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

Amgen

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: AMG 436

Study type: Interventional

Funder types: Industry

Identifiers

NCT07403721

20250004

2025-524056-63-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 464 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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464 participants in 5 patient groups

Part 1A

Experimental group

Description:

AMG 436 monotherapy dose escalation.

Treatment:

Drug: AMG 436

Part 1B: Food Effect Substudy

Experimental group

Description:

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

Treatment:

Drug: AMG 436

Part 2

Experimental group

Description:

AMG 436 + combination dose escalation.

Treatment:

Drug: AMG 436

Part 3

Experimental group

Description:

AMG 436 monotherapy Dose expansion and optimization.

Treatment:

Drug: AMG 436

Part 4

Experimental group

Description:

AMG 436 + chemotherapy combination dose expansions.

Treatment:

Drug: AMG 436