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

NCT07277413 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IDE892-001
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 10

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.

Conditions

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

Keywords

MTAP deletion; MTAP loss; MTAP-deficient tumors; homozygous MTAP loss; IDE892; IDE397; MAT2A inhibitor; PRMT5; advanced solid tumors; metastatic cancer; recurrent cancer; dose escalation; dose expansion; phase 1 clinical trial; ctDNA

Outcome Measures

Primary Outcomes (3)

• Incidence of Dose-limiting Toxicities (DLTs) of IDE892 (Parts 1 and 3)

  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)

  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)

• Objective response rate (ORR) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Parts 2 and 4)

  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

Secondary Outcomes (15)

• Overall response rate (ORR) and duration of response (DOR) per RECIST version 1.1 (Parts 1 and 3)

  Approximately 2 years

• Disease control rate (DCR) and duration of stable disease per RECIST version 1.1 (Parts 1, 2, 3, and 4)

  Approximately 2 years

• Maximum Observed Plasma Concentration (Cmax) (Parts 1, 2, 3, and 4)

  Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

• Time to Maximum Observed Concentration (Tmax)

  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)

  Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Study Arms (4)

Part 1: IDE892 Monotherapy Dose Escalation (MTAP-deleted advanced solid tumors)

EXPERIMENTAL

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

Part 2: IDE892 Monotherapy Dose Expansion (MTAP-Deleted NSCLC)

EXPERIMENTAL

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

Part 3: IDE892 + IDE397 Combination Dose Escalation (MTAP-Deleted Solid Tumors)

EXPERIMENTAL

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; Drug: IDE397

Part 4: IDE892 + IDE397 Combination Dose Expansion (MTAP-Deleted NSCLC)

EXPERIMENTAL

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; Drug: IDE397

Interventions

IDE892 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 1: IDE892 Monotherapy Dose Escalation (MTAP-deleted advanced solid tumors); Part 2: IDE892 Monotherapy Dose Expansion (MTAP-Deleted NSCLC); Part 3: IDE892 + IDE397 Combination Dose Escalation (MTAP-Deleted Solid Tumors); Part 4: IDE892 + IDE397 Combination Dose Expansion (MTAP-Deleted NSCLC)

IDE397 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 3: IDE892 + IDE397 Combination Dose Escalation (MTAP-Deleted Solid Tumors); Part 4: IDE892 + IDE397 Combination Dose Expansion (MTAP-Deleted NSCLC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• IDEAYA Biosciences: lead

Study Sites (10)

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, 32827, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Sidney Kimmel Comprehensive Cancer Center Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

START Dallas Fort Worth

Fort Worth, Texas, 76104, United States

RECRUITING

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology Houston

Houston, Texas, 77054, United States

RECRUITING

NEXT Oncology Dallas

Irving, Texas, 75039, United States

RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Mesothelioma; Mesothelioma, Malignant; Neoplasm Metastasis; Recurrence

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Adenoma; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Central Study Contacts

IDEAYA Clinical Trials

CONTACT

+1 855 433 2246; IDEAYAClinicalTrials@ideayabio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: December 11, 2025
• Study Start: February 28, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (10)