A Study Investigating the Efficacy and Safety of Alcestobart (LBL-007) Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine in Participants With Unresectable or Metastatic Colorectal Cancer

Conditions

• Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Alcestobart — DRUG
  Administered intravenously (IV) at one of the following doses * Low dose: 150 mg once every 3 weeks * Medium dose: 300 mg once every 3 weeks or 200 mg once every 2 weeks * High dose: 600 mg once every 3 weeks or 400 mg once every 2 weeks
• Tislelizumab — DRUG
  Administered intravenously at a dose of either 200 mg once every 3 weeks or 300 mg once every 4 weeks.
• Bevacizumab or Bevacizumab biosimilar — DRUG
  Administered intravenously at a dose of either 7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks.
• Fluoropyrimidine (FP) — DRUG
  Fluoropyrimidine treatment included one of the following: \- Capecitabine 850 mg/m\^2 administered orally twice daily for the first 2 weeks of each 3-week cycle, OR \- 5-fluorouracil (5-FU) 1600 to 2400 mg/m\^2 continuous infusion over 46 to 48 hours in combination with leucovorin or levoleucovorin (LV) IV administered per local guidelines and/or prescribing information once every 2 weeks.

Study Details

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.

Key Dates

First listed

Nov 8, 2022

Start date

Jan 29, 2023

Status verified

Jun 2026

Primary completion

May 23, 2025

Completion

Dec 31, 2026

Study Design

Enrollment

113 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: 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.
• Experimental: 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).
• Experimental: 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).
• Experimental: 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).
• Experimental: 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).
• Active Comparator: 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).
• Experimental: 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).
• Active Comparator: 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).

Primary Outcome Measure

Phase 1b: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: From first dose of study drug up to 30 days after last dose; maximum time on treatment was 16.2 months. ]

Locations (30)

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