Advanced Cancer
Conditions
Brief summary
This study evaluated the safety, tolerability, pharmacokinetic profile and treatment effect of a new drug known as BGB-A317 in participants with advanced tumors.
Interventions
BIOLOGICALBGB-A317
In the dose escalation part, the dose levels were escalated following a modified 3+3 dose escalation scheme. In the scheduled exploration part, participants were assigned to doses and dose schedules. In the fixed dose exploration part, participants were assigned to dose group(s) not to exceed the maximum tolerated dose. In the dose expansion part, participants were assigned to different groups based on their tumor type.
Sponsors
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants must have had a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy was available. 1. For Phase 1A: no specific restriction 2. For Phase 1B: histology specified below: i. non-small cell lung cancer (participants with documented epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement should have been excluded) ii. ovarian cancer iii. gastric cancer iv. hepatocellular carcinoma (HCC, Barcelona-Clinic Liver Cancer stage C, stage B not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach, and Child-Pugh A) v. head and neck squamous cell carcinoma vi. esophageal carcinoma vii. triple negative breast cancer viii. cholangiocarcinoma ix. renal cell cancer, bladder cancer, melanoma, Merkel-cell carcinoma, sarcoma, gastrointestinal stromal tumor, or cutaneous squamous cell carcinoma. Or any other solid tumors with known microsatellite instability-high or mismatch repair deficient status, such as colorectal cancer or pancreatic cancer 2. Participants with previously treated brain metastasis (es) that were asymptomatic or radiographically/clinically stable and not requiring steroids medications for 4 weeks prior to enrollment were permitted. 3. Participants must have had archival tumor tissues or agreed to a tumor biopsy for analysis of predictive biomarkers such as programmed death-ligand 1 (PD-L1). (Fresh tumor biopsies were strongly recommended at baseline for biomarker analysis in participants with readily accessible tumor lesions and who consented to the biopsies). 4. Participants must have had measurable disease as defined per Response Evaluation Criteria in Solid Tumor Version 1.1. 5. Eastern Cooperative Oncology Group performance status of ≤ 1. 6. Participants must have had adequate organ function as indicated by the following laboratory values: * Absolute neutrophil count ≥ 1,500 /microliter * Platelets ≥ 100,000 / milliliter (mL) * Hemoglobin ≥ 9 grams/deciliter or ≥ 5.6 millimoles/liter * Serum creatinine ≤ 1.5 X upper limit of normal (ULN) * Serum total bilirubin ≤ 1.5 X ULN * Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 X ULN or ≤ 5 X ULN for participants with liver metastases * International normalized ratio or prothrombin time ≤ 1.5 X ULN * Activated partial thromboplastin time ≤ 1.5 X ULN Key
Exclusion criteria
1. History of severe hypersensitivity reactions to other Monoclonal antibodies. 2. Prior malignancy active within the previous 2 years except for tumor for which a participant was enrolled in the study, and locally curable cancers that had been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast. 3. Prior therapies targeting PD-1 or PD-L1. 4. Participants who failed to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers. 5. Participants with active autoimmune diseases or history of autoimmune diseases should have been excluded. 6. Participants should have been excluded if they had a condition requiring systemic treatment with either corticosteroids (\> 10 milligrams daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. 7. Had history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies. 8. Known history of human immunodeficiency virus. 9. Active infection requiring therapy, positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid except in participant with HCC, who met the following criteria: * Hepatitis B virus (HBV) viral load \< 200 international units/mL (approximately 1000 combined positive score/mL) * Participants with active HBV infection needed to be on anti-HBV suppression ≥ 3 months, throughout treatment and for 6 months after * Participants hepatitis C virus (HCV)-positive after successful treatment (defined as sustained virologic response \[SVR\] 12 or SVR 24) were allowed as long as 4 weeks had passed between completion of HCV therapy and start of study drug 10. Use of any vaccines against infectious diseases (for example, influenza, varicella) within 4 weeks (28 days) of initiation of study therapy and 60 days after the last administration of the study medication. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1A: Number of Participants Experiencing Adverse Events (AEs) | Day -28 through 5 years and 2 months | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product. All AEs were monitored per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version \[v\] 4.03 2010). |
| Phase 1A: Number Of Participants With Abnormal Physical Examination Values | Day 1 and Day 15 of each cycle through 30 (+/- 7) days after last dose (up to 5 years and 2 months) | A complete physical examination, vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, temperature, and respiratory rate), and weight were performed pre-specified time points for Phase 1A. During the treatment period, symptom-directed physical examinations were performed. If there were no complaints and no abnormal findings from the previous visit for a particular organ system, a physical examination of that organ system was not required. |
| Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings | Day 15 of cycle 1, Day 1 of Cycle 2 and all additional cycles, and 30 (+/- 7) days after last dose (up to 5 years and 2 months) | Ophthalmological examinations (such as eyesight/visual acuity, fundoscopy, slit lamp microscopy, and optical coherence tomography \[or equivalent diagnostic test\]) were performed at pre-specified time points for Phase 1A. Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) will be assessed by an appropriate specialist at Screening. Participants dosed underwent subsequent ophthalmologic examinations, a specified in the protocol, by an appropriate specialist during study treatment. |
| Phase 1A: Number Of Participants With Abnormal Electrocardiograms | Days 1 and 15 of cycle 1; Day 1 of cycle 2 and all additional cycles; Day 1 of cycle 4; 30 (+/- 7) days after last dose (up to 5 years and 2 months) | Electrocardiograms were obtained at pre-specified time points. Significant QT interval corrected for heart rate (QTc) prolongation was defined as an interval ≥ 500 milliseconds (msec) or an interval which increases by ≥ 60 msec over baseline. |
| Phase 1A: Number Of Participants With Abnormal Laboratory Values | Day -28 (predose), Days 1, 8, and 15 of cycle 1; Days 1 and 15 of cycle 2 and additional cycles; Days 1 and 15 of cycle 4; 30 (+/- 7) days after last dose (up to 5 years and 2 months) | Clinical chemistry, hematology, coagulation, and urinalysis were performed at pre-specified time points for Phase 1A. If warranted, additional testing was done, or the relevant tests done more frequently in accordance with institutional guidelines. All participants who had any Grade 3 or Grade 4 laboratory abnormalities at withdrawal from the study were followed up until they had returned to Grade 1 or Grade 2, unless these were not likely to improve due to the underlying disease. Participants experiencing decreases (low) and increases (high) to ≥ Grade 3 are reported. |
| Phase 1A: Number Of Participants Experiencing Severe AEs | Day -28 through 5 years and 2 months | All AEs were monitored per the NCI-CTCAE (v 4.03 2010). In addition to performing the CTCAE assessment, the intensity of each AE and serious adverse event (SAE) recorded was assigned to one of the following categories based on the Investigator's clinical judgment: Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate: An event that is sufficiently discomforting to interfere with normal everyday activities; severe: An event that prevents normal everyday activities. Severity was a category utilized for rating the intensity of an event and, accordingly, both AEs and SAEs could be assessed as severe. |
| Phase 1B: Objective Response Rate (ORR) | Day -28 through 5 years and 2 months | The ORR was defined as the percentage of participants in the study whose best overall response was either complete response (CR) or partial response (PR) as assessed by investigators based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1A: CR Rate | Day -28 through 5 years and 2 months | The CR rate was based on RECIST v 1.1 and the results of Investigator evaluations. |
| Phase 1A: PR Rate | Day -28 through 5 years and 2 months | The PR rate was based on RECIST v 1.1 and the results of Investigator evaluations. |
| Phase 1A: Stable Disease (SD) Rate | Day -28 through 5 years and 2 months | The SD rate was based on RECIST v 1.1 and the results of Investigator evaluations. |
| Phase 1A: Progression-free Survival (PFS) | Day -28 through 5 years and 2 months | PFS was defined as the time from the date of first study dose to disease progression or death whichever occurs first. Participants without an event (no disease progression or death) were censored at the date of last tumor assessment. Participants with no baseline or post-baseline tumor assessments were censored at Day 1. PFS was based on RECIST v 1.1 and the results of Investigator evaluations. |
| Phase 1A: Overall Survival (OS) | Day -28 through 5 years and 2 months | OS was defined as the time interval between the date of the first study drug dose to the date of death for any cause. Kaplan-Meier methodology was used to estimate OS at various time points. The OS was based on RECIST v 1.1 and the results of Investigator evaluations. |
| Phase 1A: Duration Of Response (DOR) | Day -28 through 5 years and 2 months | DOR for responders (CR or PR) was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease or death for any cause, whichever occurred earlier. For participants who were alive without progression following the qualifying response, DOR was censored on the date of last evaluable tumor assessment or last follow-up for progression of disease. The DOR was based on RECIST v 1.1 and the results of Investigator evaluations. |
| Phase 1B: Number of Participants Experiencing AEs | Day -28 through 5 years and 2 months | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product. All AEs were monitored per the NCI-CTCAE (v 4.03 2010). |
| Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Pre-dose, Day 1 Cycle 5 and every other Cycle in the first 6 months, every 4 cycles in the next 6 months, once every 6 months up to end of treatment (up to 5 years and 2 months) | — |
| Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab | Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose | — |
