Advanced Solid Tumors
Conditions
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.
Interventions
DRUGBGB-A333
Anti-PD-L1 antibody
DRUGBGB-A317
Anti-PD-1 antibodies
Sponsors
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. 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 2. Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 3. Has adequate organ function Key
Exclusion criteria
1. Active brain or leptomeningeal metastasis. 2. Active autoimmune diseases or history of autoimmune diseases that may relapse. 3. 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) 4. Concurrent participation in another therapeutic clinical trial. 5. Received prior therapies targeting PD-1 or PD-L1. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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 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: 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 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 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 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 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 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. |
Countries
Australia, New Zealand, Spain
Participant flow
Recruitment details
This study was conducted at 8 study centers in Australia, 1 study center in New Zealand, and 3 study centers in Spain. A total of 39 patients were enrolled in the study and all received ≥ 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1A: BGB-A333 450 mg BGB-A333 450 mg, intravenously, every 3 weeks | 3 |
| Phase 1A: BGB-A333 900mg BGB-A333 900mg, intravenously, every 3 weeks | 3 |
| Phase 1A: BGB-A333 1350 mg BGB-A333 1350 mg, intravenously, every 3 weeks | 6 |
| Phase 1A: BGB-A333 1800 mg BGB-A333 1800 mg, intravenously, every 3 weeks | 3 |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg BGB-A333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks | 12 |
| Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg BGB-A333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks | 12 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Commenced new anti-cancer therapy | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 2 | 1 | 4 | 2 |
| Overall Study | Deteriorating condition | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Disease progression | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 0 | 1 | 1 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Phase 1A: BGB-A333 450 mg | Phase 1A: BGB-A333 900mg | Phase 1A: BGB-A333 1350 mg | Phase 1A: BGB-A333 1800 mg | Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.0 years STANDARD_DEVIATION 7.21 | 60.3 years STANDARD_DEVIATION 11.24 | 58.8 years STANDARD_DEVIATION 14.52 | 58.0 years STANDARD_DEVIATION 16.52 | 65.3 years STANDARD_DEVIATION 10.85 | 67.5 years STANDARD_DEVIATION 8.52 | 63.31 years STANDARD_DEVIATION 11.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 6 Participants | 3 Participants | 12 Participants | 11 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Programmed death-ligand 1 (PD-L1) Status Missing | 1 participants | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 3 participants |
| Programmed death-ligand 1 (PD-L1) Status Negative | 2 participants | 1 participants | 3 participants | 2 participants | 7 participants | 6 participants | 21 participants |
| Programmed death-ligand 1 (PD-L1) Status Positive | 0 participants | 2 participants | 2 participants | 1 participants | 4 participants | 6 participants | 15 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 6 Participants | 2 Participants | 12 Participants | 10 Participants | 36 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 7 Participants | 1 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants | 11 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 3 | 2 / 6 | 1 / 3 | 4 / 12 | 2 / 12 |
| other Total, other adverse events | 1 / 3 | 2 / 3 | 6 / 6 | 3 / 3 | 12 / 12 | 12 / 12 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 3 / 6 | 1 / 3 | 5 / 12 | 3 / 12 |
Outcome results
Primary
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.
Time frame: Up to 33.5 months
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) | 0 participants |
| Phase 1A: BGB-A333 900 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) | 1 participants |
| Phase 1A: BGB-A333 1350 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) | 5 participants |
| Phase 1A: BGB-A333 1800 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) | 2 participants |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) | 1 participants |
| Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) | 9 participants |
Primary
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.
Time frame: Up to 33.5 months
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings | 0 participants |
| Phase 1A: BGB-A333 900 mg | Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings | 0 participants |
| Phase 1A: BGB-A333 1350 mg | Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings | 0 participants |
| Phase 1A: BGB-A333 1800 mg | Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings | 0 participants |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings | 0 participants |
| Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings | 0 participants |
Primary
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.
Time frame: Up to 33.5 months
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results | 3 participants |
| Phase 1A: BGB-A333 900 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results | 3 participants |
| Phase 1A: BGB-A333 1350 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results | 6 participants |
| Phase 1A: BGB-A333 1800 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results | 3 participants |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results | 12 participants |
| Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results | 12 participants |
Primary
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.
Time frame: Up to 33.5 months
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Serious TEAE | 0 Participants |
| Phase 1A: BGB-A333 450 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Any Treatment Emergent Adverse Event (TEAE) | 1 Participants |
| Phase 1A: BGB-A333 900 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Any Treatment Emergent Adverse Event (TEAE) | 2 Participants |
| Phase 1A: BGB-A333 900 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Serious TEAE | 1 Participants |
| Phase 1A: BGB-A333 1350 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Any Treatment Emergent Adverse Event (TEAE) | 6 Participants |
| Phase 1A: BGB-A333 1350 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Serious TEAE | 3 Participants |
| Phase 1A: BGB-A333 1800 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Serious TEAE | 1 Participants |
| Phase 1A: BGB-A333 1800 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Any Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Any Treatment Emergent Adverse Event (TEAE) | 12 Participants |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Serious TEAE | 5 Participants |
| Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Serious TEAE | 3 Participants |
| Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events | Any Treatment Emergent Adverse Event (TEAE) | 12 Participants |
Primary
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.
