AMG 436 alone and with other treatments for adults with MSI‑High or dMMR advanced solid tumors

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

This trial tests AMG 436 alone and combined with other cancer therapies in adults whose advanced solid tumors are MSI‑High (MSI‑H) or mismatch repair deficient (dMMR).

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 464 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Amgen (Industry-sponsored)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 8 sites (Irving, Texas and 7 other locations)
• Trial ID: NCT07403721 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 dose‑finding trial of AMG 436 given as monotherapy and in combination with other anti‑cancer agents in adults with metastatic or locally advanced MSI‑H/dMMR solid tumors. The study enrolls participants with measurable disease, ECOG performance status 0–1, and adequate organ function, and requires available tumor tissue or a fresh biopsy. The primary goals are to define the safety profile and to determine the maximum tolerated dose or recommended phase 2 dose for AMG 436 in each treatment setting. Safety monitoring and dose escalation procedures will guide decisions about dose levels and combination cohorts.

Who should consider this trial

Good fit: Adults (or legal age in their country) with histologically confirmed MSI‑H or dMMR metastatic or locally advanced solid tumors, measurable disease, ECOG 0–1, and adequate organ function who can provide tumor tissue or undergo biopsy are ideal candidates.

Not a fit: Patients with primary central nervous system tumors, significant cardiac impairment, poor performance status, recent major surgery, or recent antitumor therapy are unlikely to qualify and therefore may not benefit from this trial.

Why it matters

Potential benefit: If successful, AMG 436 could offer a new treatment option that controls tumor growth for some patients with MSI‑H/dMMR advanced cancers.

How similar studies have performed: Immune checkpoint inhibitors have produced durable responses in many MSI‑H/dMMR cancers, but AMG 436 is an investigational agent with limited published clinical data so far.

Eligibility criteria

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).

Where this trial is running

Irving, Texas and 7 other locations

• Next Oncology - Dallas — Irving, Texas, United States (Recruiting)
• Calvary Mater Newcastle Hospital — Waratah, New South Wales, Australia (Recruiting)
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (Recruiting)
• Zhongshan Hospital Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)
• Aichi Cancer Center — Nagoya, Aichi-ken, Japan (Recruiting)
• National Cancer Center Hospital East — Kashiwa-shi, Chiba, Japan (Recruiting)
• National Cancer Center Hospital — Chuo-ku, Tokyo, Japan (Recruiting)
• The Cancer Institute Hospital of Japanese Foundation for Cancer Research — Koto-ku, Tokyo, Japan (Recruiting)

Study contacts

• Study coordinator: Amgen Call Center

Conditions Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high or Mismatched Repair Deficiency; AMG 436; MSI-H; dMMR; Solid Tumors