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

August 26, 2026 updated by: Amgen

A Phase 1/1b Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AMG 436 as Monotherapy and in Combination With Other Therapies in Participants With Microsatellite Instability-high (MSI-H)/Mismatch Repair Deficient (dMMR) Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
464

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • New South Wales
      • Waratah, New South Wales, Australia, 2298
        • Recruiting
        • Calvary Mater Newcastle Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Peter MacCallum Cancer Centre
  • Belgium
      • Brussels, Belgium, 1200
        • Recruiting
        • Universite Catholique de Louvain Cliniques Universitaires Saint Luc
      • Ghent, Belgium, 9000
        • Recruiting
        • Universitair Ziekenhuis Gent
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1Z5
        • Recruiting
        • Princess Margaret Cancer Centre
  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer Center
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Recruiting
        • Zhongshan Hospital Fudan University
  • France
      • Paris, France, 75012
        • Recruiting
        • Hopital Saint Antoine
      • Villejuif, France, 94805
        • Recruiting
        • Gustave Roussy
  • Japan
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 464-8681
        • Recruiting
        • Aichi Cancer Center
    • Chiba
      • Kashiwa-shi, Chiba, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
      • Koto-ku, Tokyo, Japan, 135-8550
        • Recruiting
        • The Cancer Institute Hospital of Japanese Foundation For Cancer Research
  • South Korea
      • Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center
  • Spain
      • Madrid, Spain, 28027
        • Recruiting
        • Clinica Universidad de Navarra
    • Catalonia
      • Barcelona, Catalonia, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall D Hebron
      • Barcelona, Catalonia, Spain, 08036
        • Recruiting
        • Hospital Clinic i Provincial de Barcelona
  • Taiwan
      • Taipei, Taiwan, 11217
        • Recruiting
        • Taipei Veterans General Hospital
  • United States
    • California
      • Irvine, California, United States, 92618
        • Recruiting
        • City of Hope Orange County Lennar Foundation Cancer Center
      • Newport Beach, California, United States, 92663
        • Recruiting
        • Hoag Memorial Hospital Presbyterian
    • Illinois
      • Zion, Illinois, United States, 60099
        • Recruiting
        • Midwestern Regional Medical Center dba City of Hope Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46250
        • Recruiting
        • Community Health Network MD Anderson Cancer Center - North
    • Maine
      • Westbrook, Maine, United States, 04092
        • Recruiting
        • New England Cancer Specialists
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Tennessee Oncology PLLC
    • Texas
      • Irving, Texas, United States, 75039
        • Recruiting
        • NEXT Oncology - Dallas

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1A
AMG 436 monotherapy dose escalation.
Drug: AMG 436
AMG 436 will be administered.
Experimental: Part 1B: Food Effect Substudy
Participants will receive AMG 436 under fasted and fed conditions (United States only).
Drug: AMG 436
AMG 436 will be administered.
Experimental: Part 2
AMG 436 + combination dose escalation.
Drug: AMG 436
AMG 436 will be administered.
Experimental: Part 3
AMG 436 monotherapy Dose expansion and optimization.
Drug: AMG 436
AMG 436 will be administered.
Experimental: Part 4
AMG 436 + chemotherapy combination dose expansions.
Drug: AMG 436
AMG 436 will be administered.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of Participants with a Dose Limiting Toxicity (DLT)
Time Frame: Up to 21 days
Up to 21 days
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 5 years
Up to 5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Maximum Serum Concentration (Cmax) of AMG 436
Time Frame: Up to 57 days
Up to 57 days
Minimum Serum Concentration (Cmin) of AMG 436
Time Frame: Up to 57 days
Up to 57 days
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 436
Time Frame: Up to 57 days
Up to 57 days
Time to Achieve Cmax (Tmax) of AMG 436
Time Frame: Up to 57 days
Up to 57 days
Part 1B: Cmax of AMG 436 in the Fed and/or Fasted State
Time Frame: Up to 24 days
Up to 24 days
Part 1B: Tmax of AMG 436 in the Fed and/or Fasted State
Time Frame: Up to 24 days
Up to 24 days
Part 1B: AUC Over the Dosing Interval of AMG 436 in the Fed and/or Fasted State
Time Frame: Up to 24 days
Up to 24 days
Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: Up to 5 years
Up to 5 years
Duration of Response (DOR) per RECIST v1.1
Time Frame: Up to 5 years
Up to 5 years
Time to Response (TTR) per RECIST v1.1
Time Frame: Up to 5 years
Up to 5 years
Disease Control Rate (DCR) per RECIST v1.1
Time Frame: Up to 5 years
Up to 5 years
Progression-free Survival (PFS) per RECIST v1.1
Time Frame: Up to 5 years
Up to 5 years
Overall Survival (OS) per RECIST v1.1
Time Frame: Up to 5 years
Up to 5 years
Change From Baseline in Tumor Phosphorylated Checkpoint Kinase 2 (CHK2) Following AMG 436
Time Frame: Baseline up to 5 years
Baseline up to 5 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: MD, Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 8, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 28, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 28, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 5, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 11, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20250004
  • 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
  • 2025-524056-63-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

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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