ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer

A Phase 1b Study of the OxPhos Inhibitor ME-344 Combined With Bevacizumab in Previously Treated Metastatic Colorectal Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: ME-344; Drug: Bevacizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Miami
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers University
  • New York
    • New York, New York, United States, 10029
      • Mt Sinai New York
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt -Ingram Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: ME-344; ME-344 will be administered intravenously (IV); Drug: Bevacizumab; Bevacizumab will be administered intravenously (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Rate at 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.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	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.	6 months
Treatment Emergent Adverse Events for ME-344 Administered in Combination With Bevacizumab	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)	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

Collaborators and Investigators

• Sponsor: MEI Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Actual): July 9, 2024
• Study Completion (Actual): July 23, 2024

Study Registration Dates

• First Submitted: March 22, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: ME-344-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No