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NCT07403721PHASE1Recruiting

AMG 436 as Monotherapy and Combination Therapy in Participants With MSI-H/dMMR Solid Tumors

Amgen

Start Date

4/8/2026

Completion Date

7/28/2028

Summary

The primary objectives of this trial are to evaluate the safety profile of AMG 436 and to determine the maximum tolerated dose (MTD) and/or the recommended dose for AMG 436 as monotherapy and in combination with other anti-cancer therapies in participants with MSI-H/dMMR solid tumors.

Eligibility Criteria

Age Range: 18 years to 99 years

Inclusion Criteria: * Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years). * Histologically confirmed MSI-H or dMMR metastatic or locally advanced solid tumor by local testing or central testing. * Tumor tissue (formalin-fixed, paraffin-embedded sample) archival block must be available. Participants without archived tumor tissue may enroll by undergoing tumor biopsy before dosing. * Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). * Eastern Cooperative Oncology Group performance (ECOG) 0-1. * Adequate organ function as defined in the protocol. Exclusion Criteria: * Participants with primary central nervous system (CNS) tumors. * Impaired cardiac function or clinically significant cardiac disease. * Major surgery within 28 days of trial day 1. * Antitumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 21 days of first dose of trial treatment, unless anti-tumor therapy is a therapy with 5 times the half-life being shorter than 21 days (in this case, enrollment may be allowed with washout from prior therapy of \< 21 days. * Radiation therapy within 28 days of the first dose of trial treatment (or local or focal radiotherapy with palliative intent within 14 days of the first dose). * Gastrointestinal tract disease causing the inability to take per os (PO) medication, malabsorption syndrome, requirement for intravenous (IV) alimentation, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).

Interventions

DRUG

AMG 436

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Conditions

Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high (MSI-H) or Mismatched Repair Deficiency (dMMR)

Locations

City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California 92618

United States

Midwestern Regional Medical Center dba City of Hope Chicago

Zion, Illinois 60099

United States

Community Health Network MD Anderson Cancer Center - North

Indianapolis, Indiana 46250

United States

New England Cancer Specialists

Westbrook, Maine 04092

United States

Tennessee Oncology PLLC

Nashville, Tennessee 37203

United States

Next Oncology - Dallas

Irving, Texas 75039

United States

Calvary Mater Newcastle Hospital

Waratah, New South Wales 2298

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, 1200

Belgium

Universitair Ziekenhuis Gent

Ghent, 9000

Belgium

Princess Margaret Cancer Centre

Toronto, Ontario M5G 1Z5

Canada

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong 510060

China

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality 200032

China

Hopital Saint Antoine

Paris, 75012

France

Gustave Roussy

Villejuif, 94805

France

Aichi Cancer Center

Nagoya, Aichi-ken 464-8681

Japan

National Cancer Center Hospital East

Kashiwa-shi, Chiba 277-8577

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo 104-0045

Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo 135-8550

Japan

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia 08036

Spain

Clinica Universidad de Navarra

Madrid, 28027

Spain

Taipei Veterans General Hospital

Taipei, 11217

Taiwan