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

NCT ID: NCT07277413

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-28
• Study Completion Date: 2028-04-30

Brief Summary

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.

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.

Conditions

NSCLC Adenocarcinoma; Gastroesophageal Cancer (GC); Gastric Adenocarcinoma; Adenocarcinoma of Esophagus; Squamous Cell Car. - Esophagus; Urothelial Carcinoma (UC); Bladder Cancer; Mesothelioma; Pleural Mesothelioma; Peritoneal Mesothelioma; Non-Small Cell Lung Cancer NSCLC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

IDE892

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

IDE892

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

IDE892

Intervention Type: DRUG

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.

IDE397

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

IDE892

Intervention Type: DRUG

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.

IDE397

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IDEAYA Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NEXT Oncology Houston

Houston, Texas, United States

Site Status: RECRUITING

NEXT Oncology Dallas

Irving, Texas, United States

Site Status: RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

IDEAYA Clinical Trials

Role: CONTACT

IDEAYAClinicalTrials@ideayabio.com

+1 855 433 2246

Facility Contacts

Emma Morales

Role: primary

emorales@nextoncology.com

832-384-7912

Mofopefoluwa Akinwale

Role: primary

fakinwale@nextoncology.com

972-893-8800

Maybelle De La Rosa

Role: primary

mdelarosa@nextoncology.com

703-783-4518

Other Identifiers

IDE892-001

Identifier Type: -

Identifier Source: org_study_id