A Study of IDE892 as Monotherapy and Combination in MTAP-deleted Advanced Solid Tumors

April 2, 2026 updated by: IDEAYA Biosciences

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

This is a multicenter clinical study to evaluate the safety, efficacy, and Pharmacokinetics (PK) of IDE892 as monotherapy and in combination with other agents including IDE397 in participants with methylthioadenosine phosphorylase (MTAP)-deleted advanced solid tumors within indications of interest.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to evaluate safety, efficacy, and PK of IDE892 as monotherapy and combination therapy in adult participants with MTAP-deleted tumors who have progressed after standard therapy and represent a high unmet need. In the current stage, the combination will be focused on IDE892 with IDE397, an oral inhibitor of methionine adenosyltransferase 2A (MAT2A), to fully exploit the vulnerabilities associated with methylthioadenosine (MTA) accumulation in MTAP-deleted tumors while maintaining a substantial therapeutic index. The mechanistic rationale for this study is discussed in the following sections.

Study Type

Interventional

Enrollment (Estimated)

260

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32827
        • Recruiting
        • Sarah Cannon Research Institute at Florida Cancer Specialists
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Nebraska Cancer Specialists
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Sidney Kimmel Comprehensive Cancer Center Thomas Jefferson University
        • Contact:
        • Contact:
          • askphase1@jefferson.edu
          • Phone Number: 215-586-0199
    • Tennessee
      • Nashville, Tennessee, United States, 37203
    • Texas
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson
        • Contact:
      • Houston, Texas, United States, 77054
      • Irving, Texas, United States, 75039
    • Virginia
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Are ≥ 18 years of age at the time of signing the ICF.
  • Have a histologically confirmed diagnosis of a locally advanced recurrent or metastatic solid tumor type of interest with MTAP deletion (for dose escalation: mesothelioma [pleural or peritoneal], gastroesophageal cancers [squamous and adenocarcinoma of esophagus, gastric adenocarcinoma, gastroesophageal junction cancers], NSCLC [adenocarcinoma, squamous cell carcinoma, and adeno-squamous] and UC [including mixed urothelial-squamous histology]; for dose expansion: NSCLC that has progressed on at least one prior line of treatment and for which additional effective standard therapy is not available or for which the participant is not a candidate due to intolerance).
  • Are willing and able to provide blood/tumor tissue samples for biomarker testing. An archival tumor tissue specimen must be provided for central confirmation of MTAP loss.
  • Must be willing and able to provide the blood/serum/plasma samples
  • Have evidence of homozygous loss of MTAP or MTAP deletion (pre-screening available after signing pre-screening ICF)
  • Have at least 1 measurable lesion according to RECIST version 1.1
  • Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1
  • Have life expectancy > 3 months
  • Have adequate bone marrow and organ function
  • Able to retain administered study drug/IMP.
  • Male and female: willing to use contraception

Exclusion Criteria:

