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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05609370




Registration number
NCT05609370
Ethics application status
Date submitted
20/10/2022
Date registered
8/11/2022
Date last updated
28/10/2024

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
CTR20223077
Secondary ID [2] 0 0
BGB-A317-LBL-007-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LBL-007
Treatment: Drugs - LBL-007
Treatment: Drugs - LBL-007
Treatment: Drugs - Tislelizumab
Treatment: Drugs - Tislelizumab
Treatment: Drugs - Bevacizumab biosimilar
Treatment: Drugs - Bevacizumab biosimilar
Treatment: Drugs - Capecitabine
Treatment: Drugs - 5-Fluorouracil

Experimental: Phase 1b: Cohort-1: LBL-007 + tislelizumab + bevacizumab + capecitabine - LBL-007 + tislelizumab + bevacizumab + capecitabine

Experimental: Phase 1b: Cohort 1a: LBL-007 + tislelizumab + bevacizumab + capecitabine - LBL-007 + tislelizumab + bevacizumab + capecitabine

Experimental: Phase 1b: Cohort 2: LBL-007 + tislelizumab + bevacizumab + fluoropyrimidine - LBL-007 + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 2 weeks or 5 mg/kg once every 3 weeks)+ fluoropyrimidine (5-FU or capecitabine)

Experimental: Phase 2: Arm A and Arm D: LBL-007 + tislelizumab + bevacizumab + fluoropyrimidine - LBL-007 + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 2 weeks or 5 mg/kg once every 3 weeks) + fluoropyrimidine (5-FU or capecitabine)

Experimental: Phase 2: Arm B: LBL-007 + bevacizumab + fluoropyrimidine - LBL-007 + bevacizumab (7.5 mg/kgonce every 2 weeks or 5 mg/kg once every 3 weeks) + fluoropyrimidine (5-FU or capecitabine)

Other: Phase 2: Arm C and Arm E: bevacizumab + fluoropyrimidine - bevacizumab (7.5 mg/kg once every 2 weeks or 5 mg/kg once every 3 weeks) + fluoropyrimidine (5-FU or capecitabine)

Experimental: Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5- Flurouracil (5-FU) - LBL-007 + Tislelizumab + Bevacizumab + 5- Flurouracil


Treatment: Drugs: LBL-007
Low dose intravenously (IV) once every 3 weeks.

Treatment: Drugs: LBL-007
Medium dose IV once every 3 weeks

Treatment: Drugs: LBL-007
High dose IV once every 2 or 3 weeks

Treatment: Drugs: Tislelizumab
Low dose IV once every 3 weeks

Treatment: Drugs: Tislelizumab
High dose IV once every 4 weeks

Treatment: Drugs: Bevacizumab biosimilar
7.5 mg/kg IV every 3 weeks

Treatment: Drugs: Bevacizumab biosimilar
5 mg/kg IV once every 2 weeks

Treatment: Drugs: Capecitabine
850 milligrams per square meter (mg/m\^2) twice daily orally for 2 weeks, followed by a one-week treatment break every 3 weeks

Treatment: Drugs: 5-Fluorouracil
1600 to 2400 mg/m\^2 IV every 2 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Number of participants with Adverse events (AE) and Serious AEs (SAE)
Timepoint [1] 0 0
First Cycle of treatment (21 days)
Primary outcome [2] 0 0
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Positive Arms A and C
Timepoint [2] 0 0
Approximately 44 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Approximately 44 months
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Approximately 44 months
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Approximately 44 months
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Approximately 44 months
Secondary outcome [5] 0 0
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in PD-L1 Negative Arms D and E
Timepoint [5] 0 0
Approximately 44 months
Secondary outcome [6] 0 0
Phase 2: Progression Free Survival (PFS) as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression
Timepoint [6] 0 0
Approximately 44 months
Secondary outcome [7] 0 0
Phase 2: Overall Survival (OS) as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression
Timepoint [7] 0 0
Approximately 44 months
Secondary outcome [8] 0 0
Phase 2: PFS 2 as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression
Timepoint [8] 0 0
Approximately 44 months
Secondary outcome [9] 0 0
Phase 2: Objective Response rate (ORR) as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression
Timepoint [9] 0 0
Approximately 44 months
Secondary outcome [10] 0 0
Phase 2: DOR as Assessed by The Investigator in Arms A + D and Arms C + E Regardless of PD-L1 Expression
Timepoint [10] 0 0
Approximately 44 months
Secondary outcome [11] 0 0
Phase 2 : Number of participants with Adverse events (AE) and Serious AEs (SAE)
Timepoint [11] 0 0
Up to last dose + 30 days (Approximately 44 months)
Secondary outcome [12] 0 0
Phase 1b: Maximum Concentration (Cmax) of LBL-007
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Phase 1b: Time to achieve Maximum Concentration (Tmax) of LBL-007
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Phase 1b: Area Under the Concentration Curve from Day 0 to Day 21(AUC 0-21)
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Phase 1b: Mean Half Life (t1/2) of LBL-007
Timepoint [15] 0 0
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)
Secondary outcome [16] 0 0
Phase 1b: Clearance (CL) of LBL-007
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Phase 1b: Apparent Volume of Distribution (Vz) of LBL-007
Timepoint [17] 0 0
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)
Secondary outcome [18] 0 0
Phase 2: Cmax of LBL-007, Tislelizumab, and Bevacizumab
Timepoint [18] 0 0
Up to approximately 27 months (predose at cycle 1,2,5,9,17, safety follow-up (each cycle 21 days))
Secondary outcome [19] 0 0
Phase 2: Cmin of LBL-007, Tislelizumab, and Bevacizumab
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
Number of Participants with anti-drug antibodies (ADAs) to Tislelizumab, and Bevacizumab in Arm A, Arm B and Arm D
Timepoint [20] 0 0
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
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 which 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/01/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2028
Actual
Sample size
Target
226
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Cancer and Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment hospital [3] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [4] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [5] 0 0
Monash Health - Clayton
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [7] 0 0
St John of God, Murdoch - Murdoch
Recruitment hospital [8] 0 0
One Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2650 - Wagga Wagga
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
4217 - Benowa
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
China
State/province [8] 0 0
Anhui
Country [9] 0 0
China
State/province [9] 0 0
Beijing
Country [10] 0 0
China
State/province [10] 0 0
Fujian
Country [11] 0 0
China
State/province [11] 0 0
Guangdong
Country [12] 0 0
China
State/province [12] 0 0
Henan
Country [13] 0 0
China
State/province [13] 0 0
Hubei
Country [14] 0 0
China
State/province [14] 0 0
Hunan
Country [15] 0 0
China
State/province [15] 0 0
Jiangsu
Country [16] 0 0
China
State/province [16] 0 0
Shandong
Country [17] 0 0
China
State/province [17] 0 0
Shanghai
Country [18] 0 0
China
State/province [18] 0 0
Shanxi
Country [19] 0 0
China
State/province [19] 0 0
Tianjin
Country [20] 0 0
China
State/province [20] 0 0
Xinjiang
Country [21] 0 0
China
State/province [21] 0 0
Zhejiang
Country [22] 0 0
Puerto Rico
State/province [22] 0 0
Rio Piedras

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
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 to participants with colorectal cancer.
Trial website
https://clinicaltrials.gov/study/NCT05609370
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BeiGene
Address 0 0
Country 0 0
Phone 0 0
1-877-828-5568
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05609370