| Phase 1B: Disease Control Rate (DCR) | Day -28 through 5 years and 2 months | The DCR was defined as the percentage of participants who achieve CR, PR, and SD based on RECIST v 1.1 in participants with select tumor types. |
| Phase 1B: Clinical Benefit Rate (CBR) | Day -28 through 5 years and 2 months | The CBR was defined as the percentage of participants who achieved CR, PR, and durable SD \[SD ≥24 weeks\] based on RECIST v 1.1 in participants with select tumor types. |
| Phase 1B: Number Of Participants With Abnormal Physical Examination Values | Day -28 (predose), Days 1, 4, 8, and 15 of cycle 1; Day 1 of cycle 2; through 30 (+/- 7) days after last dose up to 5 years and 2 months | A complete physical examination, vital signs (SBP, DBP, pulse rate, temperature, and respiratory rate), and weight were performed pre-specified time points for Phase 1B. During the treatment period, symptom-directed physical examinations were performed. If there were no complaints and no abnormal findings from the previous visit for a particular organ system, a physical examination of that organ system was not required. |
| Phase 1B: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings | Day -28 (predose), Day 1 of cycle 2 and additional cycles, and 30 (+/- 7) days after last dose up to 5 years and 2 months | Ophthalmological examinations (such as eyesight/visual acuity, fundoscopy, slit lamp microscopy, and optical coherence tomography \[or equivalent diagnostic test\]) were performed at pre-specified time points for Phase 1B. Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) will be assessed by an appropriate specialist at Screening. Participants dosed underwent subsequent ophthalmologic examinations, a specified in the protocol, by an appropriate specialist during study treatment. |
| Phase 1B: Number Of Participants With Abnormal Electrocardiograms | Day -28 (predose), Days 1 and 15 of cycle 1; Day 1 of cycle 2 and additional cycles; 30 (+/- 7) days after last dose up to 5 years and 2 months | Electrocardiograms were obtained at pre-specified time points. Significant QTc prolongation was defined as an interval ≥ 500 msec or an interval which increases by ≥ 60 msec over baseline. |
| Phase 1B: Number Of Participants With Abnormal Laboratory Values | Day -28 (predose), Days 1, 8, and 15 of cycle 1; Day 1 of cycle 2 and additional cycles; 30 (+/- 7) days after last dose up to 5 years and 2 months | Clinical chemistry, hematology, coagulation, and urinalysis will be performed at pre-specified time points for Phase 1A and Phase 1B respectively. If warranted, additional testing was done, or the relevant tests done more frequently in accordance with institutional guidelines. All participants who had any Grade 3 or Grade 4 laboratory abnormalities at withdrawal from the study were followed up until they had returned to Grade 1 or Grade 2, unless these were not likely to improve due to the underlying disease. Participants experiencing decreases (low) and increases (high) to ≥ Grade 3 are reported. |
| Phase 1B: Number Of Participants Experiencing Severe AEs | Day -28 through 5 years and 2 months | All AEs were monitored per the NCI-CTCAE (v 4.03 2010). In addition to performing the CTCAE assessment, the intensity of each AE and SAE recorded was assigned to one of the following categories based on the Investigator's clinical judgment: Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate: An event that is sufficiently discomforting to interfere with normal everyday activities; severe: An event that prevents normal everyday activities. Severity was a category utilized for rating the intensity of an event and, accordingly, both AEs and SAEs could be assessed as severe. |
| Phase 1B: PFS | Day -28 through 5 years and 2 months | PFS was defined as the time from the date of first study dose to disease progression or death whichever occurs first. Participants without an event (no disease progression or death) were censored at the date of last tumor assessment. Participants with no baseline or post-baseline tumor assessments were censored at Day 1. PFS was based on RECIST v 1.1 and the results of Investigator evaluations. |
| Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab | Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose | — |
| Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab | Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose | — |
| Phase 1A: Half-life (T½) For Tislelizumab | Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose | — |
| Phase 1A - Part 3: Clearance (Cl) For Tislelizumab | Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose | — |
| Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) | Day 1 of Cycles 1 through 15 | Immunogenicity was summarized by the number and percentage of participants who developed detectable treatment-emergent ADAs, which included positive ADAs and neutralizing antibodies (NAb). |
| Phase 1A: ORR | Day -28 through 5 years and 2 months | The ORR was defined as the percentage of participants in the study whose best overall response was either CR or PR as assessed by investigators based on RECIST v 1.1. |
Countries
Australia, New Zealand, South Korea, Taiwan, United States
Participant flow
Recruitment details
This study was conducted in 27 centers in 5 countries, enrolled from June 2015 to October 2017 across both Phases, and was initiated in June 2015. After a 5-year period the sponsor decided to close the study as primary and secondary endpoints were met. Participants still on treatment were rolled into a separate long-term extension study (BGB-A317-290-LTE1) to continue treatment.
