beyond metastatic disease, management described ongoing efforts to move darovasertib into neoadjuvant and adjuvant uveal melanoma settings. Bleharski said IDEAYA is already enrolling in a neoadjuvant study and expects to begin enrolling an adjuvant study in the second quarter.
Beaupre said the neoadjuvant registration trial uses single-agent darovasertib in primary uveal melanoma with two cohorts:
- Large tumors destined for enucleation, where the primary endpoint is saving the eye
- Smaller to mid-sized tumors treated with plaque brachytherapy, where the primary endpoint is preservation of vision
He added that event-free survival is an important endpoint in both cohorts, intended to show that delaying local therapy for neoadjuvant treatment does not create a detriment in local or distant relapse. Beaupre estimated enrollment could take about a year to a year and a half, with readouts about a year and a half after primary local therapy; he also suggested the enucleation cohort could read out earlier than the plaque brachytherapy cohort.
For the adjuvant setting, Beaupre said IDEAYA is preparing for an FDA Type C meeting and plans to launch the randomized study by mid-year. He described a design enrolling high-risk patients randomized to observation (current standard practice) versus darovasertib for up to one year, with the goal of reducing downstream metastases.
Pipeline updates: DLL3 ADC, bispecific ADC strategy, and MTAP combinations
Bleharski said IDEAYA has about nine programs in the clinic, and ended the quarter with about $1.05 billion in cash, with runway into 2030.
On the DLL3 topoisomerase-1 (TOPO1) ADC, Beaupre said the U.S. phase 1 has launched and is enrolling. He referenced data “from China” presented at the World Lung Conference that showed a high response rate (70%) and early PFS of “six months or better.” For IDEAYA’s U.S. effort, he said the company expects an initial phase 1 data update by the end of the year and also plans to initiate a registrational monotherapy study in later-line small cell lung cancer or neuroendocrine carcinoma by year-end.
Chief Scientific Officer Michael White discussed the rationale for combining TOPO1 ADC payloads with IDEAYA’s PARG inhibitor (IDE161), describing PARG as essential to resolving topoisomerase-1 cleavage complexes and framing the combination as a strategy to enhance durability by amplifying DNA damage effects.
White also described the company’s bispecific PTK7/B7-H3 TOPO1 ADC (IDE034), which Bleharski said is entering phase 1. White said the bispecific approach is designed to enhance binding to tumors that are double-positive for B7-H3 and PTK7 while limiting binding to normal tissues, citing endometrial tissue as the only normal tissue where the company is seeing double positivity. He said IDEAYA expects to explore IDE034 both as monotherapy and in combination with IDE161 to maximize payload impact.
In the MTAP space, Bleharski highlighted IDE397, a MAT2A inhibitor being explored in combination with Trodelvy in MTAP-deleted urothelial cancer, with an update expected in 2026 at a medical meeting. Beaupre said the dataset has grown since prior disclosures, and he characterized the response rate and durability as promising, arguing the combination is “clearly doing better than Trodelvy could do” alone in that population, while lung cancer expansion remains earlier and still evolving. White described the combination as increasing damage while reducing repair capacity, and said IDEAYA sees broader potential to pair MAT2A inhibition with other TOPO1 payload ADCs.
White also discussed a separate MTAP strategy involving a PRMT5 inhibitor combination (referencing IDE892 in the discussion), describing it as a different mechanistic thesis aimed at improving depth and durability of response by intercepting adaptive resistance mechanisms and optimizing the MTA/SAM ratio underlying synthetic lethality in MTAP-loss tumors. He further described interest in leveraging the frequent co-loss of CDKN2A with MTAP loss at 9p21.3 and noted the company has considered how that co-alteration could be attacked in combination approaches, including in pancreatic cancer where KRAS alterations are common.
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.
