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
Study Details
Study Description
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 |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 |
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
|
| Experimental: Phase 2: Protein Ligand -1 (PD-L1) Positive Arm A LBL-007 + tislelizumab + bevacizumab + capecitabine |
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
|
| Experimental: Phase 2: Protein Ligand -1 (PD-L1) Positive Arm B LBL-007 + bevacizumab + capecitabine |
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
|
| Experimental: Phase 2: Protein Ligand -1 (PD-L1) Positive Arm C bevacizumab + capecitabine |
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
|
| Experimental: Phase 2: Protein Ligand -1 (PD-L1) Negative Arm D LBL-007 + tislelizumab + bevacizumab + capecitabine |
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
|
| Experimental: Phase 2: Protein Ligand -1 (PD-L1) Negative Arm E bevacizumab + capecitabine |
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
|
Outcome Measures
Primary Outcome Measures
- Phase 1b: Number of participants with Adverse events (AE) and Serious AEs (SAE) [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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) [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 [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 [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) [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 [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 [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 [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 [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 [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 [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))]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pindara Private Hospital | Benowa | Queensland | Australia | 4217 |
| 2 | Icon Cancer Care- South Brisbane | South Brisbane | Queensland | Australia | 4101 |
| 3 | Monash Health | Clayton | Victoria | Australia | 3168 |
| 4 | The Alfred Hospital | Melbourne | Victoria | Australia | 3004 |
| 5 | St John of God, Murdoch | Murdoch | Western Australia | Australia | 6150 |
| 6 | Jining No.1 People'S Hospital | Jining | Shandong | China | 272000 |
| 7 | Karamay Central Hospital of Xinjiang | Karamay | Xinjiang | China | 834000 |
| 8 | Zhejiang University College of Medicine- Second Affiliated Hospital | Hangzhou | Zhejiang | China | 310017 |
Sponsors and Collaborators
- BeiGene
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-A317-LBL-007-201