Participants by arm
| Arm | Count |
|---|---|
| BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg Participants were dosed at 0.5 milligrams/kilograms (mg/kg), once every 2 weeks (Q2W) until death, disease progression, unacceptable toxicities, or withdrawal of consent.. Each treatment cycle was 28 days in duration. | 3 |
| BGB-A317 Phase 1A - Part 1 - 2.0 mg/kg Participants were dosed at 2.0 mg/kg, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration | 26 |
| BGB-A317 Phase 1A - Part 1 - 5.0 mg/kg Participants were dosed at 5.0 mg/kg, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent.. Each treatment cycle was 28 days in duration | 26 |
| BGB-A317 Phase 1A - Part 1 - 10.0 mg/kg Participants were dosed at 10.0 mg/kg, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | 7 |
| BGB-A317 Phase 1A - Part 2 - 2.0 mg/kg Participants received selected dosing based on Part 1 of 2.0 mg/kg once every 3 weeks (Q3W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | 21 |
| BGB-A317 Phase 1A - Part 2 - 5.0 mg/kg Participants received selected dosing based on Part 1 of 5.0 mg/kg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | 20 |
| BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg Participants received selected maximum tolerated dose of 200.0 mg/kg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | 13 |
| BGB-A317 Phase 1B Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, subject discontinuation/ withdrawal or at the discretion of the Investigator in consultation with Sponsor, as determined by the safety monitoring committee, in 9 indication expansion Arms. Each treatment cycle was 21 days in duration. | 335 |
| Total | 451 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 22 | 23 | 7 | 17 | 16 | 10 | 248 |
| Overall Study | Logistics | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 17 |
| Overall Study | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Rolled into long-term extension study | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 1 | 3 | 3 | 0 | 3 | 4 | 3 | 37 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 30 |
Baseline characteristics
| Characteristic | BGB-A317 Phase 1A - Part 1 - 2.0 mg/kg | BGB-A317 Phase 1A - Part 1 - 5.0 mg/kg | BGB-A317 Phase 1A - Part 1 - 10.0 mg/kg | BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg | BGB-A317 Phase 1A - Part 2 - 2.0 mg/kg | BGB-A317 Phase 1A - Part 2 - 5.0 mg/kg | BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg | BGB-A317 Phase 1B | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 11.15 | 57.8 years STANDARD_DEVIATION 13.32 | 57.1 years STANDARD_DEVIATION 8.13 | 54.7 years STANDARD_DEVIATION 7.02 | 63.6 years STANDARD_DEVIATION 10.09 | 62.6 years STANDARD_DEVIATION 11.14 | 58.4 years STANDARD_DEVIATION 17.76 | 59.5 years STANDARD_DEVIATION 11.92 | 59.6 years STANDARD_DEVIATION 11.96 |
| Age, Customized < 65 Years | 18 Participants | 16 Participants | 6 Participants | 3 Participants | 8 Participants | 11 Participants | 6 Participants | 217 Participants | 285 Participants |
| Age, Customized ≥ 65 Years | 8 Participants | 10 Participants | 1 Participants | 0 Participants | 13 Participants | 9 Participants | 7 Participants | 118 Participants | 166 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 26 Participants | 7 Participants | 3 Participants | 21 Participants | 20 Participants | 13 Participants | 322 Participants | 436 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 120 Participants | 130 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Chinese (enrolled from Taiwan sites) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 61 Participants | 61 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Non-Chinese | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 59 Participants | 69 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 18 Participants | 23 Participants |
| Race/Ethnicity, Customized White | 22 Participants | 23 Participants | 7 Participants | 3 Participants | 19 Participants | 16 Participants | 11 Participants | 189 Participants | 290 Participants |
| Sex: Female, Male Female | 12 Participants | 15 Participants | 4 Participants | 3 Participants | 10 Participants | 12 Participants | 5 Participants | 144 Participants | 205 Participants |
| Sex: Female, Male Male | 14 Participants | 11 Participants | 3 Participants | 0 Participants | 11 Participants | 8 Participants | 8 Participants | 191 Participants | 246 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 97 / 116 | 249 / 335 |
| other Total, other adverse events | 112 / 116 | 302 / 335 |
| serious Total, serious adverse events | 40 / 116 | 131 / 335 |
Outcome results
Primary
Phase 1A: Number of Participants Experiencing Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product. All AEs were monitored per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version \[v\] 4.03 2010).
Time frame: Day -28 through 5 years and 2 months
Population: Safety Analysis Set (SAF) included all participants who had received any dose of tislelizumab. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Number of Participants Experiencing Adverse Events (AEs) | 114 Participants |
Primary
Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings
Ophthalmological examinations (such as eyesight/visual acuity, fundoscopy, slit lamp microscopy, and optical coherence tomography \[or equivalent diagnostic test\]) were performed at pre-specified time points for Phase 1A. Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) will be assessed by an appropriate specialist at Screening. Participants dosed underwent subsequent ophthalmologic examinations, a specified in the protocol, by an appropriate specialist during study treatment.
