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: Active, not recruiting
• 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 (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sylwia Sobolewska; Phone Number: 347-522-0549; Email: ssobolewska@criterium.com

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	This will be measured using the Kaplan Meir (KM) method, and calculated from day of first study drug until observation of disease progression.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	This will be measure by the proportion of patients achieving complete response [CR] or partial response [PR] per RECIST v.1.1).	6 months
Safety and tolerability of ME-344 administered in combination with bevacizumab	This will be measured by the number of participants with treatment emergent Adverse Events, with abnormal physical examination findings, abnormal vital signs, abnormal ECG QT interval and abnormal clinical laboratory results	1 year

Collaborators and Investigators

• Sponsor: MEI Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): June 30, 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): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; 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