A Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Capecitabine Versus Bevacizumab Plus Capecitabine in Participants With Unresectable or Metastatic Colorectal Cancer
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| ClinicalTrials.gov Identifier: NCT05609370 |
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Recruitment Status :
Recruiting
First Posted : November 8, 2022
Last Update Posted : January 31, 2023
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Sponsor:
BeiGene
Information provided by (Responsible Party):
BeiGene
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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 capecitabine to participants with colorectal cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer | Drug: LBL-007 Drug: Tislelizumab Drug: Bevacizumab Drug: Capecitabine | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 202 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1b/2, Randomized, Open-Label Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Capecitabine Versus Bevacizumab Plus Capecitabine as Maintenance Therapy in Patients With Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer |
| Actual Study Start Date : | January 29, 2023 |
| Estimated Primary Completion Date : | February 2025 |
| Estimated Study Completion Date : | August 2026 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Phase 1b: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine
A modified 3+3 scheme will be used for evaluation of LBL-007 in 2 dose levels
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Drug: LBL-007
Low dose or high dose of LBL-007 once every 3 weeks intravenously Drug: Tislelizumab 200 milligrams (mg) intravenously once every 3 weeks Drug: Bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously once every 3 weeks Drug: Capecitabine 1000 milligrams per square meter (mg/m^2) twice daily orally on days 1 to 14 of each 21-day treatment cycle |
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Experimental: Phase 2: Protein Ligand -1 (PD-L1) Positive Arm A
LBL-007 + tislelizumab + bevacizumab + capecitabine
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Drug: LBL-007
High dose of LBL-007 once every 3 weeks intravenously Drug: Tislelizumab 200 milligrams (mg) intravenously once every 3 weeks Drug: Bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously once every 3 weeks Drug: Capecitabine 1000 milligrams per square meter (mg/m^2) twice daily orally on days 1 to 14 of each 21-day treatment cycle |
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Experimental: Phase 2: Protein Ligand -1 (PD-L1) Positive Arm B
LBL-007 + bevacizumab + capecitabine
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Drug: LBL-007
High dose of LBL-007 once every 3 weeks intravenously Drug: Bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously once every 3 weeks Drug: Capecitabine 1000 milligrams per square meter (mg/m^2) twice daily orally on days 1 to 14 of each 21-day treatment cycle |
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Experimental: Phase 2: Protein Ligand -1 (PD-L1) Positive Arm C
bevacizumab + capecitabine
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Drug: Bevacizumab
7.5 milligrams per kilogram (mg/kg) intravenously once every 3 weeks Drug: Capecitabine 1000 milligrams per square meter (mg/m^2) twice daily orally on days 1 to 14 of each 21-day treatment cycle |
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Experimental: Phase 2: Protein Ligand -1 (PD-L1) Negative Arm D
LBL-007 + tislelizumab + bevacizumab + capecitabine
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Drug: LBL-007
High dose of LBL-007 once every 3 weeks intravenously Drug: Tislelizumab 200 milligrams (mg) intravenously once every 3 weeks Drug: Bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously once every 3 weeks Drug: Capecitabine 1000 milligrams per square meter (mg/m^2) twice daily orally on days 1 to 14 of each 21-day treatment cycle |
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Experimental: Phase 2: Protein Ligand -1 (PD-L1) Negative Arm E
bevacizumab + capecitabine
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Drug: Bevacizumab
7.5 milligrams per kilogram (mg/kg) intravenously once every 3 weeks Drug: Capecitabine 1000 milligrams per square meter (mg/m^2) twice daily orally on days 1 to 14 of each 21-day treatment cycle |
Primary Outcome Measures :
- Phase 1b: Number of participants with Adverse events (AE) and Serious AEs (SAE) [ Time Frame: First Cycle of treatment (21 days) ]AEs and SAE are 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 [ Time Frame: Approximately 27 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 :
- Phase 2: Overall Survival (OS) as Assessed by The Investigator in PD-L1 Positive Arms A and C and PD-L1 Negative Arms D and E [ Time Frame: Approximately 27 months ]OS is defined as the time from the date of randomization until the date of death from any cause.
- Phase 2: PFS 2 as Assessed by The Investigator in PD-L1 Positive Arms A and C and PD-L1 Negative Arms D and E [ Time Frame: Approximately 27 months ]PFS2 is defined as the time from the date of randomization to the date of documentation of disease progression in second-line treatment, or death, whichever occurs first
- 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 [ Time Frame: Approximately 27 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 [ Time Frame: Approximately 27 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 [ Time Frame: Approximately 27 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: Progression Free Survival (PFS) as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression [ Time Frame: Approximately 27 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: Overall Survival (OS) as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression [ Time Frame: Approximately 27 months ]OS is defined as the time from the date of randomization until the date of death from any cause.