Time frame: Day 15 of cycle 1, Day 1 of Cycle 2 and all additional cycles, and 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Population: Safety Analysis Set (SAF) included all participants who had received any dose of tislelizumab. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings | 0 Participants |
Primary
Phase 1A: Number Of Participants Experiencing Severe AEs
All AEs were monitored per the NCI-CTCAE (v 4.03 2010). In addition to performing the CTCAE assessment, the intensity of each AE and serious adverse event (SAE) recorded was assigned to one of the following categories based on the Investigator's clinical judgment: Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate: An event that is sufficiently discomforting to interfere with normal everyday activities; severe: An event that prevents normal everyday activities. Severity was a category utilized for rating the intensity of an event and, accordingly, both AEs and SAEs could be assessed as severe.
Time frame: Day -28 through 5 years and 2 months
Population: Safety Analysis Set (SAF) included all participants who had received any dose of tislelizumab. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants Experiencing Severe AEs | 14 Participants |
Primary
Phase 1A: Number Of Participants With Abnormal Electrocardiograms
Electrocardiograms were obtained at pre-specified time points. Significant QT interval corrected for heart rate (QTc) prolongation was defined as an interval ≥ 500 milliseconds (msec) or an interval which increases by ≥ 60 msec over baseline.
Time frame: Days 1 and 15 of cycle 1; Day 1 of cycle 2 and all additional cycles; Day 1 of cycle 4; 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Population: Safety Analysis Set: all participants who had received any dose of tislelizumab. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QT corrected using Fridericia's formula (QTcF) Interval measure of >450 msec | 31 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure of > 480 msec | 9 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure of > 500 msec | 3 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure ≤ 30 msec increase from baseline | 73 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure ≤ 30 and ≤ 60 msec increase from baseline | 35 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure > 60 msec increase from baseline | 8 Participants |
Primary
Phase 1A: Number Of Participants With Abnormal Laboratory Values
Clinical chemistry, hematology, coagulation, and urinalysis were performed at pre-specified time points for Phase 1A. If warranted, additional testing was done, or the relevant tests done more frequently in accordance with institutional guidelines. All participants who had any Grade 3 or Grade 4 laboratory abnormalities at withdrawal from the study were followed up until they had returned to Grade 1 or Grade 2, unless these were not likely to improve due to the underlying disease. Participants experiencing decreases (low) and increases (high) to ≥ Grade 3 are reported.
Time frame: Day -28 (predose), Days 1, 8, and 15 of cycle 1; Days 1 and 15 of cycle 2 and additional cycles; Days 1 and 15 of cycle 4; 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Population: Safety Analysis Set: participants who had received any dose of tislelizumab and with baseline assessment and at least one post-baseline assessment. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Albumin: Low | 11 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Alanine Aminotransferase: High | 6 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Alkaline Phosphatase: High | 7 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Aspartate Aminotransferase: High | 5 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Bilirubin: High | 7 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Calcium: Low | 7 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Calcium: High | 2 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Creatinine: High | 6 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Glucose: Low | 5 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Glucose: High | 13 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Hemoglobin: Low | 6 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Leukocytes: Low | 3 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Leukocytes: High | 0 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Lymphocytes: Low | 22 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Lymphocytes: High | 2 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Neutrophils: Low | 2 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Phosphate: Low | 19 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Platelets: Low | 1 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Potassium: Low | 21 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Potassium: High | 7 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Sodium: Low | 8 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Laboratory Values | Sodium: High | 0 Participants |
Primary
Phase 1A: Number Of Participants With Abnormal Physical Examination Values
A complete physical examination, vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, temperature, and respiratory rate), and weight were performed pre-specified time points for Phase 1A. During the treatment period, symptom-directed physical examinations were performed. If there were no complaints and no abnormal findings from the previous visit for a particular organ system, a physical examination of that organ system was not required.
Time frame: Day 1 and Day 15 of each cycle through 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Population: Safety Analysis Set: all participants who had received any dose of tislelizumab. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline pulse rate measure ≤ 45 beats per minute (bpm) | 1 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline pulse rate measure ≥ 120 bpm | 6 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline SBP measure ≤ 60 millimeters of mercury (mmHg) | 0 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline SBP measure ≤ 90 mmHg | 9 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline SBP measure ≥ 160 mmHg | 17 Participants |
| BGB-A317 Phase 1A | Phase 1A: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline DBP measure ≥ 100 mmHg | 5 Participants |
Primary
Phase 1B: Objective Response Rate (ORR)
The ORR was defined as the percentage of participants in the study whose best overall response was either complete response (CR) or partial response (PR) as assessed by investigators based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set (EFF) included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Objective Response Rate (ORR) | 11.6 percentage of participants |
Secondary
Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs)
Immunogenicity was summarized by the number and percentage of participants who developed detectable treatment-emergent ADAs, which included positive ADAs and neutralizing antibodies (NAb).
