A Study Investigating the Efficacy and Safety of 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: Capecitabine; Drug: Tislelizumab; Drug: LBL-007; Drug: 5-Fluorouracil; Drug: Bevacizumab or Bevacizumab biosimilar

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 LBL-007 plus tislelizumab when administered in combination with bevacizumab plus fluoropyrimidine, and LBL-007 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 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 7 patient groups

Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine

Experimental group

Description:

LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine

Treatment:

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: Capecitabine

Drug: Tislelizumab

Drug: LBL-007

Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine

Experimental group

Description:

LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine

Treatment:

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: Capecitabine

Drug: Tislelizumab

Drug: LBL-007

Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)

Experimental group

Description:

LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU

Treatment:

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: 5-Fluorouracil

Drug: Tislelizumab

Drug: LBL-007

Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine

Experimental group

Description:

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)

Treatment:

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: 5-Fluorouracil

Drug: Capecitabine

Drug: Tislelizumab

Drug: LBL-007

Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine

Experimental group

Description:

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)

Treatment:

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: 5-Fluorouracil

Drug: Capecitabine

Drug: Tislelizumab

Drug: LBL-007

Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine

Experimental group

Description:

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)

Treatment:

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: 5-Fluorouracil

Drug: Capecitabine

Drug: LBL-007

Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine

Active Comparator group

Description:

Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)

Treatment:

Drug: Bevacizumab or Bevacizumab biosimilar

Drug: 5-Fluorouracil

Drug: Capecitabine

Drug: Tislelizumab

Drug: LBL-007