Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high (MSI-H) or Mismatched Repair Deficiency (dMMR)Phase 1NCT07403721
AMG 436 as Monotherapy and Combination Therapy in Participants With MSI-H/dMMR Solid Tumors
A Phase 1 study testing AMG 436 in people with Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high (MSI-H) or Mismatched Repair Deficiency (dMMR), run by Amgen at 27 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high (MSI-H) or Mismatched Repair Deficiency (dMMR)
- What is being tested?
- AMG 436
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 464 participants
- Where
- 27 sitesin 10 countries
- Study dates
- 8 Apr 2026to 1 Feb 2032
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
27 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
27 sites in 10 countries
United States7 sites, 7 recruiting
- Recruiting
Community Health Network MD Anderson Cancer Center - North
Indianapolis, Indiana, 46250
- Recruiting
City of Hope Orange County Lennar Foundation Cancer Center
Irvine, California, 92618
- Recruiting
Next Oncology - Dallas
Irving, Texas, 75039
- Recruiting
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
- Recruiting
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
- Recruiting
New England Cancer Specialists
Westbrook, Maine, 04092
- Recruiting
Midwestern Regional Medical Center dba City of Hope Chicago
Zion, Illinois, 60099
Japan4 sites, 4 recruiting
- Recruiting
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
- Recruiting
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
- Recruiting
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Koto-ku, Tokyo, 135-8550
- Recruiting
Aichi Cancer Center
Nagoya, Aichi-ken, 464-8681
France3 sites, 3 recruiting
- Recruiting
Hopital Saint Antoine
Paris, 75012
- Recruiting
Hopital Lyon sud
Pierre-Bénite, 69495
- Recruiting
Gustave Roussy
Villejuif, 94805
Spain3 sites, 3 recruiting
- Recruiting
Hospital Universitari Vall d Hebron
Barcelona, Catalonia, 08035
- Recruiting
Hospital Clinic i Provincial de Barcelona
Barcelona, Catalonia, 08036
- Recruiting
Clinica Universidad de Navarra
Madrid, 28027
Australia2 sites, 2 recruiting
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
- Recruiting
Calvary Mater Newcastle Hospital
Waratah, New South Wales, 2298
Belgium2 sites, 2 recruiting
- Recruiting
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
Brussels, 1200
- Recruiting
Universitair Ziekenhuis Gent
Ghent, 9000
China2 sites, 2 recruiting
- Recruiting
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong, 510060
- Recruiting
Zhongshan Hospital Fudan University
Shanghai, Shanghai Municipality, 200032
Taiwan2 sites, 2 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, 10002
- Recruiting
Taipei Veterans General Hospital
Taipei, 11217
Canada1 site, 1 recruiting
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z5
South Korea1 site, 1 recruiting
- Recruiting
Asan Medical Center
Seoul, 05505
About this study
Official title: 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.