Time frame: Day 1 of Cycles 1 through 15
Population: Evaluable set: participants who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) | 1 Participants |
| BGB-A317 Phase 1A - Part 1 - 2.0 mg/kg | Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) | 6 Participants |
| BGB-A317 Phase 1A - Part 1 - 5.0 mg/kg | Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) | 5 Participants |
| BGB-A317 Phase 1A - Part 1 - 10.0 mg/kg | Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) | 1 Participants |
| BGB-A317 Phase 1A - Part 2 - 2.0 mg/kg | Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) | 6 Participants |
| BGB-A317 Phase 1A - Part 2 - 5.0 mg/kg | Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) | 43 Participants |
| BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg | Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) | 3 Participants |
Secondary
Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Population: PK Analysis Set (PKS) included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab | 84.92 micrograms/milliliter*day | Standard Deviation 35.9 |
| BGB-A317 Phase 1A - Part 1 - 2.0 mg/kg | Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab | 332.2 micrograms/milliliter*day | Standard Deviation 57.33 |
| BGB-A317 Phase 1A - Part 1 - 5.0 mg/kg | Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab | 811.8 micrograms/milliliter*day | Standard Deviation 239.5 |
| BGB-A317 Phase 1A - Part 1 - 10.0 mg/kg | Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab | 1916.0 micrograms/milliliter*day | Standard Deviation 458.5 |
| BGB-A317 Phase 1A - Part 2 - 2.0 mg/kg | Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab | 512.1 micrograms/milliliter*day | Standard Deviation 122.2 |
| BGB-A317 Phase 1A - Part 2 - 5.0 mg/kg | Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab | 1219.0 micrograms/milliliter*day | Standard Deviation 287.4 |
| BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg | Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab | 674.7 micrograms/milliliter*day | Standard Deviation 173.6 |
Secondary
Phase 1A: CR Rate
The CR rate was based on RECIST v 1.1 and the results of Investigator evaluations.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: CR Rate | 6 Participants |
Secondary
Phase 1A: Duration Of Response (DOR)
DOR for responders (CR or PR) was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease or death for any cause, whichever occurred earlier. For participants who were alive without progression following the qualifying response, DOR was censored on the date of last evaluable tumor assessment or last follow-up for progression of disease. The DOR was based on RECIST v 1.1 and the results of Investigator evaluations.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Duration Of Response (DOR) | 14.6 months |
Secondary
Phase 1A: Half-life (T½) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Population: PKS included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Half-life (T½) For Tislelizumab | 10.7 hours | Standard Deviation 3.9 |
| BGB-A317 Phase 1A - Part 1 - 2.0 mg/kg | Phase 1A: Half-life (T½) For Tislelizumab | 12.9 hours | Standard Deviation 1.2 |
| BGB-A317 Phase 1A - Part 1 - 5.0 mg/kg | Phase 1A: Half-life (T½) For Tislelizumab | 15.0 hours | Standard Deviation 14.4 |
| BGB-A317 Phase 1A - Part 1 - 10.0 mg/kg | Phase 1A: Half-life (T½) For Tislelizumab | 14.5 hours | Standard Deviation 4.04 |
| BGB-A317 Phase 1A - Part 2 - 2.0 mg/kg | Phase 1A: Half-life (T½) For Tislelizumab | 17.1 hours | Standard Deviation 8.14 |
| BGB-A317 Phase 1A - Part 2 - 5.0 mg/kg | Phase 1A: Half-life (T½) For Tislelizumab | 19.6 hours | Standard Deviation 7.63 |
| BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg | Phase 1A: Half-life (T½) For Tislelizumab | 16.8 hours | Standard Deviation 5.5 |
Secondary
Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Population: PKS included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab | 13.5 micrograms/milliliter | Standard Deviation 3.8 |
| BGB-A317 Phase 1A - Part 1 - 2.0 mg/kg | Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab | 48.3 micrograms/milliliter | Standard Deviation 6.89 |
| BGB-A317 Phase 1A - Part 1 - 5.0 mg/kg | Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab | 147.0 micrograms/milliliter | Standard Deviation 50.8 |
| BGB-A317 Phase 1A - Part 1 - 10.0 mg/kg | Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab | 278.0 micrograms/milliliter | Standard Deviation 53.7 |
| BGB-A317 Phase 1A - Part 2 - 2.0 mg/kg | Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab | 56.8 micrograms/milliliter | Standard Deviation 12.8 |
| BGB-A317 Phase 1A - Part 2 - 5.0 mg/kg | Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab | 130.0 micrograms/milliliter | Standard Deviation 29.7 |
| BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg | Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab | 77.2 micrograms/milliliter | Standard Deviation 13.9 |
