Colorectal Cancer
Conditions
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.
Interventions
DRUGME-344
ME-344 will be administered intravenously (IV)
DRUGBevacizumab
Bevacizumab will be administered intravenously (IV)
Sponsors
MEI Pharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
Participant flow
Recruitment details
This study was open from August of 2023 to July 2024 at 7 centers in the United States. 23 subjects were enrolled. Due to business reasons this study was terminated in July of 2024, and Cohort 2 was never opened.
Participants by arm
| Arm | Count |
|---|---|
| ME-344 and Bevacizumab ME-344 10 mg/kg (IV) Cohort 1: given on Days 1, 8, and 15 of each 28-day cycle.
Bevacizumab 5 mg/kg IV Cohort 1: given on Days 1 and 15 of each 28-day cycle. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Progressive Disease | 16 |
| Overall Study | Study Terminated by Sponsor | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | ME-344 and Bevacizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 23 |
| other Total, other adverse events | 22 / 23 |
| serious Total, serious adverse events | 11 / 23 |
Outcome results
Primary
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.
Time frame: 16 weeks
Population: All patients had relapsed metastatic colorectal cancer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ME-344 and Bevacizumab | Progression Free Survival (PFS) Rate at 16 Weeks | 31.8 percentage |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ME-344 and Bevacizumab | Overall Response Rate (ORR) | Stable Disease | 9 Participants |
| ME-344 and Bevacizumab | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| ME-344 and Bevacizumab | Overall Response Rate (ORR) | Partial Response | 0 Participants |
| ME-344 and Bevacizumab | Overall Response Rate (ORR) | Progressive Disease | 10 Participants |
| ME-344 and Bevacizumab | Overall Response Rate (ORR) | Not Available | 4 Participants |
Secondary
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)
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ME-344 and Bevacizumab | Treatment Emergent Adverse Events for ME-344 Administered in Combination With Bevacizumab | 22 Participants |