A Phase 2 Randomized Study to Evaluate the Safety, Efficacy, and Optimal Dose of Telisotuzumab Adizutecan in Combination With Fluorouracil, Leucovorin, and Budigalimab as First-Line Treatment in Subjects With Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (AndroMETa-GEA-977)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 185
- 试验地点
- 82
- 主要终点
- Progression-Free Survival (PFS) as Assessed by Investigator
研究概览
简要总结
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity when telisotuzumab adizutecan (ABBV-400) is given in combination with Fluorouracil, Leucovorin, and a programmed cell death receptor 1 (PD1) inhibitor Budigalimab. The combination (AFLB) will be given to adult participants to treat locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEA).
Telisotuzumab Adizutecan (ABBV-400) and Budigalimab are investigational drugs being developed for the treatment of mGEA. Fluorouracil and Leucovorin are drugs approved for the treatment of mGEA. This study will be divided into two stages, with the first stage treating participants with increasing doses of ABBV-400 within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. Participants will then be randomized into groups called treatment arms where one group will receive Budigalimab and FOLFOX (Fluorouracil, Leucovorin, and Oxaliplatin) . A further two treatment groups will receive AFLB, but with two optimized doses of ABBV-400 to allow for the best dose to be studied in the future. Approximately 180 adult participants with mGEA will be enrolled in the study in 51 sites worldwide.
In the dose escalation stage, participants will be treated with increasing intravenous (IV) doses of telisotuzumab adizutecan (ABBV-400) within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage, participants will receive FOLFOX or receive AFLB, but with one of two optimized doses of ABBV-400. 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
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Have inoperable, advanced or metastatic histologically- or cytologically confirmed gastric, gastroesophageal junction, or esophageal adenocarcinoma.
- •Have measurable disease determined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or
- •Human epidermal growth factor receptor 2 (HER2) negative disease, defined as immunohistochemistry (IHC) (0, or 1+) or fluorescence in situ hybridization (FISH) negative.
- •Known programmed death ligand 1 (PD-L1) status at screening, or availability of tumor tissue for central PD-L1 testing prior to enrollment.
排除标准
- •Have prior systemic therapy in the locally advanced, unresectable, or metastatic setting.
- •History of clinically significant, intercurrent lung-specific illnesses including, but not limited to those listed in the protocol.
研究组 & 干预措施
Stage 1: Dose Escalation ABBV-400
Participants will receive escalating doses of telisotuzumab adizutecan (ABBV-400) in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Stage 2 Arm 2: Dose Optimization ABBV-400 Dose B
Participants will receive telisotuzumab adizutecan (ABBV-400) dose B in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Stage 2 Arm 1: Dose Optimization ABBV-400 Dose A
Participants will receive telisotuzumab adizutecan (ABBV-400) dose A in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Stage 2 Arm 3: Dose Optimization Standard of Care (SOC)
Participants will receive a fixed dose of leucovorin (folinic acid), fluorouracil, oxaliplatin (FOLFOX) and budigalimab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Stage 1: Dose Escalation ABBV-400
Participants will receive escalating doses of telisotuzumab adizutecan (ABBV-400) in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Stage 2 Arm 1: Dose Optimization ABBV-400 Dose A
Participants will receive telisotuzumab adizutecan (ABBV-400) dose A in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Budigalimab (Drug)
Stage 1: Dose Escalation ABBV-400
Participants will receive escalating doses of telisotuzumab adizutecan (ABBV-400) in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Budigalimab (Drug)
Stage 2 Arm 2: Dose Optimization ABBV-400 Dose B
Participants will receive telisotuzumab adizutecan (ABBV-400) dose B in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Stage 2 Arm 3: Dose Optimization Standard of Care (SOC)
Participants will receive a fixed dose of leucovorin (folinic acid), fluorouracil, oxaliplatin (FOLFOX) and budigalimab as part of the approximately 6 year study duration.
干预措施: Budigalimab (Drug)
Stage 2 Arm 1: Dose Optimization ABBV-400 Dose A
Participants will receive telisotuzumab adizutecan (ABBV-400) dose A in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Leucovorin (Drug)
Stage 1: Dose Escalation ABBV-400
Participants will receive escalating doses of telisotuzumab adizutecan (ABBV-400) in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Stage 2 Arm 2: Dose Optimization ABBV-400 Dose B
Participants will receive telisotuzumab adizutecan (ABBV-400) dose B in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Stage 2 Arm 3: Dose Optimization Standard of Care (SOC)
Participants will receive a fixed dose of leucovorin (folinic acid), fluorouracil, oxaliplatin (FOLFOX) and budigalimab as part of the approximately 6 year study duration.
干预措施: Fluorouracil (Drug)
Stage 2 Arm 3: Dose Optimization Standard of Care (SOC)
Participants will receive a fixed dose of leucovorin (folinic acid), fluorouracil, oxaliplatin (FOLFOX) and budigalimab as part of the approximately 6 year study duration.
干预措施: Oxaliplatin (Drug)
Stage 2 Arm 2: Dose Optimization ABBV-400 Dose B
Participants will receive telisotuzumab adizutecan (ABBV-400) dose B in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Budigalimab (Drug)
Stage 2 Arm 1: Dose Optimization ABBV-400 Dose A
Participants will receive telisotuzumab adizutecan (ABBV-400) dose A in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Assessed by Investigator
时间窗: Through Study Completion, Approximately 6 Years
PFS is defined as the time from the first dose of study drug to the first occurrence of radiographic progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as determined by investigator or death from any cause, whichever occurs earlier.
Percentage of Participants with Objective Response (OR) as Assessed by Investigator
时间窗: Through Study Completion, Approximately 6 Years
OR is defined as confirmed complete response (CR) or confirmed partial response (PR) as assessed by investigator per RECIST version 1.1.
次要结局
- Duration of Response (DOR) as Assessed by Investigator(Through Study Completion, Approximately 6 Years)
- Overall Survival (OS)(Through Study Completion, Approximately 6 Years)
- Overall Survival (OS)(Through Study Completion, Approximately 6 Years)
- Percentage of Participants Achieving Disease Control (DC) as Assessed by Investigator(Through Study Completion, Approximately 6 Years)
- Duration of Response (DOR) as Assessed by Investigator(Through Study Completion, Approximately 6 Years)