Secondary
Phase 1A: ORR
The ORR was defined as the percentage of participants in the study whose best overall response was either CR or PR as assessed by investigators based on RECIST v 1.1.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: ORR | 18.1 percentage of participants |
Secondary
Phase 1A: Overall Survival (OS)
OS was defined as the time interval between the date of the first study drug dose to the date of death for any cause. Kaplan-Meier methodology was used to estimate OS at various time points. The OS was based on RECIST v 1.1 and the results of Investigator evaluations.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Overall Survival (OS) | 13.6 months |
Secondary
Phase 1A - Part 3: Clearance (Cl) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Population: PK Analysis Set (PKS) included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing. per-pre-specification, data was analyzed only for Part 3 of Phase 1A.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A - Part 3: Clearance (Cl) For Tislelizumab | 0.186 liters/day |
Secondary
Phase 1A: Progression-free Survival (PFS)
PFS was defined as the time from the date of first study dose to disease progression or death whichever occurs first. Participants without an event (no disease progression or death) were censored at the date of last tumor assessment. Participants with no baseline or post-baseline tumor assessments were censored at Day 1. PFS was based on RECIST v 1.1 and the results of Investigator evaluations.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date.The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Progression-free Survival (PFS) | 3.5 months |
Secondary
Phase 1A: PR Rate
The PR rate was based on RECIST v 1.1 and the results of Investigator evaluations.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: PR Rate | 15 Participants |
Secondary
Phase 1A: Stable Disease (SD) Rate
The SD rate was based on RECIST v 1.1 and the results of Investigator evaluations.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date. The analysis was pre-specified to be a pooled analysis of all Part 1A cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Stable Disease (SD) Rate | 42 Participants |
Secondary
Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Population: PKS included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab | 3.46 hours | Standard Deviation 3.12 |
| BGB-A317 Phase 1A - Part 1 - 2.0 mg/kg | Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab | 2.39 hours | Standard Deviation 0.89 |
| BGB-A317 Phase 1A - Part 1 - 5.0 mg/kg | Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab | 2.48 hours | Standard Deviation 0.73 |
| BGB-A317 Phase 1A - Part 1 - 10.0 mg/kg | Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab | 2.43 hours | Standard Deviation 1.83 |
| BGB-A317 Phase 1A - Part 2 - 2.0 mg/kg | Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab | 1.57 hours | Standard Deviation 0.65 |
| BGB-A317 Phase 1A - Part 2 - 5.0 mg/kg | Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab | 4.95 hours | Standard Deviation 15.4 |
| BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg | Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab | 1.40 hours | Standard Deviation 0.82 |
Secondary
Phase 1B: Clinical Benefit Rate (CBR)
The CBR was defined as the percentage of participants who achieved CR, PR, and durable SD \[SD ≥24 weeks\] based on RECIST v 1.1 in participants with select tumor types.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Clinical Benefit Rate (CBR) | 24.5 percentage of participants |
Secondary
Phase 1B: Disease Control Rate (DCR)
The DCR was defined as the percentage of participants who achieve CR, PR, and SD based on RECIST v 1.1 in participants with select tumor types.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Disease Control Rate (DCR) | 41.2 percentage of participants |
Secondary
Phase 1B: Number of Participants Experiencing AEs
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product. All AEs were monitored per the NCI-CTCAE (v 4.03 2010).
Time frame: Day -28 through 5 years and 2 months
Population: Safety Analysis Set (SAF) included all patients who had received any dose of tislelizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Number of Participants Experiencing AEs | 322 Participants |
Secondary
Phase 1B: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings
Ophthalmological examinations (such as eyesight/visual acuity, fundoscopy, slit lamp microscopy, and optical coherence tomography \[or equivalent diagnostic test\]) were performed at pre-specified time points for Phase 1B. Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) will be assessed by an appropriate specialist at Screening. Participants dosed underwent subsequent ophthalmologic examinations, a specified in the protocol, by an appropriate specialist during study treatment.