- Being tested
- AMG 436
- Keywords
- AMG 436, MSI-H, dMMR, Solid Tumors
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 436Drug
AMG 436 will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Part 1A | Experimental | AMG 436 monotherapy dose escalation. Receives: Drug: AMG 436 |
| Part 1B: Food Effect Substudy | Experimental | Participants will receive AMG 436 under fasted and fed conditions (United States only). Receives: Drug: AMG 436 |
| Part 2 | Experimental | AMG 436 + combination dose escalation. Receives: Drug: AMG 436 |
| Part 3 | Experimental | AMG 436 monotherapy Dose expansion and optimization. Receives: Drug: AMG 436 |
| Part 4 | Experimental | AMG 436 + chemotherapy combination dose expansions. Receives: Drug: AMG 436 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with a Dose Limiting Toxicity (DLT)
Measured: Up to 21 days
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: Up to 5 years
Secondary outcomes (14)
Maximum Serum Concentration (Cmax) of AMG 436
Measured: Up to 57 days
Minimum Serum Concentration (Cmin) of AMG 436
Measured: Up to 57 days
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 436
Measured: Up to 57 days
Time to Achieve Cmax (Tmax) of AMG 436
Measured: Up to 57 days
Part 1B: Cmax of AMG 436 in the Fed and/or Fasted State
Measured: Up to 24 days
Part 1B: Tmax of AMG 436 in the Fed and/or Fasted State
Measured: Up to 24 days
Part 1B: AUC Over the Dosing Interval of AMG 436 in the Fed and/or Fasted State
Measured: Up to 24 days
Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Measured: Up to 5 years
Duration of Response (DOR) per RECIST v1.1
Measured: Up to 5 years
Time to Response (TTR) per RECIST v1.1
Measured: Up to 5 years
Disease Control Rate (DCR) per RECIST v1.1
Measured: Up to 5 years
Progression-free Survival (PFS) per RECIST v1.1
Measured: Up to 5 years
Overall Survival (OS) per RECIST v1.1
Measured: Up to 5 years
Change From Baseline in Tumor Phosphorylated Checkpoint Kinase 2 (CHK2) Following AMG 436
Measured: Baseline up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study start8 Apr 2026
- Primary completion1 Jan 2030 (estimated)
- Study completion1 Feb 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high (MSI-H) or Mismatched Repair Deficiency (dMMR)Studies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 464 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07403721
- Sponsor's protocol ID
- 20250004
- Other IDs
- 2025-524056-63-00, 2025
- Status last verified
- Oct 2026
- First submitted
- 5 Feb 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07403721
- Acronym / sponsor ID
- 20250004
- Keywords
- AMG 436, MSI-H, dMMR, Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 464 participants (estimated)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 8 Apr 2026 (actual)
- Primary completion
- 1 Jan 2030 (estimated)
- Study completion
- 1 Feb 2032 (estimated)
- First posted
- 11 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1A | Experimental | Drug: AMG 436AMG 436 monotherapy dose escalation. |
| Part 1B: Food Effect Substudy | Experimental | Drug: AMG 436Participants will receive AMG 436 under fasted and fed conditions (United States only). |
| Part 2 | Experimental | Drug: AMG 436AMG 436 + combination dose escalation. |
| Part 3 | Experimental | Drug: AMG 436AMG 436 monotherapy Dose expansion and optimization. |
| Part 4 | Experimental | Drug: AMG 436AMG 436 + chemotherapy combination dose expansions. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 436AMG 436 will be administered. | Drug | Part 1A, Part 1B: Food Effect Substudy, Part 2, Part 3, Part 4 |
Primary outcome
Number of Participants with a Dose Limiting Toxicity (DLT)
Time frame: Up to 21 days
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to 5 years
14 secondary outcomes
Maximum Serum Concentration (Cmax) of AMG 436
Time frame: Up to 57 days
Minimum Serum Concentration (Cmin) of AMG 436
Time frame: Up to 57 days
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 436
Time frame: Up to 57 days
Time to Achieve Cmax (Tmax) of AMG 436
Time frame: Up to 57 days
Part 1B: Cmax of AMG 436 in the Fed and/or Fasted State
Time frame: Up to 24 days
Part 1B: Tmax of AMG 436 in the Fed and/or Fasted State
Time frame: 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
Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Up to 5 years
Duration of Response (DOR) per RECIST v1.1
Time frame: Up to 5 years
Time to Response (TTR) per RECIST v1.1
Time frame: Up to 5 years
Disease Control Rate (DCR) per RECIST v1.1
Time frame: Up to 5 years
Progression-free Survival (PFS) per RECIST v1.1
Time frame: Up to 5 years
Overall Survival (OS) per RECIST v1.1
Time frame: Up to 5 years
Change From Baseline in Tumor Phosphorylated Checkpoint Kinase 2 (CHK2) Following AMG 436
Time frame: Baseline up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
MD study director
Amgen
27 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 436 in people with Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high (MSI-H) or Mismatched Repair Deficiency (dMMR), run by Amgen at 27 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Japan, France, Spain, Australia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amgen Call Center (866-572-6436, medinfo@amgen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with a Dose Limiting Toxicity (DLT) (time frame: Up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.