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

NCT07403721 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 202500042025-524056-63-00
• Study Type: interventional
• Target: 464
• Locations: 8 countries
• Sites: 16

Brief 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.

Conditions

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

Keywords

AMG 436; MSI-H; dMMR; Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Number of Participants with a Dose Limiting Toxicity (DLT)

  Up to 21 days

• Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Up to 5 years

Secondary Outcomes (14)

• Maximum Serum Concentration (Cmax) of AMG 436

  Up to 57 days

• Minimum Serum Concentration (Cmin) of AMG 436

  Up to 57 days

• Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 436

  Up to 57 days

• Time to Achieve Cmax (Tmax) of AMG 436

  Up to 57 days

• Part 1B: Cmax of AMG 436 in the Fed and/or Fasted State

  Up to 24 days

Study Arms (5)

Part 1A

EXPERIMENTAL

AMG 436 monotherapy dose escalation.

Drug: AMG 436

Part 1B: Food Effect Substudy

EXPERIMENTAL

Participants will receive AMG 436 under fasted and fed conditions (United States only).

Drug: AMG 436

Part 2

EXPERIMENTAL

AMG 436 + combination dose escalation.

Drug: AMG 436

Part 3

EXPERIMENTAL

AMG 436 monotherapy Dose expansion and optimization.

Drug: AMG 436

Part 4

EXPERIMENTAL

AMG 436 + chemotherapy combination dose expansions.

Drug: AMG 436

Interventions

AMG 436 DRUG

AMG 436 will be administered.

Part 1A; Part 1B: Food Effect Substudy; Part 2; Part 3; Part 4

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Amgen: lead

Study Sites (16)

City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

RECRUITING

Midwestern Regional Medical Center dba City of Hope Chicago

Zion, Illinois, 60099, United States

RECRUITING

New England Cancer Specialists

Westbrook, Maine, 04092, United States

RECRUITING

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

RECRUITING

Next Oncology - Dallas

Irving, Texas, 75039, United States

RECRUITING

Calvary Mater Newcastle Hospital

Waratah, New South Wales, 2298, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

RECRUITING

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Central Study Contacts

Amgen Call Center

CONTACT

866-572-6436; medinfo@amgen.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: February 5, 2026
• First Posted: February 11, 2026
• Study Start: April 8, 2026
• Primary Completion (Estimated): June 28, 2028
• Study Completion (Estimated): June 28, 2028
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this trial will be considered beginning 18 months after the trial has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this trial.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen trial/trials in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (5); JP (4); CA (1); AU (2); CN (1); TW (1); BE (1); FR (1)