A Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of IDE892 as Monotherapy and Combination Therapy in Participants With MTAP-Deleted Advanced Solid Tumors

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Trial Details

Sponsor: IDEAYA Biosciences (industry)

Phase: 1

Start date: Dec. 11, 2025

Planned enrollment: 260

Trial ID: NCT07277413
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More trial details at ClinicalTrials.gov More info

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Goal: To define the safety profile, dose-limiting toxicities, and recommended dose(s) of IDE892 given alone and with the MAT2A inhibitor IDE397, and to characterize pharmacokinetics/pharmacodynamics and preliminary antitumor activity in MTAP-deleted advanced solid tumors, with expansion focused on MTAP-deleted NSCLC after standard therapies.

Patients: Adults (≥18 years) with locally advanced recurrent or metastatic solid tumors with centrally confirmed MTAP homozygous loss/deletion, ECOG 0–1, measurable disease by RECIST 1.1, adequate organ function, and life expectancy >3 months. Dose-escalation cohorts include mesothelioma (pleural/peritoneal), gastroesophageal cancers, NSCLC, and urothelial cancer after progression on standard therapy. Dose-expansion cohorts are restricted to MTAP-deleted NSCLC that has progressed after platinum chemotherapy and PD-1/PD-L1 therapy (unless contraindicated/intolerant), with no more than 3 prior lines total (≤2 chemotherapy lines), and prior appropriate targeted therapy if a standard actionable alteration is present.

Design: Multicenter, open-label, non-randomized Phase 1 study with four parts: IDE892 monotherapy dose escalation using a Bayesian Optimal Interval design; IDE892 monotherapy NSCLC dose expansion; IDE892+IDE397 combination dose escalation using a modified toxicity probability interval design; and IDE892+IDE397 combination NSCLC dose expansion. Treatment is administered in 21-day cycles, with escalation to establish MTD and/or recommended dose(s) for expansion and evaluation of preliminary efficacy in expansion cohorts.

Treatments: IDE892 is administered as monotherapy and in combination with IDE397. IDE892 is an investigational small-molecule, MTA-cooperative inhibitor of PRMT5 intended to exploit the elevated methylthioadenosine milieu in MTAP-deleted tumors to increase tumor selectivity of PRMT5 inhibition; as of the current study stage, peer-reviewed human efficacy and detailed safety results for IDE892 have not been reported. IDE397 is an oral MAT2A inhibitor designed to reduce SAM production and deepen the methylation stress created by MTAP loss; it is included to potentially enhance therapeutic index and antitumor activity when paired with PRMT5 inhibition. The combination strategy aims to intensify the MTAP-deletion–associated methylation vulnerability through dual targeting of PRMT5 and MAT2A.

Outcomes: Primary endpoints are dose-limiting toxicities during the first 21 days of IDE892 exposure in the escalation parts (monotherapy and combination), overall incidence and severity of AEs/SAEs graded by CTCAE v5.0 across all parts, and investigator-assessed objective response rate and duration of response by RECIST 1.1 in the NSCLC expansion parts. Secondary endpoints include ORR and DOR in the escalation parts, disease control rate and duration of stable disease across all parts, and extensive IDE892 pharmacokinetic parameters (including Cmax, Tmax, AUClast, AUCinf, half-life, steady-state measures, clearance, volume of distribution, and accumulation) assessed primarily on Cycle 1 Day 1 and Day 15.

Burden on patient: High. This is an early-phase, multi-part dose-escalation/expansion study that requires archival tumor submission for central MTAP confirmation and mandates serial blood sampling for biomarkers and intensive pharmacokinetic profiling, with multiple PK time points concentrated around Cycle 1 Day 1 and Day 15. Patients can expect frequent clinic visits early in therapy for safety monitoring and DLT assessment, along with routine imaging for RECIST-based response assessment over time, and potential added travel burden typical of multicenter Phase 1 trials that often concentrate at specialized sites.

Last updated: Feb 2026

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NEXT Oncology Dallas

Irving, Texas, 75039, United States

[email protected] / 972-893-8800

Status: Recruiting

NEXT Oncology Houston

Houston, Texas, 77054, United States

[email protected] / 832-384-7912

Status: Recruiting

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

[email protected] / 703-783-4518

Status: Recruiting

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