ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer
Purpose
This is a Phase 1b open-label, multiple dose/schedule sequential study to determine the safety and efficacy of the oxidative phosphorylation (OxPhos) pathway inhibitor ME-344 in combination with bevacizumab in subjects with recurrent mCRC.
Condition
- Colorectal Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Age ≥18 years - Histological or cytological documentation of adenocarcinoma of the colon or rectum that is metastatic (all other histological types are excluded) - Subjects who progressed or demonstrated intolerability to prior standard approved therapies which include fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapies, cetuximab/panitumumab (if clinically indicated e.g., RAS wild-type tumors) PD-1 or BRAF inhibitors (if clinically indicated), and/or other checkpoint inhibitors in the metastatic setting. - Previous treatment with any investigational drug or anticancer treatment must be completed >28 days or 5 half-lives, whichever is longer, before the first dose of study treatment. - Adequate bone marrow, liver, and renal function
Exclusion Criteria
- Untreated brain metastases, spinal cord compression, or primary brain tumor - Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor - Evidence of uncontrolled or unstable cardiovascular disease, myocardial infarction (within 6 months), unstable angina pectoris, congestive heart failure, serious arrhythmias requiring drug therapy - History of CNS disease - Bevacizumab or aflibercept therapy ≤ 3 weeks prior to starting study treatment - Peripheral neuropathy Grade ≥ 2 - Uncontrolled hypertension or diabetes mellitus, active peptic ulcers, unhealed wounds, clinically significant disease or systemic infections - Known seropositive for, or active infection with hepatitis B or C virus - Symptomatic or uncontrolled infection with human T-cell leukemia virus - Venous thromboembolism (unless appropriately treated and stable on anticoagulant for at least 2 weeks).
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Intervention Model Description
- This is a Phase 1b open-label, multiple dose/schedule sequential study to determine the safety and efficacy of the oxidative phosphorylation (OxPhos) pathway inhibitor ME-344 in combination with bevacizumab in subjects with recurrent mCRC. Subjects in Cohort 1 will receive ME-344 (IV) on Days 1, 8 and 15 combined with bevacizumab (IV) on Days 1 and 15 of each 28-day cycle. Subjects in Cohort 2 will receive ME 344 (IV) on Days 1 and 15 combined with bevacizumab (IV) on Days 1 and 15 of each 28-day cycle.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental ME-344 and Bevacizumab |
ME-344 (IV) Cohort 1: Days 1, 8, and 15 of each 28-day cycle. Cohort 2: Days 1 and 15 of each 28-day cycle. Bevacizumab (IV) Cohorts 1 and 2: Days 1 and 15 of each 28-day cycle. |
|
More Details
- Status
- Terminated
- Sponsor
- MEI Pharma, Inc.
Study Contact
Detailed Description
This is a Phase 1b open-label, multiple dose/schedule sequential study to determine the safety and efficacy of the oxidative phosphorylation (OxPhos) pathway inhibitor ME-344 in combination with bevacizumab in subjects with recurrent mCRC. This study will enroll subjects with metastatic CRC, including but not limited to subjects with RAS wild-type or mutant tumors, MSI-H/pMMR, and BRAF V600E, who have progressed or demonstrated intolerability to standard approved therapies which include fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapies, cetuximab/panitumumab, PD-1 inhibitors, or BRAF inhibitors (if clinically indicated), and/or other checkpoint inhibitors. Approximately 40 subjects will be enrolled in the study, in 2 cohorts of 20 subjects each. Subjects will continue treatment with ME-344 and bevacizumab until radiological progressive disease, unacceptable AEs, withdrawal of consent, start of new anticancer therapy, or death.