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 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

Exclusion Criteria

  • Participants whose disease has become resectable at the investigator's discretion during or after induction treatment are not eligible - Induction treatment initiated less than 6 months from completion of any prior neoadjuvant or adjuvant chemotherapy or radiotherapy which 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 + tislelizumab + bevacizumab + capecitabine
  • Drug: LBL-007
    Low dose intravenously (IV) once every 3 weeks.
  • Drug: Tislelizumab
    Low dose IV once every 3 weeks
    Other names:
    • BGB-A-317
  • Drug: Bevacizumab biosimilar
    7.5 mg/kg IV every 3 weeks
  • Drug: Capecitabine
    850 milligrams per square meter (mg/m^2) twice daily orally for 2 weeks, followed by a one-week treatment break every 3 weeks
Experimental
Phase 1b: Cohort 1a: LBL-007 + tislelizumab + bevacizumab + capecitabine 		LBL-007 + tislelizumab + bevacizumab + capecitabine
  • Drug: LBL-007
    Medium dose IV once every 3 weeks
  • Drug: Tislelizumab
    Low dose IV once every 3 weeks
    Other names:
    • BGB-A-317
  • Drug: Bevacizumab biosimilar
    7.5 mg/kg IV every 3 weeks
  • Drug: Capecitabine
    850 milligrams per square meter (mg/m^2) twice daily orally for 2 weeks, followed by a one-week treatment break every 3 weeks
Experimental
Phase 1b: Cohort 2: LBL-007 + tislelizumab + bevacizumab + fluoropyrimidine 		LBL-007 + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 2 weeks or 5 mg/kg once every 3 weeks)+ fluoropyrimidine (5-FU or capecitabine)
  • Drug: LBL-007
    High dose IV once every 2 or 3 weeks
  • Drug: Tislelizumab
    Low dose IV once every 3 weeks
    Other names:
    • BGB-A-317
  • Drug: Tislelizumab
    High dose IV once every 4 weeks
    Other names:
    • BGB-A-317
  • Drug: Bevacizumab biosimilar
    7.5 mg/kg IV every 3 weeks
  • Drug: Bevacizumab biosimilar
    5 mg/kg IV once every 2 weeks
  • Drug: Capecitabine
    850 milligrams per square meter (mg/m^2) twice daily orally for 2 weeks, followed by a one-week treatment break every 3 weeks
  • Drug: 5-Fluorouracil
    1600 to 2400 mg/m^2 IV every 2 weeks
Experimental
Phase 2: Arm A and Arm D: LBL-007 + tislelizumab + bevacizumab + fluoropyrimidine 		LBL-007 + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 2 weeks or 5 mg/kg once every 3 weeks) + fluoropyrimidine (5-FU or capecitabine)
  • Drug: LBL-007
    High dose IV once every 2 or 3 weeks
  • Drug: Tislelizumab
    Low dose IV once every 3 weeks
    Other names:
    • BGB-A-317
  • Drug: Tislelizumab
    High dose IV once every 4 weeks
    Other names:
    • BGB-A-317
  • Drug: Bevacizumab biosimilar
    7.5 mg/kg IV every 3 weeks
  • Drug: Bevacizumab biosimilar
    5 mg/kg IV once every 2 weeks
  • Drug: Capecitabine
    850 milligrams per square meter (mg/m^2) twice daily orally for 2 weeks, followed by a one-week treatment break every 3 weeks
  • Drug: 5-Fluorouracil
    1600 to 2400 mg/m^2 IV every 2 weeks
Experimental
Phase 2: Arm B: LBL-007 + bevacizumab + fluoropyrimidine 		LBL-007 + bevacizumab (7.5 mg/kgonce every 2 weeks or 5 mg/kg once every 3 weeks) + fluoropyrimidine (5-FU or capecitabine)
  • Drug: LBL-007
    High dose IV once every 2 or 3 weeks
  • Drug: Bevacizumab biosimilar
    7.5 mg/kg IV every 3 weeks
  • Drug: Bevacizumab biosimilar
    5 mg/kg IV once every 2 weeks
  • Drug: Capecitabine
    850 milligrams per square meter (mg/m^2) twice daily orally for 2 weeks, followed by a one-week treatment break every 3 weeks
  • Drug: 5-Fluorouracil
    1600 to 2400 mg/m^2 IV every 2 weeks
Other
Phase 2: Arm C and Arm E: bevacizumab + fluoropyrimidine 		bevacizumab (7.5 mg/kg once every 2 weeks or 5 mg/kg once every 3 weeks) + fluoropyrimidine (5-FU or capecitabine)
  • Drug: Bevacizumab biosimilar
    7.5 mg/kg IV every 3 weeks
  • Drug: Bevacizumab biosimilar
    5 mg/kg IV once every 2 weeks
  • Drug: Capecitabine
    850 milligrams per square meter (mg/m^2) twice daily orally for 2 weeks, followed by a one-week treatment break every 3 weeks
  • Drug: 5-Fluorouracil
    1600 to 2400 mg/m^2 IV every 2 weeks
Experimental
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5- Flurouracil (5-FU) 		LBL-007 + Tislelizumab + Bevacizumab + 5- Flurouracil
  • Drug: LBL-007
    Medium dose IV once every 3 weeks
  • Drug: Tislelizumab
    High dose IV once every 4 weeks
    Other names:
    • BGB-A-317
  • Drug: Bevacizumab biosimilar
    5 mg/kg IV once every 2 weeks
  • Drug: 5-Fluorouracil
    1600 to 2400 mg/m^2 IV every 2 weeks

Recruiting Locations

Ut Health San Antonio Mays Cancer Center
San Antonio, Texas 78229

More Details

Status
Recruiting
Sponsor
BeiGene

Study Contact

BeiGene
1-877-828-5568
clinicaltrials@beigene.com