A Phase 2, Open-Label, Randomized, Master Protocol Study to Evaluate Safety and Efficacy of Multiple Treatment Combinations With Telisotuzumab Adizutecan in Subjects With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 390
- 试验地点
- 98
- 主要终点
- Objective Response (OR) as Assessed by the Investigator confirmed complete response (CR) or partial response (PR) as assessed by the investigator per response evaluation criteria in solid tumors (RECIST), version 1.1.
研究概览
简要总结
CRC is the third most common type of cancer diagnosed worldwide with developed countries at highest risk. The purpose of this study is to assess adverse events and change in disease activity when telisotuzumab adizutecan is given in combination with oxaliplatin, fluorouracil (5FU), leucovorin (LV) (FOLFOX), and bevacizumab or panitumumab.
Telisotuzumab adizutecan is an investigational drug being developed for the treatment of mCRC. Fluorouracil and leucovorin are drugs approved for the treatment of mCRC. This study will be divided into two stages, with the first stage treating participants with increasing doses of telisotuzumab adizutecan with FOLFOX and bevacizumab or 5FU/LV and panitumumab until the dose reached is tolerable and expected to be efficacious. Participants will then be randomized into 3 groups called treatment arms where one group will receive one of two optimized doses of telisotuzumab adizutecan from the dose escalation phase with FOLFOX and bevacizumab or 5FU/LV and panitumumab, or a comparator of FOLFOX and bevacizumab or panitumumab. Approximately 390 adult participants with mCRC will be enrolled in the study in 100 sites worldwide.
In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of telisotuzumab adizutecan with FOLFOX and bevacizumab or 5FU/LV and panitumumab until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive FOLFOX or receive 5FU/LV, but with one of two optimized doses of telisotuzumab adizutecan, or a comparator of FOLFOX and bevacizumab/pantitumumab. The study will run for a duration of approximately 6 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Laboratory values meeting the criteria within the protocol.
- •Has measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1.
排除标准
- •Prior systemic regimen containing c-Met targeting agent(s) (e.g., antibody, antibody drug conjugate, bispecific) and/or any topoisomerase inhibitor(s) (e.g., irinotecan).
- •History of other malignancies within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death.
研究组 & 干预措施
Substudy 1: Dose Expansion Compatator
Participants will receive a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Substudy 1: Dose Expansion Compatator
Participants will receive a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Bevacizumab (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Bevacizumab (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Bevacizumab (Drug)
Substudy 2: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Substudy 1: Dose Expansion Compatator
Participants will receive a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Oxaliplatin (Drug)
Substudy 1: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Substudy 2: Dose Expansion Compatator
Participants will receive a fixed dose of FOLFOX and panitumumab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Substudy 2: Dose Expansion Compatator
Participants will receive a fixed dose of FOLFOX and panitumumab as part of the approximately 6 year study duration.
干预措施: Panitumumab (Drug)
Substudy 2: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) and panitumumab as part of the approximately 6 year study duration.
干预措施: Panitumumab (Drug)
Substudy 2: Dose Expansion Compatator
Participants will receive a fixed dose of FOLFOX and panitumumab as part of the approximately 6 year study duration.
干预措施: Oxaliplatin (Drug)
Substudy 1: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Substudy 2: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Substudy 1: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration.
干预措施: Oxaliplatin (Drug)
Substudy 1: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration.
干预措施: Bevacizumab (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Substudy 2: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
干预措施: Panitumumab (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Substudy 1: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Substudy 2: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Substudy 2: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) and panitumumab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Oxaliplatin (Drug)
Substudy 2: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Substudy 2: Dose Expansion Compatator
Participants will receive a fixed dose of FOLFOX and panitumumab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Substudy 2: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
干预措施: Panitumumab (Drug)
Substudy 2: Dose Expansion Telisotuzumab Adizutecan Low Dose
Participants will receive the low dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Substudy 2: Dose Expansion Telisotuzumab Adizutecan High Dose
Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Substudy 1: Dose Expansion Compatator
Participants will receive a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration.
干预措施: Oxaliplatin (Drug)
Substudy 2: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) and panitumumab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Substudy 2: Dose Escalation Telisotuzumab Adizutecan
Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) and panitumumab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
结局指标
主要结局
Objective Response (OR) as Assessed by the Investigator confirmed complete response (CR) or partial response (PR) as assessed by the investigator per response evaluation criteria in solid tumors (RECIST), version 1.1.
时间窗: Up to 24 Weeks
OR is defined as confirmed CR or PR as assessed by the investigator per RECIST, version 1.1.
Number of Participants with Adverse Events (AE)s
时间窗: Up to Approximately 6 Years
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
次要结局
- Disease Control (DC) as Assessed by the Investigator(Up to Approximately 6 Years)
- Progression-Free Survival (PFS) as Assessed by the Investigator(Up to 22 Months)
- Duration of Response (DOR) as Assessed by the investigator(Up to 14 Months)
- Overall Survival (OS)(Up to Approximately 6 Years)