A Phase 1b Study of the OxPhos Inhibitor ME-344 Combined With Bevacizumab in Previously Treated Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 7
- 主要终点
- Progression Free Survival (PFS) Rate at 16 Weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: ME-344 (Drug)
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.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Rate at 16 Weeks
时间窗: 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.
次要结局
- Overall Response Rate (ORR)(6 months)
- 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)