AMG 436 as Monotherapy and Combination Therapy in Participants With MSI-H/dMMR Solid Tumors
Purpose
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.
Condition
- Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high (MSI-H) or Mismatched Repair Deficiency (dMMR)
Eligibility
- Eligible Ages
- Between 18 Years and 99 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1A |
AMG 436 monotherapy dose escalation. |
|
|
Experimental Part 1B: Food Effect Substudy |
Participants will receive AMG 436 under fasted and fed conditions (United States only). |
|
|
Experimental Part 2 |
AMG 436 + combination dose escalation. |
|
|
Experimental Part 3 |
AMG 436 monotherapy Dose expansion and optimization. |
|
|
Experimental Part 4 |
AMG 436 + chemotherapy combination dose expansions. |
|
Recruiting Locations
City of Hope Orange County Lennar Foundation Cancer Center
Irvine, California 92618
Irvine, California 92618
Midwestern Regional Medical Center dba City of Hope Chicago
Zion, Illinois 60099
Zion, Illinois 60099
New England Cancer Specialists
Westbrook, Maine 04092
Westbrook, Maine 04092
Tennessee Oncology PLLC
Nashville, Tennessee 37203
Nashville, Tennessee 37203
Next Oncology - Dallas
Irving, Texas 75039
Irving, Texas 75039
More Details
- Status
- Recruiting
- Sponsor
- Amgen