Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer
Conditions
Keywords
Colorectal Cancer, Microsatellite Stable, Mismatch Repair Proficient, Maintenance Therapy
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.
Interventions
DRUGLBL-007
Administered intravenously.
DRUGTislelizumab
Administered intravenously.
DRUGBevacizumab or Bevacizumab biosimilar
Administered intravenously
DRUGCapecitabine
Administered in accordance with relevant local guidelines and/or prescribing information
DRUG5-Fluorouracil
Administered in accordance with relevant local guidelines and/or prescribing information
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, China, Puerto Rico, United States
Outcome results
None listed