Clinical trial NCT05824559: ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer
Official title: A Phase 1b Study of the OxPhos Inhibitor ME-344 Combined With Bevacizumab in Previously Treated Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Colorectal Cancer
Lead sponsor: MEI Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2023-04-21
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Progression Free Survival (PFS) Rate at 16 Weeks
timeFrame: 16 weeks
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 6 months
measure: Treatment Emergent Adverse Events for ME-344 Administered in Combination With Bevacizumab
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Miami
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: New Brunswick
country: United States
facility: Rutgers University
state: New Jersey
city: New York
country: United States
facility: Mt Sinai New York
state: New York
city: Nashville
country: United States
facility: Vanderbilt -Ingram Cancer Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
References: