Study of BGB-A333 Alone and in Combination With Tislelizumab in Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-PD-L1 Monoclonal Antibody BGB-A333 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: BGB-A333
* Drug: BGB-A317


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1A: BGB-A333 monotherapy dose escalation<br> | Drug: BGB-A333<br>* Anti-PD-L1 antibody<br>|
| Experimental: Phase 2A: BGB-A333 monotherapy dose expansion<br> | Drug: BGB-A333<br>* Anti-PD-L1 antibody<br>|
| Experimental: Phase 1B: BGB-A333 and BGB-A317 dose confirmation<br> | Drug: BGB-A333<br>* Anti-PD-L1 antibody<br>Drug: BGB-A317<br>* Anti-PD-1 antibodies<br>* Other names: Tislelizumab;|
| Experimental: Phase 2B: BGB-A333 and BGB-A317 dose expansion<br> | Drug: BGB-A333<br>* Anti-PD-L1 antibody<br>Drug: BGB-A317<br>* Anti-PD-1 antibodies<br>* Other names: Tislelizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | 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. | Up to 33.5 months | 
| Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings | 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. | Up to 33.5 months | 
| Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) | 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. | Up to 33.5 months | 
| Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results | 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. | Up to 33.5 months | 
| Phase 1 A: Recommended Phase 2 Dose (RP2D) for BGB-333 | 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. | Up to 28 months | 
| Phase 2B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 | 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 | Up to 33.5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 | ORR is defined as the percentage of participants who had confirmed CR or PR assessed by investigator using RECIST version 1.1. | Up to 33.5 months | 
| Phase 2B: Duration of Response (DOR) Determined by Investigators Based on RECIST Version 1.1 | 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. | Up to 33.5 months | 
| Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 | DCR is defined as the percentage of participants with best overall response of CR, PR and Stable Disease. | Up to 33.5 months | 
| Phase 2B: Progression-free Survival (PFS) Determined by Investigators Based on RECIST Version 1.1 | 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 | Up to 33.5 months | 
| Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 | PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B pharmacokinetic (PK) parameters were not estimated due to limited sampling. | Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 | 
| Phase 1: Time to Cmax (Tmax) of BGB-A333 | PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling. | Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 | 
| Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333 | PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling. | Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 | 
| Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 | 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. | Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 | 
| Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333 | PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling. | Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 | 
| Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies | Treatment-emergent anti drug antibodies (ADA) was the sum of both treatment-induced ADA and treatment-boosted ADA, synonymous with ADA Incidence. | Up to 33.5 months |