Metastatic or Locally Advanced Solid Tumors With Microsatellite Instability-high (MSI-H) or Mismatched Repair Deficiency (dMMR)
Conditions
Keywords
AMG 436, MSI-H, dMMR, Solid Tumors
Brief 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.
Interventions
DRUGAMG 436
AMG 436 will be administered.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with a Dose Limiting Toxicity (DLT) | Up to 21 days |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Serum Concentration (Cmax) of AMG 436 | Up to 57 days |
| Minimum Serum Concentration (Cmin) of AMG 436 | Up to 57 days |
| Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 436 | Up to 57 days |
| Time to Achieve Cmax (Tmax) of AMG 436 | Up to 57 days |
| Part 1B: Cmax of AMG 436 in the Fed and/or Fasted State | Up to 24 days |
| Part 1B: Tmax of AMG 436 in the Fed and/or Fasted State | Up to 24 days |
| Part 1B: AUC Over the Dosing Interval of AMG 436 in the Fed and/or Fasted State | Up to 24 days |
| Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to 5 years |
| Duration of Response (DOR) per RECIST v1.1 | Up to 5 years |
| Time to Response (TTR) per RECIST v1.1 | Up to 5 years |
| Disease Control Rate (DCR) per RECIST v1.1 | Up to 5 years |
| Progression-free Survival (PFS) per RECIST v1.1 | Up to 5 years |
| Overall Survival (OS) per RECIST v1.1 | Up to 5 years |
| Change From Baseline in Tumor Phosphorylated Checkpoint Kinase 2 (CHK2) Following AMG 436 | Baseline up to 5 years |
Countries
Australia, Belgium, Canada, China, France, Japan, South Korea, Spain, Taiwan, United States
Contacts
CONTACTAmgen Call Center
STUDY_DIRECTORMD
Amgen
Outcome results
None listed