Phase 1 Safety and Tolerability Study of Human Monoclonal Antibody 5B1 (MVT-5873) With Expansion in Subjects With Pancreatic Cancer or Other CA19-9 Positive Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 264
- 试验地点
- 5
- 主要终点
- Group D - Determine the safety (treatment related adverse events as assessed by Common Toxicity Criteria for Adverse Events [CTCAE] V5.0) of MVT-5873 on a Q2 week schedule
研究概览
简要总结
Phase 1 Safety and Tolerability Study in Subjects with Pancreatic Cancer or Other CA19-9 Positive Malignancies.
详细描述
Open label, multicenter, non-randomized, dose escalation/expansion trial of MVT-5873 as a single agent and in combination with standard of care chemotherapy or modified FOLFIRINOX (mFOLFIRINOX) in subjects with pancreatic and other CA19-9 positive malignancies. The study was designed to define a Maximum Tolerated Dose (MTD) of MVT-5873 as monotherapy (Group A), in combination with a standard of care chemotherapy (Group B), for a Q2 week schedule (Group D), an MTD of MVT-5873 for a Q4 week schedule (Group C), and an MTD for a Q2 week schedule of MVT-5873 in combination with mFOLFIRINOX (Groups E and F). Each group utilized a conventional 3+3 study design to identify the MTD and recommended phase 2 dose (RP2D).
Following the definition of the MTD in each group, the RP2D of MVT-5873 as a single agent and in combination with mFOLFIRINOX was defined. Following completion of monotherapy dose escalation, an expansion cohort of 30 additional subjects was treated at the RP2D for Group D. Subjects were subdivided into two groups of 15 subjects; those without peripheral blood expression of C19-9 and those with peripheral blood expression of CA19-9. MVT-5873 pharmacokinetics (PK) and pharmacodynamics (PD) were determined for each group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group A
MVT-5873 monotherapy dose escalation, initial to MTD
干预措施: MVT-5873 (Drug)
Group B
MVT-5873 is administered in Group B every 1 week in combination with gemcitabine and nab-paclitaxel
干预措施: MVT-5873 (Drug)
Group B
MVT-5873 is administered in Group B every 1 week in combination with gemcitabine and nab-paclitaxel
干预措施: gemcitabine + nab-paclitaxel (Drug)
Group C
MVT-5873 is administered in Group C every 4 weeks by intravenous infusion following a lead in dose. Each cycle is 28 days. During dose escalation, doses of MVT-5873 will be increased to define the MTD. Up to 30 patients will be treated at the RP2D.
干预措施: MVT-5873 (Drug)
Group D
MVT-5873 is administered in Group D every 2 weeks by intravenous infusion following a lead in dose. During dose escalation, doses of MVT-5873 will be increased to defined the MTD. Up to 30 patients will be treated at the RP2D.
干预措施: MVT-5873 (Drug)
Group E - metastatic
MVT-5873 is administered in combination with mFOLFIRINOX every 2 weeks. Both MVT-5873 and mFOLFIRINOX will be administered by intravenous infusion. During dose escalation, doses of MVT-5873, will be increased to define the MTD in combination with mFOLFIRINOX. mFOLFIRINOX will be administered according to institutional standards in compliance with the package insert for each drug. Up to 30 patients will be treated at the RP2D.
干预措施: MVT-5873 (Drug)
Group E - metastatic
MVT-5873 is administered in combination with mFOLFIRINOX every 2 weeks. Both MVT-5873 and mFOLFIRINOX will be administered by intravenous infusion. During dose escalation, doses of MVT-5873, will be increased to define the MTD in combination with mFOLFIRINOX. mFOLFIRINOX will be administered according to institutional standards in compliance with the package insert for each drug. Up to 30 patients will be treated at the RP2D.
干预措施: modified FOLFIRINOX (mFOLFIRINOX) (Drug)
Group F - adjuvant
MVT-5873 is administered in combination with mFOLFIRINOX every 2 weeks. Both MVT-5873 and mFOLFIRINOX will be administered by intravenous infusion. During dose escalation, doses of MVT-5873, will be increased to define the MTD in combination with mFOLFIRINOX. mFOLFIRINOX will be administered according to institutional standards in compliance with the package insert for each drug. Up to 30 patients will be treated at the RP2D.
干预措施: MVT-5873 (Drug)
Group F - adjuvant
MVT-5873 is administered in combination with mFOLFIRINOX every 2 weeks. Both MVT-5873 and mFOLFIRINOX will be administered by intravenous infusion. During dose escalation, doses of MVT-5873, will be increased to define the MTD in combination with mFOLFIRINOX. mFOLFIRINOX will be administered according to institutional standards in compliance with the package insert for each drug. Up to 30 patients will be treated at the RP2D.
干预措施: modified FOLFIRINOX (mFOLFIRINOX) (Drug)
结局指标
主要结局
Group D - Determine the safety (treatment related adverse events as assessed by Common Toxicity Criteria for Adverse Events [CTCAE] V5.0) of MVT-5873 on a Q2 week schedule
时间窗: Through study completion. Estimated at one year
Group F - Determine the safety (treatment related adverse events as assessed by CTCAE V5.0) of MVT-5873 in combination with the modified FOLFIRINOX regimen (mFOLFIRINOX) in the PDAC adjuvant setting
时间窗: Through study completion. Estimated at one year
Group F - Determine the MTD and/or the RP2D of MVT-5873 administered in combination with the modified FOLFIRINOX regimen (mFOLFIRINOX) in the PDAC adjuvant setting
时间窗: Through study completion. Estimated at one year
Group D - Determine the MTD and/or RP2D of MVT-5873 on a Q2 week schedule
时间窗: Through study completion. Estimated at one year
Group E - Determine the safety (treatment related adverse events as assessed by CTCAE V5.0) of MVT-5873 in combination with the modified FOLFIRINOX regimen (mFOLFIRINOX) in the metastatic disease setting
时间窗: Through study completion. Estimated at one year
Group E - Determine the MTD and/or the RP2D of MVT-5873 in combination with the modified FOLFIRINOX regimen (mFOLFIRINOX) in the metastatic disease setting
时间窗: Through study completion. Estimated at one year
次要结局
- Group F - Evaluate disease free survival(Through study completion. Estimated at one year)
- Groups A, B, C, D, E - Evaluate time to response(Through study completion. Estimated at one year)
- All groups - Evaluate overall survival(Through study completion. Estimated at one year)
- Group D - Evaluate the hepatic safety profile (treatment related adverse events as assessed by CTCAE V5.0) of MVT-5873 in participants without elevated circulating CA19-9 expression(Through study completion. Estimated at one year)
- All groups - Evaluate pharmacokinetics (PK): Area Under the Curve (AUC) for MVT-5873(Through study completion. Estimated at one year)
- Groups A, B, C, D, E - Evaluate tumor response rate(Through study completion. Estimated at one year)
- All groups - Evaluate PK: Maximum concentration (Cmax) for MVT-5873(Through study completion. Estimated at one year)
- All groups - Evaluate PK: Plasma half-life (T1/2) for MVT-5873(Through study completion. Estimated at one year)
- Groups A, B, C, D, E - Evaluate progression free survival(Through study completion. Estimated at one year)
- Group F - Evaluate time to recurrence(Through study completion. Estimated at one year)
- Groups A, B, C, D, E - Evaluate duration of response(Through study completion. Estimated at one year)