ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer

Phase 1

Terminated

Brief Summary: 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.

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.

Recruitment & Eligibility

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).

Arm && Interventions

Group	Intervention	Description
ME-344 and Bevacizumab	ME-344	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.
ME-344 and Bevacizumab	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) Rate at 16 Weeks	16 weeks	Progression Free Survival is measured by using laboratory testing and scans. It is measured by the length of time from first dose of study drug until observation of disease progression.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	6 months	Overall Response Rate (ORR) is defined/measured by the proportion of patients achieving complete response \[CR\] or partial response \[PR\] per RECIST v.1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Treatment Emergent Adverse Events for ME-344 Administered in Combination With Bevacizumab	from first dose of study drug on Cycle 1 Day 1 through 30 days after the last dose of study drug or start of new anticancer treatment, up to 11 months	This will be measured by the number of participants with at least one treatment emergent Adverse Events (abnormal physical examination findings, abnormal vital signs, abnormal ECG QT interval and abnormal clinical laboratory results)

Locations (7): Rutgers University
🇺🇸
New Brunswick, New Jersey, United States
Mt Sinai New York
🇺🇸
New York, New York, United States
Vanderbilt -Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
University of Southern California
🇺🇸
Los Angeles, California, United States
Mount Sinai Miami
🇺🇸
Miami Beach, Florida, United States
Johns Hopkins
🇺🇸
Baltimore, Maryland, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States