  • Known symptomatic brain metastases requiring supraphysiologic doses of systemic corticosteroids
  • Have a known primary central nervous system (CNS) malignancy
  • Have had other malignancies within 2 years prior to the first dose, with some exceptions
  • Impaired cardiac function or clinically significant cardiac diseases
  • Have presence of uncontrolled pleural, peritoneal, or pericardial effusion within 2 weeks before the first study dose, requiring recurrent drainage procedures or an indwelling drainage catheter
  • Have a history of severe infections within 4 weeks prior to the start of study treatment
  • Hypertension (e.g., > 150/100 mmHg) that cannot be controlled by medications despite optimal medical therapy
  • Other acute or chronic medical or psychiatric condition
  • Have a history of immunodeficiency, with a positive human immunodeficiency virus(HIV) test at screening
  • Known or suspected viral hepatitis
  • Had an adverse reaction to a previous antitumor treatment that has not recovered to CTCAE Grade ≤ 1
  • Have received chemotherapy within 3 weeks of the first dose of IMP; immunotherapy or biologic targeted antitumor treatments within 2 weeks before the first dose of IMP; small molecule inhibitors within 2 weeks before the first dose of IMP, or other investigational products within 4 weeks
  • Current radiation-related toxicity or radiation therapy within 2 weeks before the first dose of IMP
  • Administration of any of the following within 2 weeks before the first dose of IDE892 as a monotherapy: Strong inhibitors or inducers of cytochrome P450, Strong inhibitors of P-glycoprotein, Narrow therapeutic index and sensitive substrates of multidrug and toxin extrusion (MATE)1 and MATE2-K, Narrow therapeutic index and sensitive substrates of P-gp and breast cancer resistance protein
  • Administration of any of the following within 2 weeks before the first dose of IDE892: Strong inhibitors or inducers of CYP3A4/5, Strong inhibitors of P-gp and/or BCRP, Narrow therapeutic index and sensitive substrates of MATE1 and MATE2-K, Narrow therapeutic index and sensitive substrates of P-gp and BCRP
  • Use of proton pump inhibitors (PPIs) within 7 days prior to the first dose of IMP or planned use during the study
  • Use of drugs with known risk for QT prolongation within 2 weeks prior to the first dose of IDE892
  • Previous treatment with a MAT2A inhibitor and/or Protein arginine N-methyltransferase (PRMT) inhibitor
  • Major surgery within 4 weeks before study entry
  • Prior irradiation to > 25% of the bone marrow
  • Known or suspected hypersensitivity to IDE892

Disease-Specific Eligibility Criteria NSCLC

  • Must have histologically confirmed diagnosis of advanced or metastatic NSCLC that has progressed after prior treatment with platinum chemotherapy and a PD-1/PD-L1 inhibitor (unless contraindicated or participant developed intolerance) in the metastatic setting
  • Treatment with no more than 3 prior lines, including no more than 2 prior lines of chemotherapy.
  • If considered standard of care and available, participants whose cancers have proven targetable oncogene alterations must have had disease progression on (unless contraindicated or participant developed intolerance) at least 1 prior line containing appropriate targeted therapy.

Urothelial Cancer (Bladder and Upper Urinary Tract), Mesothelioma (Pleural or Peritoneal) and Gastroesophageal Cancers

