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

Phase 1

Active, not recruiting

• Conditions: Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer
• Interventions: Drug: LBL-007; Drug: Tislelizumab; Drug: Bevacizumab or Bevacizumab biosimilar; Drug: Capecitabine; Drug: 5-Fluorouracil

• Registration Number: NCT05609370
• Lead Sponsor: BeiGene

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-10-20
• Study First Submitted QC: 2022-11-01
• Study First Posted: 2022-11-08
• Study Start: 2023-01-29
• Primary Completion: 2025-05-23
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-09
• Last Update Posted: 2025-06-11
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 113

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine	Bevacizumab or Bevacizumab biosimilar	LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine	Capecitabine	LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine	LBL-007	LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine	Tislelizumab	LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine	Bevacizumab or Bevacizumab biosimilar	LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine	Capecitabine	LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)	LBL-007	LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)	Tislelizumab	LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)	Bevacizumab or Bevacizumab biosimilar	LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU
Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU)	5-Fluorouracil	LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	LBL-007	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)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	Tislelizumab	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)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	Bevacizumab or Bevacizumab biosimilar	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)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	Capecitabine	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)
Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	5-Fluorouracil	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)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	LBL-007	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)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	Tislelizumab	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)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	Bevacizumab or Bevacizumab biosimilar	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)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	Capecitabine	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)
Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine	5-Fluorouracil	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)
Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine	LBL-007	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)
Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine	Bevacizumab or Bevacizumab biosimilar	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)
Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine	Capecitabine	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)
Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine	5-Fluorouracil	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)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine	LBL-007	Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine	Tislelizumab	Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine	Bevacizumab or Bevacizumab biosimilar	Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine	Capecitabine	Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine	5-Fluorouracil	Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)
Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine	LBL-007	LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine
Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine	Tislelizumab	LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine

Primary Outcome Measures

Name	Time	Method
Phase 1b: Number of participants with Adverse Events (AEs) and Serious AEs (SAEs)	From the first dose of study drug(s) to 30 days after last dose, initiation of new anticancer therapy, death, withdrawal of consent, or loss to follow-up, whichever occurs first (up to approximately 28 months)	Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 \[NCI-CTCAE v5.0\]).
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Positive Arms A and C	Approximately 28 months	PFS, as assessed by the investigator per RECIST v1.1 is defined as the time from the date of randomization to the date of first documentation of disease progression or death, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Phase 2: Objective Response rate (ORR) as Assessed by The Investigator in PD-L1 Positive Arms A and C and PD-L1 Negative Arms D and E	Approximately 28 months	ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) from the time of randomization.
Phase 2: Duration of response (DOR) as Assessed by The Investigator in PD-L1 Positive Arms A and C and PD-L1 Negative arms D and E	Approximately 28 months	DOR is defined as the time from the first confirmed objective response after randomization until the first documentation of disease progression or death, whichever comes first.
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Negative Arms D and E	Approximately 28 months	PFS, as assessed by the investigator per RECIST v1.1 is defined as the time from the date of randomization to the date of first documentation of disease progression or death, whichever occurs first.
Phase 2: Number of participants with AEs and SAEs	From the first dose of study drug(s) to 30 days after the last dose, initiation of new anticancer therapy, death, withdrawal of consent, or loss to follow-up, whichever occurs first (up to approximately 28 months)	Number of participants with AEs and SAEs characterized by type, frequency, severity as graded by NCI-CTCAE v5.0.

Trial Locations

Locations (76)

Alaska Oncology and Hematology, Llc; 🇺🇸 Anchorage, Alaska, United States

Banner Md Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

Toi Clinical Research; 🇺🇸 Cerritos, California, United States

Usc Norris Comprehensive Cancer Center (Nccc); 🇺🇸 Los Angeles, California, United States

Valkyrie Clinical Trials; 🇺🇸 Los Angeles, California, United States

UCLA; 🇺🇸 Los Angeles, California, United States

Hoag Memorial Presbyterian; 🇺🇸 Newport, California, United States

Kaiser Permanente Northern California; 🇺🇸 Vallejo, California, United States

Baptist Md Anderson Cancer Center; 🇺🇸 Jacksonville, Florida, United States

Fort Wayne Medical Oncology and Hematology; 🇺🇸 Fort Wayne, Indiana, United States

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