Time frame: Up to 28 months
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1 A: Recommended Phase 2 Dose (RP2D) for BGB-333 | 1350 mg |
Primary
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
Time frame: Up to 33.5 months
Population: Safety Analysis Set (also used for efficacy analysis) included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 2B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 | 41.7 Percentage of participants |
Secondary
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.
Time frame: Up to 33.5 months
Population: Safety Analysis Set included (also used for efficacy analysis) all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 | 0.0 Percentage of participants |
| Phase 1A: BGB-A333 900 mg | Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 | 33.3 Percentage of participants |
| Phase 1A: BGB-A333 1350 mg | Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 | 50.0 Percentage of participants |
| Phase 1A: BGB-A333 1800 mg | Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 | 33.3 Percentage of participants |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 | 16.7 Percentage of participants |
Secondary
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.
Time frame: Up to 33.5 months
Population: ADA analysis set included participants who received ≥ 1 dose of study drug(s), BGB-A333 in Phase 1A or BGB-A333 and tislelizumab in Phase 1B and Phase 2B and had ≥ 1 evaluable ADA result after treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies | 1 participants |
| Phase 1A: BGB-A333 900 mg | Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies | 1 participants |
| Phase 1A: BGB-A333 1350 mg | Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies | 1 participants |
| Phase 1A: BGB-A333 1800 mg | Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies | 0 participants |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies | 0 participants |
| Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies | 4 participants |
Secondary
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.
Time frame: Up to 33.5 months
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 | 33.3 Percentage of participants |
| Phase 1A: BGB-A333 900 mg | Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 | 33.3 Percentage of participants |
| Phase 1A: BGB-A333 1350 mg | Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 | 66.7 Percentage of participants |
| Phase 1A: BGB-A333 1800 mg | Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 | 66.7 Percentage of participants |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 | 58.3 Percentage of participants |
| Phase 2B (Urothelial Carcinoma Cohort): BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 | 75.0 Percentage of participants |
Secondary
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.
Time frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Population: The PK analysis population includes all participants with valid PK sampling after treatment with study drug(s)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333 | 1095 μg*day/mL | Standard Deviation 141 |
| Phase 1A: BGB-A333 900 mg | Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333 | 2913 μg*day/mL | Standard Deviation 320 |
| Phase 1A: BGB-A333 1350 mg | Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333 | 3823 μg*day/mL | Standard Deviation 566 |
| Phase 1A: BGB-A333 1800 mg | Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333 | 4141 μg*day/mL | Standard Deviation 648 |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333 | 3546 μg*day/mL | Standard Deviation 814 |
Secondary
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.
Time frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Population: The PK analysis population includes all participants with valid PK sampling after treatment with study drug(s)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 | 167 μg/mL | Standard Deviation 42.4 |
| Phase 1A: BGB-A333 900 mg | Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 | 351 μg/mL | Standard Deviation 151 |
| Phase 1A: BGB-A333 1350 mg | Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 | 466 μg/mL | Standard Deviation 91 |
| Phase 1A: BGB-A333 1800 mg | Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 | 594 μg/mL | Standard Deviation 150 |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 | 455 μg/mL | Standard Deviation 127 |
Secondary
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.
Time frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Population: The PK analysis population includes all participants with valid PK sampling after treatment with study drug(s)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1: Time to Cmax (Tmax) of BGB-A333 | 0.05 Day |
| Phase 1A: BGB-A333 900 mg | Phase 1: Time to Cmax (Tmax) of BGB-A333 | 0.06 Day |
| Phase 1A: BGB-A333 1350 mg | Phase 1: Time to Cmax (Tmax) of BGB-A333 | 0.05 Day |
| Phase 1A: BGB-A333 1800 mg | Phase 1: Time to Cmax (Tmax) of BGB-A333 | 0.06 Day |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1: Time to Cmax (Tmax) of BGB-A333 | 0.21 Day |
Secondary
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.
Time frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Population: The PK analysis population includes all participants with valid PK sampling after treatment with study drug(s)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 | 22.0 Day |
| Phase 1A: BGB-A333 900 mg | Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 | 21.0 Day |
| Phase 1A: BGB-A333 1350 mg | Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 | 21.0 Day |
| Phase 1A: BGB-A333 1800 mg | Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 | 21.0 Day |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 | 21.0 Day |
Secondary
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.
Time frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Population: The PK analysis population includes all participants with valid PK sampling after treatment with study drug(s)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333 | 21.3 μg/mL | Standard Deviation 5.69 |
| Phase 1A: BGB-A333 900 mg | Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333 | 47.0 μg/mL | Standard Deviation 26.7 |
| Phase 1A: BGB-A333 1350 mg | Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333 | 90.7 μg/mL | Standard Deviation 24.2 |
| Phase 1A: BGB-A333 1800 mg | Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333 | 81.4 μg/mL | Standard Deviation 23.9 |
| Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg | Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333 | 80.0 μg/mL | Standard Deviation 22 |
Secondary
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.
Time frame: Up to 33.5 months
Population: Safety Analysis Set (also used for efficacy analysis) included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 2B: Duration of Response (DOR) Determined by Investigators Based on RECIST Version 1.1 | 9.6 Months |
Secondary
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
Time frame: Up to 33.5 months
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1A: BGB-A333 450 mg | Phase 2B: Progression-free Survival (PFS) Determined by Investigators Based on RECIST Version 1.1 | 6.1 Months |