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

BeiGene

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer

Treatments: Drug: Alcestobart; Drug: Bevacizumab or Bevacizumab biosimilar; Drug: Fluoropyrimidine (FP); Drug: Tislelizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05609370

BGB-A317-LBL-007-201

CTR20223077 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 113 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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113 participants in 8 patient groups

Phase 1b: Alcestobart Low Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine

Experimental group

Description:

Participants received alcestobart low dose, tislelizumab, bevacizumab and capecitabine until disease progression, unacceptable toxicity, or withdrawal of consent.

Treatment:

Drug: Fluoropyrimidine (FP)

Drug: Tislelizumab

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: Alcestobart

Phase 1b: Alcestobart Medium Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine

Experimental group

Description:

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).

Treatment:

Drug: Fluoropyrimidine (FP)

Drug: Tislelizumab

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: Alcestobart

Phase 1b: Alcestobart High Dose + Tislelizumab + Bevacizumab + Fluoropyrimidine

Experimental group

Description:

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).

Treatment:

Drug: Fluoropyrimidine (FP)

Drug: Tislelizumab

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: Alcestobart

Phase 2: Arm A:PD-L1-positive: Alcestobart High Dose +Tislelizumab + Bevacizumab +Fluoropyrimidine

Experimental group

Description:

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).

Treatment:

Drug: Fluoropyrimidine (FP)

Drug: Tislelizumab

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: Alcestobart

Phase 2: Arm B: PD-L1-positive: Alcestobart High Dose + Bevacizumab + Fluoropyrimidine

Experimental group

Description:

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).

Treatment:

Drug: Fluoropyrimidine (FP)

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: Alcestobart

Phase 2: Arm C: PD-L1-positive: Bevacizumab + Fluoropyrimidine

Active Comparator group

Description:

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).

Treatment:

Drug: Fluoropyrimidine (FP)

Drug: Bevacizumab or Bevacizumab biosimilar

Phase 2: Arm D: PD-L1-negative: Alcestobart High Dose+ Tislelizumab+ Bevacizumab+ Fluoropyrimidine

Experimental group

Description:

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).

Treatment:

Drug: Fluoropyrimidine (FP)

Drug: Tislelizumab

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: Alcestobart

Phase 2: Arm E: PD-L1-negative: Bevacizumab + Fluoropyrimidine

Active Comparator group

Description:

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).

Treatment:

Drug: Fluoropyrimidine (FP)

Drug: Bevacizumab or Bevacizumab biosimilar