Study of BGB-A333 Alone and in Combination With Tislelizumab in Advanced Solid Tumors
- Conditions
- Advanced Solid Tumors
- Interventions
- Drug: BGB-A333Drug: BGB-A317
- Registration Number
- NCT03379259
- Lead Sponsor
- BeiGene
- Brief Summary
BGB-A333 is a humanized IgG1-variant monoclonal antibody against programmed cell death 1-ligand 1 (PD-L1), the ligand of an immune check point- receptor, programmed cell death-1 (PD-1). BGB-A317 is a humanized, IgG4-variant monoclonal antibody against PD-1. This study tested the safety and anti-tumor effect of BGB-A333 alone and in combination with BGB-A317 in participants with advanced solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 39
- Histologically or cytologically confirmed advanced or metastatic disease (unresectable) that is resistant to standard therapy or for which treatment is not available, not tolerated or refused
- Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
- Has adequate organ function
Key
- Active brain or leptomeningeal metastasis.
- Active autoimmune diseases or history of autoimmune diseases that may relapse.
- With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for participants with hepatocellular carcinoma)
- Concurrent participation in another therapeutic clinical trial.
- Received prior therapies targeting PD-1 or PD-L1.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1B: BGB-A333 and BGB-A317 dose confirmation BGB-A333 - Phase 1A: BGB-A333 monotherapy dose escalation BGB-A333 - Phase 2A: BGB-A333 monotherapy dose expansion BGB-A333 - Phase 1B: BGB-A333 and BGB-A317 dose confirmation BGB-A317 - Phase 2B: BGB-A333 and BGB-A317 dose expansion BGB-A333 - Phase 2B: BGB-A333 and BGB-A317 dose expansion BGB-A317 -
- Primary Outcome Measures
Name Time Method Phase 2B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 Up to 33.5 months The ORR is defined as the percentage of participants who had confirmed Complete Response (CR) or Partial response (PR) assessed by investigator using RECIST version 1.1
Phase 1 A: Recommended Phase 2 Dose (RP2D) for BGB-333 Up to 28 months RP2D for BGB-A333 alone and in combination with tislelizumab was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 1800 mg.
Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) Up to 33.5 months Central ECG data was used and the abnormality was determined by the evaluator (Investigating physician). Multiple tests such as QT, HR, PR, RR were used by the evaluator to determine abnormality. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results Up to 33.5 months Lab abnormality was based on ANRIND: if the measurement value \> upper limit of normal (ULN), it was considered Abnormal. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events Up to 33.5 months Adverse events were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events NCI-CTCAE Version 4.03 Serious Adverse Events (SAEs) were monitored from the date of informed consent. All adverse events (AEs) and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings Up to 33.5 months Complete physical examination including an evaluation of 1) head, eyes, ears, nose, throat, 2) cardiovascular, 3) dermatological, 4) musculoskeletal, 5) respiratory, 6) gastrointestinal, and 7) neurological systems was required to be performed at Screening. At subsequent visits (or as clinically indicated), limited, symptom-directed physical examinations were performed. Clinically significant Ophthalmology abnormalities were collected from case report forms. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
- Secondary Outcome Measures
Name Time Method Phase 1: Time to Cmax (Tmax) of BGB-A333 Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333 Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
Phase 2B: Duration of Response (DOR) Determined by Investigators Based on RECIST Version 1.1 Up to 33.5 months DOR was defined as the time from the first determination of an objective response per RECIST version 1.1, until the first documentation of progression or death, whichever occurs first. DOR was not evaluable in Phase 1A and Phase 1B.
Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 Up to 33.5 months ORR is defined as the percentage of participants who had confirmed CR or PR assessed by investigator using RECIST version 1.1.
Phase 2B: Progression-free Survival (PFS) Determined by Investigators Based on RECIST Version 1.1 Up to 33.5 months PFS was defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of disease progression assessed by investigator using RECIST v1.1 or death, whichever occurs first
Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies Up to 33.5 months Treatment-emergent anti drug antibodies (ADA) was the sum of both treatment-induced ADA and treatment-boosted ADA, synonymous with "ADA Incidence."
Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 Up to 33.5 months DCR is defined as the percentage of participants with best overall response of CR, PR and Stable Disease.
Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333 Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B pharmacokinetic (PK) parameters were not estimated due to limited sampling.
Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling. Actual observed time values for PK sampling, have an allowable time deviation (+/- 3 days) from the planned nominal time as pre-specified in the Visit Window section of the study protocol.
Trial Locations
- Locations (8)
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Nucleus Network
🇦🇺Melbourne, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Auckland City Hospital
🇳🇿Auckland, New Zealand
Institut Catala Doncologia
🇪🇸Barcelona, Spain
Start Madrid Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Monash Health
🇦🇺Clayton, Victoria, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia