SOUTH SAN FRANCISCO, Calif., June 15, 2026
IDEAYA Biosciences has announced the initiation of a Phase 1/2 clinical combination study evaluating IDE892, a potential best-in-class MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted pancreatic cancer and non-small cell lung cancer (NSCLC). The milestone was marked by the enrollment of the first patient in a trial combining IDE892 with IDE397, the company’s MAT2A inhibitor, targeting a genetically defined patient population with significant unmet medical needs. The study represents a major advancement in IDEAYA’s precision oncology strategy and highlights growing efforts to develop targeted therapies for cancers driven by MTAP deletion, one of the most common genetic alterations across solid tumors.
Novel Precision Oncology Strategy Targets MTAP-Deleted Tumors
The new clinical program is based on a synthetic lethality approach designed to exploit vulnerabilities created by the loss of the MTAP (Methylthioadenosine Phosphorylase) gene. MTAP deletion leads to the accumulation of methylthioadenosine (MTA) and increases tumor dependence on the enzymes PRMT5 and MAT2A, making them attractive therapeutic targets. IDEAYA reported that preclinical studies demonstrated that dual inhibition of PRMT5 and MAT2A using the combination of IDE892 and IDE397 generated potent anti-tumor activity, including complete and durable responses in MTAP-deleted cancer models at doses below those required for monotherapy activity. The company estimates that MTAP deletion occurs in approximately 15% of all solid tumors, including up to 40% of pancreatic cancers and 15–20% of NSCLC cases, highlighting a substantial patient population that currently lacks approved targeted treatment options.
IDE892 Designed as a Potential Best-in-Class PRMT5 Inhibitor
According to IDEAYA Biosciences, IDE892 was engineered with properties intended to support its potential as a best-in-class therapeutic candidate. The molecule demonstrated approximately 1,400-fold selective MTA-PRMT5 cooperative binding compared with SAM-PRMT5 cooperative binding, a characteristic designed to maximize therapeutic selectivity and improve the treatment window. Additionally, IDE892 exhibited favorable drug-like properties in preclinical evaluations, including a low potential for cytochrome P450-mediated drug interactions, an important consideration for combination treatment strategies.
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The ongoing monotherapy Phase 1 dose-escalation study has successfully cleared multiple dose cohorts, with the company reporting that maximally efficacious target exposures are anticipated at a favorable pill size and the maximum tolerated dose has not yet been reached. IDEAYA expects to initiate monotherapy expansion cohorts during the third quarter of 2026, further supporting the program’s clinical development trajectory.
Expanding Combination Approaches in Pancreatic and Lung Cancer
The Phase 1/2 study reflects IDEAYA’s broader vision of developing rational combination therapies capable of producing deeper and more durable responses in genetically defined cancers. Beyond the IDE892 and IDE397 combination, the company has entered a clinical collaboration with Roche to evaluate IDE892 alongside RG6505, Roche’s investigational pan-RAS inhibitor, in MTAP-deleted pancreatic ductal adenocarcinoma (PDAC). This strategy aims to address the frequent co-occurrence of MTAP and KRAS alterations, a molecular profile associated with aggressive disease biology and limited treatment options.
IDEAYA is also advancing an additional proprietary program targeting CDKN2A, another commonly co-altered gene in MTAP-deleted tumors, with an Investigational New Drug application planned for the first half of 2027. As precision medicine continues to reshape oncology treatment paradigms, the launch of the IDE892 combination trial underscores IDEAYA’s commitment to developing innovative therapies for biomarker-defined cancers and addressing critical gaps in care for patients with difficult-to-treat solid tumors.
Source: IDEAYA Biosciences press release
