A Phase 1b/2, Randomized, Open-Label Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine as Maintenance Therapy in Patients With Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 113
- 试验地点
- 140
- 主要终点
- Phase 1b: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
研究概览
简要总结
This is a Phase 1b/2 study to investigate the efficacy and safety of alcestobart (LBL-007) plus tislelizumab when administered in combination with bevacizumab plus fluoropyrimidine, and alcestobart in combination with bevacizumab plus fluoropyrimidine versus bevacizumab plus fluoropyrimidine to participants with colorectal cancer.
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
- •Participant must have measurable disease as defined per RECIST((Response Evaluation Criteria in Solid Tumors) version 1.1
- •Has a histologically confirmed colorectal adenocarcinoma with metastatic or unresectable disease (Stage IV as defined by American Joint Committee on Cancer [AJCC] 8th edition)
- •No prior systemic therapy for colorectal cancer (CRC) in the metastatic setting except for the induction treatment of first-line therapy. Note: Local regional treatment performed during induction systemic treatment is allowed
- •Participants who have completed the first-line induction treatment, with an overall response of stable disease or better. The duration of induction treatment should be completed within approximately 6 months. The first dose of study treatment needs to occur within 2 weeks (for 2-week regimen) or 3 weeks (for 3-week regimen) to 6 weeks after Day 1 of the last cycle of induction therapy
排除标准
- •Participants whose disease has become resectable at the investigator's discretion during or after induction treatment are not eligible
- •Progressive disease occurred less than 6 months from completion of any prior neoadjuvant therapy (ie, chemotherapy with or without radiotherapy) or adjuvant therapy (ie, chemotherapy with or without radiotherapy), whichever occurred later
- •Participants who have been treated with anti-epidermal growth factor receptor (EGFR) antibody in the induction treatment
- •Any prior therapy targeting T-cell stimulation or checkpoint pathways
- •Participants with B-raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutations
- •Have locally or centrally confirmed microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR) method or dMMR by immunohistochemistry (IHC) method
- •Note: Other protocol defined criteria may apply.
研究组 & 干预措施
Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
干预措施: LBL-007 (Drug)
Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
干预措施: Tislelizumab (Drug)
Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
干预措施: Capecitabine (Drug)
Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
干预措施: LBL-007 (Drug)
Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
干预措施: Tislelizumab (Drug)
Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
干预措施: Capecitabine (Drug)
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)
LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU
干预措施: LBL-007 (Drug)
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)
LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU
干预措施: Tislelizumab (Drug)
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)
LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)
LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU
干预措施: 5-Fluorouracil (Drug)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: LBL-007 (Drug)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Tislelizumab (Drug)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Capecitabine (Drug)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: 5-Fluorouracil (Drug)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: LBL-007 (Drug)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Tislelizumab (Drug)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Capecitabine (Drug)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: 5-Fluorouracil (Drug)
Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: LBL-007 (Drug)
Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Capecitabine (Drug)
Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine
LBL-007 (high dose) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: 5-Fluorouracil (Drug)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine
Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: LBL-007 (Drug)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine
Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Tislelizumab (Drug)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine
Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine
Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: Capecitabine (Drug)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine
Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
干预措施: 5-Fluorouracil (Drug)
Phase 1b: Alcestobart Low Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart low dose, tislelizumab, bevacizumab and capecitabine until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Alcestobart (Drug)
Phase 2: Arm B: PD-L1-positive: Alcestobart High Dose + Bevacizumab + Fluoropyrimidine
PD-L1-positive participants received alcestobart high dose, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Alcestobart (Drug)
Phase 2: Arm B: PD-L1-positive: Alcestobart High Dose + Bevacizumab + Fluoropyrimidine
PD-L1-positive participants received alcestobart high dose, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Fluoropyrimidine (FP) (Drug)
Phase 2: Arm D: PD-L1-negative: Alcestobart High Dose+ Tislelizumab+ Bevacizumab+ Fluoropyrimidine
PD-L1-negative participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Alcestobart (Drug)
Phase 1b: Alcestobart Low Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart low dose, tislelizumab, bevacizumab and capecitabine until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Fluoropyrimidine (FP) (Drug)
Phase 1b: Alcestobart Low Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart low dose, tislelizumab, bevacizumab and capecitabine until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Tislelizumab (Drug)
Phase 1b: Alcestobart Medium Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart medium dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Alcestobart (Drug)
Phase 1b: Alcestobart Medium Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart medium dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Fluoropyrimidine (FP) (Drug)
Phase 1b: Alcestobart High Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent.
