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

Purpose

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.

Condition

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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
  • Drug: LBL-007
    Administered intravenously.
  • Drug: Tislelizumab
    Administered intravenously.
    Other names:
    • BGB-A317
  • Drug: Bevacizumab or Bevacizumab biosimilar
    Administered intravenously
  • Drug: Capecitabine
    Administered in accordance with relevant local guidelines and/or prescribing information
Experimental
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
  • Drug: LBL-007
    Administered intravenously.
  • Drug: Tislelizumab
    Administered intravenously.
    Other names:
    • BGB-A317
  • Drug: Bevacizumab or Bevacizumab biosimilar
    Administered intravenously
  • Drug: Capecitabine
    Administered in accordance with relevant local guidelines and/or prescribing information
Experimental
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
  • Drug: LBL-007
    Administered intravenously.
  • Drug: Tislelizumab
    Administered intravenously.
    Other names:
    • BGB-A317
  • Drug: Bevacizumab or Bevacizumab biosimilar
    Administered intravenously
  • Drug: 5-Fluorouracil
    Administered in accordance with relevant local guidelines and/or prescribing information
Experimental
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)
  • Drug: LBL-007
    Administered intravenously.
  • Drug: Tislelizumab
    Administered intravenously.
    Other names:
    • BGB-A317
  • Drug: Bevacizumab or Bevacizumab biosimilar
    Administered intravenously
  • Drug: Capecitabine
    Administered in accordance with relevant local guidelines and/or prescribing information
  • Drug: 5-Fluorouracil
    Administered in accordance with relevant local guidelines and/or prescribing information
Experimental
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)
  • Drug: LBL-007
    Administered intravenously.
  • Drug: Tislelizumab
    Administered intravenously.
    Other names:
    • BGB-A317
  • Drug: Bevacizumab or Bevacizumab biosimilar
    Administered intravenously
  • Drug: Capecitabine
    Administered in accordance with relevant local guidelines and/or prescribing information
  • Drug: 5-Fluorouracil
    Administered in accordance with relevant local guidelines and/or prescribing information
Experimental
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)
  • Drug: LBL-007
    Administered intravenously.
  • Drug: Bevacizumab or Bevacizumab biosimilar
    Administered intravenously
  • Drug: Capecitabine
    Administered in accordance with relevant local guidelines and/or prescribing information
  • Drug: 5-Fluorouracil
    Administered in accordance with relevant local guidelines and/or prescribing information
Active Comparator
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)
  • Drug: LBL-007
    Administered intravenously.
  • Drug: Tislelizumab
    Administered intravenously.
    Other names:
    • BGB-A317
  • Drug: Bevacizumab or Bevacizumab biosimilar
    Administered intravenously
  • Drug: Capecitabine
    Administered in accordance with relevant local guidelines and/or prescribing information
  • Drug: 5-Fluorouracil
    Administered in accordance with relevant local guidelines and/or prescribing information

More Details

Status
Active, not recruiting
Sponsor
BeiGene

Study Contact