IDEAYA and Genentech will evaluate IDE892 with KRAS G12D inhibitor GDC-7035 in MTAP-deleted, KRAS G12D-mutant pancreatic cancer.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
IDEAYA Biosciences has entered into a clinical collaboration with Genentech, a member of the Roche Group, to evaluate IDE892, its investigational MTA-cooperative PRMT5 inhibitor, in combination with GDC-7035 (RG6620), Genentech’s KRAS G12D inhibitor, in patients with pancreatic ductal adenocarcinoma (PDAC) harboring both MTAP deletion and a KRAS G12D mutation.
Under the collaboration, Genentech will sponsor the clinical combination study, while IDEAYA will supply IDE892. The companies will jointly oversee the collaboration through a shared governance structure.
Targeting MTAP-Deleted, KRAS G12D-Mutant PDAC
The collaboration focuses on a molecularly defined subgroup of PDAC in which MTAP deletion and KRAS G12D mutations occur together. IDEAYA estimates that these alterations co-occur in up to approximately 15% of patients with PDAC.
Patients with tumors carrying both alterations currently have no approved targeted treatment options. IDEAYA stated that combining a PRMT5 inhibitor with a KRAS G12D-specific inhibitor may have the potential to produce deeper and more durable responses in this genetically defined patient population.
The new combination therefore brings together two targeted investigational approaches designed to address distinct molecular features of these tumors.
IDE892 Development Program Expands
IDEAYA is currently evaluating IDE892 in a Phase 1 study of monotherapy and combination therapy in patients with MTAP-deleted advanced solid tumors (NCT07277413). The company has also initiated a Phase 1 combination cohort evaluating IDE892 with IDE397, its proprietary MAT2A inhibitor, in non-small cell lung cancer and other solid tumors.
IDEAYA plans to initiate another Phase 1 combination cohort with Roche’s RG6505 in MTAP-deleted, RAS-mutant PDAC during the second half of 2026. The newly announced collaboration adds GDC-7035 as an additional KRAS-directed combination partner within the broader IDE892 development program.
According to IDEAYA, the company is pursuing multiple combination strategies for IDE892, including combinations with IDE397, pan-RAS inhibitors, KRAS-mutant-specific therapies, and its lead CDKN2A compound.
IDE892 Shows Potential Best-in-Class Characteristics
IDEAYA reported that IDE892 has approximately 1,400-fold selective MTA-PRMT5 cooperative binding compared with SAM-PRMT5 cooperative binding. The company also reported that IDE892 was designed to lack brain penetration, with the aim of maximizing its therapeutic window.
These properties are intended to support the development of IDE892 in combination with other targeted therapies, including MAT2A inhibitors, pan-RAS inhibitors, KRAS-directed therapies, and CDKN2A-directed approaches.
IDEAYA also reported that IDE892 has a CYP3A4 IC50 greater than 45 micromolar and did not demonstrate time-dependent inhibition across the seven major cytochrome P450 enzymes: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The findings were based on full kinetic CYP inactivation assays.
According to IDEAYA, these drug-interaction characteristics may further support the development of IDE892 as a combination partner for targeted therapies.
Terms of the Collaboration
Under the clinical collaboration, IDEAYA and Genentech will each retain all commercial rights to their respective compounds, including their use as monotherapies and in combination regimens.
Genentech will sponsor the clinical combination study, while IDEAYA will provide IDE892. The companies will maintain joint governance over the clinical supply collaboration and conduct of the study.
Clinical Significance
The collaboration will evaluate IDE892 in combination with Genentech’s KRAS G12D inhibitor GDC-7035 within Genentech’s Phase I/II clinical program (NCT06619587), which is evaluating GDC-7035 as a single agent and in combination with other anticancer therapies in patients with KRAS G12D-mutant advanced solid tumors. The new collaboration will specifically assess the combination in patients with PDAC harboring both MTAP deletion and a KRAS G12D mutation.
The agreement also expands IDEAYA’s strategy of evaluating IDE892 across multiple rational combination approaches in molecularly selected cancers.
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About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.