- Phase 2: PFS 2 as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression [ Time Frame: Approximately 27 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: Objective Response rate (ORR) as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression [ Time Frame: Approximately 27 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: DOR as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression [ Time Frame: Approximately 27 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 : Number of participants with Adverse events (AE) and Serious AEs (SAE) [ Time Frame: Up to last dose + 30 days (Approximately 27 months) ]AEs and SAE are characterized by type, frequency, severity as graded by NCI-CTCAE v5.0
- Phase 1b: Maximum Concentration (Cmax) of LBL-007 [ Time Frame: Cycle 1 Day 1 (C1D1) Predose, End of Infusion (EOI) 6 hours (h), C1D2, C1D4, C1D8, and C1D15, C2 to C25 D1 Predose and EOI (each cycle 21 days) ]
- Phase 1b: Time to achieve Maximum Concentration (Tmax) of LBL-007 [ Time Frame: Cycle 1 Day 1 (C1D1) Predose, End of Infusion (EOI) 6 hours (h), C1D2, C1D4, C1D8, and C1D15, C2 to C25 D1 Predose and EOI (each cycle 21 days) ]
- Phase 1b: Area Under the Concentration Curve from Day 0 to Day 21(AUC 0-21) [ Time Frame: Cycle 1 Day 1 (C1D1) Predose, End of Infusion (EOI) 6 hours (h), C1D2, C1D4, C1D8, and C1D15, C2 to C25 D1 Predose and EOI (each cycle 21 days) ]
- Phase 1b: Mean Half Life (t1/2) of LBL-007 [ Time Frame: Cycle 1 Day 1 (C1D1) Predose, End of Infusion (EOI) 6 hours (h), C1D2, C1D4, C1D8, and C1D15, C2 to C25 D1 Predose and EOI (each cycle 21 days) ]
- Phase 1b: Clearance (CL) of LBL-007 [ Time Frame: Cycle 1 Day 1 (C1D1) Predose, End of Infusion (EOI) 6 hours (h), C1D2, C1D4, C1D8, and C1D15, C2 to C25 D1 Predose and EOI (each cycle 21 days) ]
- Phase 1b: Apparent Volume of Distribution (Vz) of LBL-007 [ Time Frame: Cycle 1 Day 1 (C1D1) Predose, End of Infusion (EOI) 6 hours (h), C1D2, C1D4, C1D8, and C1D15, C2 to C25 D1 Predose and EOI (each cycle 21 days) ]
- Phase 2: Cmax of LBL-007, Tislelizumab, and Bevacizumab [ Time Frame: Up to approximately 27 months (predose at cycle 1,2,5,9,17, safety follow-up (each cycle 21 days)) ]
- Phase 2: Cmin of LBL-007, Tislelizumab, and Bevacizumab [ Time Frame: Cycle 1 Day 1 (C1D1) Predose, End of Infusion (EOI) 6 hours (h), C1D2, C1D4, C1D8, and C1D15, C2 to C25 D1 Predose and EOI (each cycle 21 days) ]
- Number of Participants with anti-drug antibodies (ADAs) to Tislelizumab, and Bevacizumab in Arm A, Arm B and Arm D [ Time Frame: Up to approximately 27 months (predose at cycle 1,2,5,9,17, safety follow-up, and EOI at cycle 1 and 5 (each cycle 21 days)) ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
- 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 documented B-raf proto-oncogene, serine/threonine kinase (BRAF) mutations by local assessments
- Have locally or centrally confirmed microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR) method or deficient mismatch repair (dMMR) immunohistochemistry (IHC). Local result is recommended and acceptable for enrollment. Participants without local testing results are required to have a central laboratory assessment. Note: CRC patients with tumors without mismatch repair (MMR) deficiency or MSI-H status are categorized as pMMR or microsatellite stable (MSS)
Note: Other protocol defined criteria may apply.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05609370
Contacts
| Contact: BeiGene | 1-877-828-5568 | clinicaltrials@beigene.com |
Locations
| Australia, Queensland | |
| Pindara Private Hospital | Recruiting |
| Benowa, Queensland, Australia, 4217 | |
| Icon Cancer Care- South Brisbane | Recruiting |
| South Brisbane, Queensland, Australia, 4101 | |
| Australia, Victoria | |
| Monash Health | Recruiting |
| Clayton, Victoria, Australia, 3168 | |
| The Alfred Hospital | Recruiting |
| Melbourne, Victoria, Australia, 3004 | |
| Australia, Western Australia | |
| St John of God, Murdoch | Recruiting |
| Murdoch, Western Australia, Australia, 6150 | |
| China, Shandong | |
| Jining No.1 People'S Hospital | Recruiting |
| Jining, Shandong, China, 272000 | |
| China, Xinjiang | |
| Karamay Central Hospital of Xinjiang | Recruiting |
| Karamay, Xinjiang, China, 834000 | |
| China, Zhejiang | |
| Zhejiang University College of Medicine- Second Affiliated Hospital | Recruiting |
| Hangzhou, Zhejiang, China, 310017 | |
Sponsors and Collaborators
BeiGene
| Responsible Party: | BeiGene |
| ClinicalTrials.gov Identifier: | NCT05609370 |
| Other Study ID Numbers: |
BGB-A317-LBL-007-201 |
| First Posted: | November 8, 2022 Key Record Dates |
| Last Update Posted: | January 31, 2023 |
| Last Verified: | January 2023 |
| 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 |
Additional relevant MeSH terms:
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Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Bevacizumab |
Capecitabine Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action |