IDEAYA Starts IDE892 Phase 1/2 Expansion in MTAP-Deleted PDAC and NSCLC

IDEAYA Biosciences has initiated the Part 2 monotherapy expansion of its ongoing Phase 1/2 clinical trial (NCT07277413) evaluating IDE892 in patients with methylthioadenosine phosphorylase (MTAP)-deleted pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). The expansion follows successful dose escalation, where the investigational therapy achieved projected efficacious target exposures with sustained 24-hour target EC90 coverage across multiple dose cohorts. Dose escalation remains ongoing, and the maximum tolerated dose (MTD) has not yet been reached.

IDE892 is a potential best-in-class methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor designed for MTAP-deleted cancers, which currently have no approved targeted therapies. The Part 2 expansion will further evaluate the drug’s safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity in PDAC and NSCLC, two tumor types with among the highest rates of MTAP deletion.

MTAP deletion creates a synthetic lethal therapeutic target

MTAP deletion occurs in approximately 15% of all solid tumors, including 15% to 20% of NSCLC and up to 40% of PDAC. Loss of MTAP results in methylthioadenosine (MTA) accumulation, increasing tumor dependence on PRMT5 and methionine adenosyltransferase 2A (MAT2A), creating a synthetic lethal vulnerability.

IDE892 has been engineered to exploit this biology through approximately 1,400-fold greater cooperative binding selectivity for the MTA-bound PRMT5 complex compared with the S-adenosyl methionine (SAM)-bound complex. The molecule also has limited brain penetration and favorable drug-like properties intended to maximize its therapeutic window for both monotherapy and combination treatment.

Dose-escalation findings support expansion

The ongoing Phase 1/2 study is evaluating IDE892 as both a monotherapy and in combination regimens for MTAP-deleted advanced solid tumors. IDEAYA reported that projected efficacious target exposures were achieved across multiple dose cohorts while maintaining a favorable safety profile. The MTD has not yet been reached, and dose escalation continues alongside the newly initiated expansion cohorts.

Combination strategy targets MTAP co-alterations

IDEAYA is advancing multiple combination strategies to enhance treatment of MTAP-deleted cancers. The company is evaluating IDE892 with IDE397, its investigational MAT2A inhibitor, following first-patient dosing in mid-2026.

In collaboration with Roche, IDEAYA also plans to evaluate IDE892 with RG6505, Roche’s investigational pan-RAS inhibitor, in MTAP-deleted PDAC to target the frequent co-alterations of MTAP and KRAS, with first-patient initiation expected in the second half of 2026.

IDE892 may also be well suited for combination therapy because of its favorable drug interaction profile. The investigational agent demonstrated a CYP3A4 IC50 greater than 45 μM and showed no time-dependent inhibition across the seven major cytochrome P450 enzymes, supporting its potential as a combination partner.

Broader MTAP precision oncology pipeline

IDE892 is part of IDEAYA’s broader MTAP-targeted precision oncology strategy, which also includes the Phase 2 MAT2A inhibitor IDE397 and a proprietary CDKN2A-targeted program currently in preclinical toxicology studies, with an investigational new drug application planned for the first half of 2027. Because CDKN2A deficiency occurs in approximately 70% of PDAC cases, the company plans to explore future combination strategies targeting multiple genomic co-alterations.

IDEAYA also plans to host an MTAP/CDKN2A, KRAS, and Pancreatic Cancer R&D Day in the fourth quarter of 2026 to outline its combination development strategy and broader MTAP franchise.

With monotherapy expansion underway, ongoing dose escalation, and multiple combination studies advancing, upcoming clinical data are expected to further characterize IDE892’s safety, pharmacologic profile, and clinical potential in MTAP-deleted pancreatic and lung cancers.

Reference

IDEAYA Biosciences Announces IDE892, a Potential Best-in-Class MTA-Cooperative PRMT5 Inhibitor, Initiates Part 2 Monotherapy Expansion in the Phase 1/2 Study in MTAP-Deleted Pancreatic and Lung Cancers – Jul 27, 2026