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
- Conditions
- Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer
- Interventions
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 113
- 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
- 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)
Baptist Md Anderson Cancer Center
🇺🇸Jacksonville, Florida, United States
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
Shanxi Provincial Cancer Hospital
🇨🇳Taiyuan, Shanxi, China
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
University of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Pontchartrain Cancer Center
🇺🇸Covington, Louisiana, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
St Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Cancer Care Specialists
🇺🇸Reno, Nevada, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Perlmutter Cancer Center At Winthrop Oncology Hematology Associatesnyu Winthrop Hospital
🇺🇸Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center At Nyu Langone Health
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Ut Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Ut Health San Antonio Mays Cancer Center
🇺🇸San Antonio, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Cancer Care Northwest
🇺🇸Spokane Valley, Washington, United States
Multicare Health System Institute For Research and Innovation
🇺🇸Tacoma, Washington, United States
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Orange Health Service (Central West Cancer Care Centre)
🇦🇺Orange, New South Wales, Australia
Riverina Cancer Care Centre
🇦🇺Wagga Wagga, New South Wales, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Pindara Private Hospital
🇦🇺Benowa, Queensland, Australia
Icon Cancer Centre South Brisbane
🇦🇺South Brisbane, Queensland, Australia
Flinders Centre For Innovation in Cancer (Fcic)
🇦🇺Bedford Park, South Australia, Australia
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, South Australia, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
St John of God, Murdoch
🇦🇺Murdoch, Western Australia, Australia
One Clinical Research
🇦🇺Nedlands, Western Australia, Australia
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Beijing Tsinghua Changgung Hospital
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Quanzhou First Affliated Hospital of Fujian Medical University
🇨🇳Quanzhou, Fujian, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Gansu Provincial Hospital
🇨🇳Lanzhou, Gansu, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
🇨🇳Guangzhou, Guangdong, China
Zhujiang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Shantou University Medical College
🇨🇳Shantou, Guangdong, China
Nanyang Central Hospital
🇨🇳Nanyang, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
The First Peoples Hospital of Changzhou
🇨🇳Changzhou, Jiangsu, China
Nantong First Peoples Hospital
🇨🇳Nantong, Jiangsu, China
Affiliated Hospital of Jiangnan University South Campus
🇨🇳Wuxi, Jiangsu, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
Jining No.1 Peoples Hospital West Branch
🇨🇳Jining, Shandong, China
Linyi Peoples Hospital
🇨🇳Linyi, Shandong, China
Qingdao Municipal Hospital
🇨🇳Qingdao, Shandong, China
Renji Hospital Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Shanghai 10Th Peoples Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai East Hospital Branch Hospital
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Tianjin Union Medical Center (Nankai University Affiliated Hospital)
🇨🇳Tianjin, Tianjin, China
Karamay Central Hospital of Xinjiang
🇨🇳Karamay, Xinjiang, China
The Xinjiang Uygur Autonomous Region Peoples Hospital
🇨🇳Urumqi, Xinjiang, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Pan American Oncology Trials, Llc
🇵🇷Rio Piedras, Puerto Rico