The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Alcestobart (Drug)
Phase 1b: Alcestobart High Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent.
The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Tislelizumab (Drug)
Phase 1b: Alcestobart High Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent.
The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Fluoropyrimidine (FP) (Drug)
Phase 2: Arm A:PD-L1-positive: Alcestobart High Dose +Tislelizumab + Bevacizumab +Fluoropyrimidine
PD-L1 (programmed cell death protein ligand-1)-positive participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Alcestobart (Drug)
Phase 2: Arm A:PD-L1-positive: Alcestobart High Dose +Tislelizumab + Bevacizumab +Fluoropyrimidine
PD-L1 (programmed cell death protein ligand-1)-positive participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Fluoropyrimidine (FP) (Drug)
Phase 2: Arm B: PD-L1-positive: Alcestobart High Dose + Bevacizumab + Fluoropyrimidine
PD-L1-positive participants received alcestobart high dose, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 2: Arm C: PD-L1-positive: Bevacizumab + Fluoropyrimidine
PD-L1-positive participants received bevacizumab and fluoropyrimidine in combination with leucovorin or levoleucovorin (LV) until disease progression, unacceptable toxicity, or withdrawal of consent.
The bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Fluoropyrimidine (FP) (Drug)
Phase 2: Arm D: PD-L1-negative: Alcestobart High Dose+ Tislelizumab+ Bevacizumab+ Fluoropyrimidine
PD-L1-negative participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Fluoropyrimidine (FP) (Drug)
Phase 2: Arm E: PD-L1-negative: Bevacizumab + Fluoropyrimidine
PD-L1-negative participants received bevacizumab and fluoropyrimidine in combination with LV until disease progression, unacceptable toxicity, or withdrawal of consent.
The bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Fluoropyrimidine (FP) (Drug)
Phase 1b: Alcestobart Low Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart low dose, tislelizumab, bevacizumab and capecitabine until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 1b: Alcestobart Medium Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart medium dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Tislelizumab (Drug)
Phase 1b: Alcestobart Medium Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart medium dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 1b: Alcestobart High Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine
Participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent.
The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 2: Arm A:PD-L1-positive: Alcestobart High Dose +Tislelizumab + Bevacizumab +Fluoropyrimidine
PD-L1 (programmed cell death protein ligand-1)-positive participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Tislelizumab (Drug)
Phase 2: Arm A:PD-L1-positive: Alcestobart High Dose +Tislelizumab + Bevacizumab +Fluoropyrimidine
PD-L1 (programmed cell death protein ligand-1)-positive participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 2: Arm C: PD-L1-positive: Bevacizumab + Fluoropyrimidine
PD-L1-positive participants received bevacizumab and fluoropyrimidine in combination with leucovorin or levoleucovorin (LV) until disease progression, unacceptable toxicity, or withdrawal of consent.
The bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 2: Arm D: PD-L1-negative: Alcestobart High Dose+ Tislelizumab+ Bevacizumab+ Fluoropyrimidine
PD-L1-negative participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
Phase 2: Arm D: PD-L1-negative: Alcestobart High Dose+ Tislelizumab+ Bevacizumab+ Fluoropyrimidine
PD-L1-negative participants received alcestobart high dose, tislelizumab, bevacizumab and fluoropyrimidine until disease progression, unacceptable toxicity, or withdrawal of consent. The alcestobart, tislelizumab, and bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Tislelizumab (Drug)
Phase 2: Arm E: PD-L1-negative: Bevacizumab + Fluoropyrimidine
PD-L1-negative participants received bevacizumab and fluoropyrimidine in combination with LV until disease progression, unacceptable toxicity, or withdrawal of consent.
The bevacizumab dosing frequency was based on the selected fluoropyrimidine regimen (5-FU/LV 2-week regimen or capecitabine 3-week regimen).
干预措施: Bevacizumab or Bevacizumab biosimilar (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
时间窗: From first dose of study drug up to 30 days after last dose; maximum time on treatment was 16.2 months.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatments, whether considered related to study treatments or not. A serious AE (SAE) was any untoward medical occurrence that, at any dose- * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Positive Arms A and C
时间窗: From randomization until disease progression, death, study discontinuation, or data cutoff, whichever occurred first (maximum follow-up time: Arm A, 11.0 months, Arm C, 8.0 months)
PFS, as assessed by the investigator per RECIST v1.1 is defined as the time from the date of randomization to the date of first documentation of disease progression or death, whichever occured first.
Phase 1b: Number of participants with Adverse Events (AEs) and Serious AEs (SAEs)
时间窗: From the first dose of study drug(s) to 30 days after last dose, initiation of new anticancer therapy, death, withdrawal of consent, or loss to follow-up, whichever occurs first (up to approximately 28 months)
Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 \[NCI-CTCAE v5.0\]).
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Positive Arms A and C
时间窗: Approximately 28 months
PFS, as assessed by the investigator per RECIST v1.1 is defined as the time from the date of randomization to the date of first documentation of disease progression or death, whichever occurs first.
次要结局
- Phase 2: Objective Response Rate (ORR) as Assessed by The Investigator in PD-L1 Positive Arms A and C(From randomization until disease progression, death, study discontinuation, or data cutoff, whichever occurred first (maximum follow-up time: Arm A, 11.0 months, Arm C, 8.0 months))
- Phase 2: Duration of Response (DOR) as Assessed by The Investigator in PD-L1 Positive Arms A and C(From first documented response until disease progression or death (maximum follow-up time for DOR was 4.2 months))
- Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Negative Arms D and E(From randomization until disease progression, death, study discontinuation, or data cutoff, whichever occurred first (maximum follow-up time: Arm D, 10.6 months, Arm E, 10.5 months))
- Phase 2: Objective Response Rate (ORR) as Assessed by The Investigator in PD-L1 Negative Arms D and E(From randomization until disease progression, death, study discontinuation, or data cutoff, whichever occurred first (maximum follow-up time: Arm D, 10.6 months, Arm E, 10.5 months)))
- Phase 2: Duration of Response (DOR) as Assessed by The Investigator in PD-L1 Negative Arms D and E(From first documented response until disease progression or death (maximum follow-up time for DOR was 2.8 months))
- Phase 2: Number of Participants With Treatment-emergent AEs and SAEs(From first dose of study drug up to 30 days after last dose; maximum time on treatment in Phase 2 was 10.9 months)
- Phase 2: Objective Response rate (ORR) as Assessed by The Investigator in PD-L1 Positive Arms A and C and PD-L1 Negative Arms D and E(Approximately 28 months)
- Phase 2: Duration of response (DOR) as Assessed by The Investigator in PD-L1 Positive Arms A and C and PD-L1 Negative arms D and E(Approximately 28 months)
- Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Negative Arms D and E(Approximately 28 months)
- Phase 2: Number of participants with AEs and SAEs(From the first dose of study drug(s) to 30 days after the last dose, initiation of new anticancer therapy, death, withdrawal of consent, or loss to follow-up, whichever occurs first (up to approximately 28 months))