  • Must have histologically confirmed diagnosis of advanced or metastatic UC, mesothelioma, or gastroesophageal cancer
  • Must have progressed following at least 1 prior line of therapy
  • Treatment with no more than 3 prior lines, including no more than 2 prior lines of chemotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1: IDE892 Monotherapy Dose Escalation (MTAP-deleted advanced solid tumors)
Participants with advanced or metastatic solid tumors harboring MTAP deletion (including mesothelioma, gastroesophageal cancers, non-small cell lung cancer, and urothelial cancer) will receive IDE892. Dose levels will be escalated sequentially using a Bayesian Optimal Interval (BOIN) design to evaluate safety, tolerability, and to determine the maximum tolerated dose and/or recommended dose for expansion. PK and pharmacodynamics (PD) and preliminary antitumor activity will also be assessed.
Drug: IDE892
IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
Experimental: Part 2: IDE892 Monotherapy Dose Expansion (MTAP-Deleted NSCLC)
Participants with advanced or metastatic NSCLC with MTAP deletion will receive IDE892. One or more dose levels at or below the maximum tolerated dose from Part 1 will be further evaluated to determine the recommended Phase 2 dose and to assess antitumor activity.
Drug: IDE892
IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
Experimental: Part 3: IDE892 + IDE397 Combination Dose Escalation (MTAP-Deleted Solid Tumors)
Participants with advanced or metastatic solid tumors harboring MTAP deletion (including mesothelioma, gastroesophageal cancers, non-small cell lung cancer, and urothelial cancer) will receive IDE892 in combination with IDE397. Dose levels will be escalated using a modified toxicity probability interval (mTPI) design to evaluate safety, tolerability, and to determine the maximum tolerated dose and/or recommended dose for expansion. PK, PD, and preliminary antitumor activity will also be assessed.
Drug: IDE892
IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
Drug: IDE397
IDE397 is an oral MAT2A inhibitor that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions. In this study, IDE397 will be evaluated in combination with IDE892 (Parts 3 and 4) in participants with MTAP-deleted advanced solid tumors.
Experimental: Part 4: IDE892 + IDE397 Combination Dose Expansion (MTAP-Deleted NSCLC)
Participants with advanced or metastatic NSCLC with MTAP deletion will receive IDE892 in combination with IDE397. One or more dose levels at or below the maximum tolerated dose from Part 3 will be further evaluated to determine the recommended Phase 2 dose and to assess antitumor activity.
Drug: IDE892
IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
Drug: IDE397
IDE397 is an oral MAT2A inhibitor that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions. In this study, IDE397 will be evaluated in combination with IDE892 (Parts 3 and 4) in participants with MTAP-deleted advanced solid tumors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Parts 2 and 4)
Time Frame: Approximately 2 years
Objective response rate (ORR: best objective response of complete response [CR] + partial response [PR]) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator
Approximately 2 years
Incidence of Dose-limiting Toxicities (DLTs) of IDE892 (Parts 1 and 3)
Time Frame: 21 days following the first dose of IDE892 (each cycle is 21 days)
Incidence of DLTs of IDE892 will be determined in Parts 1 and 3
21 days following the first dose of IDE892 (each cycle is 21 days)
Incidence of AEs and SAEs (Parts 1, 2, 3, and 4)
Time Frame: From first dose until 28 days after last dose (each cycle is 21 days)
Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) (graded based on Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) will be determined in Parts 1, 2, 3, and 4.
From first dose until 28 days after last dose (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR) and duration of response (DOR) per RECIST version 1.1 (Parts 1 and 3)
Time Frame: Approximately 2 years
ORR and DOR per RECIST version 1.1 as assessed by the Investigator
Approximately 2 years
Disease control rate (DCR) and duration of stable disease per RECIST version 1.1 (Parts 1, 2, 3, and 4)
Time Frame: Approximately 2 years
Disease control rate (disease control rate [DCR]: CR + PR + stable disease [SD]) and duration of SD per RECIST version 1.1 as assessed by the Investigator
Approximately 2 years
Maximum Observed Plasma Concentration (Cmax) (Parts 1, 2, 3, and 4)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Cmax is the highest observed plasma concentration of the study drug following administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Observed Concentration (Tmax)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Observed Concentration (Tmax) after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
AUClast reflects total drug exposure from dosing until the last measurable concentration after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time of Last Quantifiable Concentration (Tlast)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Tlast is the time at which the final measurable drug concentration is observed after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
AUCinf represents total drug exposure extrapolated to infinite time after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Terminal Elimination Half-Life (t½)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
t½ is the time required for the plasma concentration of the drug to decrease by half during the terminal elimination phase after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Time Frame: Cycle 1 Day 15 (each cycle is 21 days)
Cmax,ss is the maximum observed plasma concentration after achieving steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Concentration at Steady State (Tmax,ss)
Time Frame: Cycle 1 Day 15 (each cycle is 21 days)
Tmax,ss is the time from dosing to Cmax at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Trough Plasma Concentration at Steady State (Ctrough)
Time Frame: Cycle 1 Day 15 (each cycle is 21 days)
Ctrough is the concentration obtained immediately prior to the next scheduled dose at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUCtau)
Time Frame: Cycle 1 Day 15 (each cycle is 21 days)
AUCtau represents drug exposure over one full dosing interval at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Apparent Clearance (CL/F)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
CL/F is the apparent clearance of the drug after extravascular dosing after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Apparent Volume of Distribution (Vz/F)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Vz/F is the apparent volume of distribution following extravascular dosing after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Accumulation Ratio (Rac)
Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Rac is calculated as the ratio of AUC or Cmax at steady state compared with first dose, reflecting drug accumulation after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IDEAYA Biosciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2026

Primary Completion (Estimated)

April 30, 2028

Study Completion (Estimated)

April 30, 2028

Study Registration Dates

First Submitted

November 13, 2025

First Submitted That Met QC Criteria

December 9, 2025

First Posted (Actual)

December 11, 2025

Study Record Updates

Last Update Posted (Actual)

April 3, 2026

Last Update Submitted That Met QC Criteria

April 2, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDE892-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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