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

A Phase 1b/2, Randomized, Open-Label Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine as Maintenance Therapy in Patients With Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: LBL-007; Drug: Bevacizumab or Bevacizumab biosimilar; Drug: Capecitabine; Drug: 5-Fluorouracil

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Cancer and Haematology Centre
    • Orange, New South Wales, Australia, 2800
      • Orange Health Service (Central West Cancer Care Centre)
    • Wagga Wagga, New South Wales, Australia, 2650
      • Riverina Cancer Care Centre
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Pindara Private Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Centre South Brisbane
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Centre For Innovation in Cancer (Fcic)
    • Elizabeth Vale, South Australia, Australia, 5112
      • Lyell McEwin Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • St John of God, Murdoch
    • Nedlands, Western Australia, Australia, 6009
      • One Clinical Research
• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing Municipality, China, 102218
      • Beijing Tsinghua Changgung Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
    • Quanzhou, Fujian, China, 362000
      • Quanzhou First Affliated Hospital of Fujian Medical University
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Gansu Provincial Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • ZhuJiang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
    • Shantou, Guangdong, China, 515041
      • The First Affiliated Hospital of Shantou University Medical College
  • Henan
    • Nanyang, Henan, China, 473000
      • Nanyang Central Hospital
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • The First Peoples Hospital of Changzhou
    • Nantong, Jiangsu, China, 215124
      • Nantong First Peoples Hospital
    • Wuxi, Jiangsu, China, 214122
      • Affiliated Hospital of Jiangnan University South Campus
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Jining, Shandong, China, 272000
      • Jining No.1 Peoples Hospital West Branch
    • Linyi, Shandong, China, 276000
      • Linyi Peoples Hospital
    • Qingdao, Shandong, China, 266000
      • Qingdao Municipal Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200123
      • Shanghai East Hospital Branch Hospital
    • Shanghai, Shanghai Municipality, China, 200000
      • Renji Hospital Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai Municipality, China, 200072
      • Shanghai 10Th Peoples Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Shanxi Provincial Cancer Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin Municipality, China, 300121
      • Tianjin Union Medical Center (Nankai University Affiliated Hospital)
  • Xinjiang
    • Karamay, Xinjiang, China, 834009
      • Karamay Central Hospital of Xinjiang
    • Ürümqi, Xinjiang, China, 830001
      • The Xinjiang Uygur Autonomous Region Peoples Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Oncology Trials, LLC
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology, LLC
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Cerritos, California, United States, 90703
      • TOI Clinical Research
    • Los Angeles, California, United States, 90095
      • UCLA
    • Los Angeles, California, United States, 90067
      • Valkyrie Clinical Trials
    • Los Angeles, California, United States, 90033
      • Usc Norris Comprehensive Cancer Center (Nccc)
    • Newport, California, United States, 92663
      • Hoag Memorial Presbyterian
    • Vallejo, California, United States, 94510
      • Kaiser Permanente Northern California
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Markey Cancer Center
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
    • Louisville, Kentucky, United States, 40217
      • Norton Cancer Institute
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Pontchartrain Cancer Center
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59102
      • St Vincent Frontier Cancer Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
    • Reno, Nevada, United States, 89511
      • Cancer Care Specialists
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Mineola, New York, United States, 11501
      • Perlmutter Cancer Center At Winthrop Oncology Hematology Associatesnyu Winthrop Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio Mays Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Spokane Valley, Washington, United States, 99216
      • Cancer Care Northwest
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Tislelizumab; Administered intravenously.; Other Names: BGB-A317; Drug: LBL-007; Administered intravenously.; Other Names: Alcestobart; 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: Tislelizumab; Administered intravenously.; Other Names: BGB-A317; Drug: LBL-007; Administered intravenously.; Other Names: Alcestobart; 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: Tislelizumab; Administered intravenously.; Other Names: BGB-A317; Drug: LBL-007; Administered intravenously.; Other Names: Alcestobart; 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: Tislelizumab; Administered intravenously.; Other Names: BGB-A317; Drug: LBL-007; Administered intravenously.; Other Names: Alcestobart; 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: Tislelizumab; Administered intravenously.; Other Names: BGB-A317; Drug: LBL-007; Administered intravenously.; Other Names: Alcestobart; 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.; Other Names: Alcestobart; 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: Tislelizumab; Administered intravenously.; Other Names: BGB-A317; Drug: LBL-007; Administered intravenously.; Other Names: Alcestobart; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Number of participants with Adverse Events (AEs) and Serious AEs (SAEs)	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]).	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)
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Positive Arms A and C	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.	Approximately 28 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) from the time of randomization.	Approximately 28 months
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	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.	Approximately 28 months
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Negative Arms D and E	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.	Approximately 28 months
Phase 2: Number of participants with AEs and SAEs	Number of participants with AEs and SAEs characterized by type, frequency, severity as graded by NCI-CTCAE v5.0.	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)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2023
• Primary Completion (Actual): May 23, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 8, 2022

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Microsatellite Stable; Maintenance Therapy; Mismatch Repair Proficient
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Capecitabine; Bevacizumab; Fluorouracil; tislelizumab
• Other Study ID Numbers: BGB-A317-LBL-007-201; CTR20223077 (Registry Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No