Time frame: Day -28 (predose), Day 1 of cycle 2 and additional cycles, and 30 (+/- 7) days after last dose up to 5 years and 2 months
Population: Safety Analysis Set (SAF) included all patients who had received any dose of tislelizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings | 0 Participants |
Secondary
Phase 1B: Number Of Participants Experiencing Severe AEs
All AEs were monitored per the NCI-CTCAE (v 4.03 2010). In addition to performing the CTCAE assessment, the intensity of each AE and SAE recorded was assigned to one of the following categories based on the Investigator's clinical judgment: Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate: An event that is sufficiently discomforting to interfere with normal everyday activities; severe: An event that prevents normal everyday activities. Severity was a category utilized for rating the intensity of an event and, accordingly, both AEs and SAEs could be assessed as severe.
Time frame: Day -28 through 5 years and 2 months
Population: Safety Analysis Set (SAF) included all patients who had received any dose of tislelizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants Experiencing Severe AEs | 27 Participants |
Secondary
Phase 1B: Number Of Participants With Abnormal Electrocardiograms
Electrocardiograms were obtained at pre-specified time points. Significant QTc prolongation was defined as an interval ≥ 500 msec or an interval which increases by ≥ 60 msec over baseline.
Time frame: Day -28 (predose), Days 1 and 15 of cycle 1; Day 1 of cycle 2 and additional cycles; 30 (+/- 7) days after last dose up to 5 years and 2 months
Population: Safety Analysis Set: all participants who had received any dose of tislelizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure > 450 msec | 84 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure > 480 msec | 24 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure > 500 msec | 10 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure ≤ 30 msec increase from baseline | 241 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure >30 and ≤ 60 msec increase from baseline | 67 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Electrocardiograms | At least 1 postbaseline QTcF Interval measure > 60 msec increase | 22 Participants |
Secondary
Phase 1B: Number Of Participants With Abnormal Laboratory Values
Clinical chemistry, hematology, coagulation, and urinalysis will be performed at pre-specified time points for Phase 1A and Phase 1B respectively. If warranted, additional testing was done, or the relevant tests done more frequently in accordance with institutional guidelines. All participants who had any Grade 3 or Grade 4 laboratory abnormalities at withdrawal from the study were followed up until they had returned to Grade 1 or Grade 2, unless these were not likely to improve due to the underlying disease. Participants experiencing decreases (low) and increases (high) to ≥ Grade 3 are reported.
Time frame: Day -28 (predose), Days 1, 8, and 15 of cycle 1; Day 1 of cycle 2 and additional cycles; 30 (+/- 7) days after last dose up to 5 years and 2 months
Population: Safety Analysis Set: participants who had received any dose of tislelizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Alanine Aminotransferase: High | 21 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Albumin: Low | 42 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Alkaline Phosphatase: High | 21 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Aspartate Aminotransferase: High | 21 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Bilirubin: High | 22 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Calcium: Low | 12 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Calcium: High | 7 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Creatinine: High | 20 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Glucose: Low | 8 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Glucose: High | 32 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Hemoglobin: Low | 19 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Leukocytes: Low | 8 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Leukocytes: High | 1 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Lymphocytes: Low | 33 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Lymphocytes: High | 2 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Neutrophils: Low | 5 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Phosphate: Low | 42 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Platelets: Low | 3 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Potassium: Low | 35 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Potassium: High | 4 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Sodium: Low | 25 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Laboratory Values | Sodium: High | 1 Participants |
Secondary
Phase 1B: Number Of Participants With Abnormal Physical Examination Values
A complete physical examination, vital signs (SBP, DBP, pulse rate, temperature, and respiratory rate), and weight were performed pre-specified time points for Phase 1B. During the treatment period, symptom-directed physical examinations were performed. If there were no complaints and no abnormal findings from the previous visit for a particular organ system, a physical examination of that organ system was not required.
Time frame: Day -28 (predose), Days 1, 4, 8, and 15 of cycle 1; Day 1 of cycle 2; through 30 (+/- 7) days after last dose up to 5 years and 2 months
Population: Safety Analysis Set: all participants who had received any dose of tislelizumab and with baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline pulse rate measure ≤ 45 bpm | 5 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline pulse rate measure ≥ 120 bpm | 26 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline SBP measure ≤ 60 mmHg | 1 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline SBP measure ≤ 90 mmHg | 24 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline SBP measure ≥ 160 mmHg | 30 Participants |
| BGB-A317 Phase 1A | Phase 1B: Number Of Participants With Abnormal Physical Examination Values | At least one postbaseline DBP measure ≥ 100 mmHg | 12 Participants |
Secondary
Phase 1B: PFS
PFS was defined as the time from the date of first study dose to disease progression or death whichever occurs first. Participants without an event (no disease progression or death) were censored at the date of last tumor assessment. Participants with no baseline or post-baseline tumor assessments were censored at Day 1. PFS was based on RECIST v 1.1 and the results of Investigator evaluations.
Time frame: Day -28 through 5 years and 2 months
Population: Efficacy Evaluable Set included all participants in the SAF with measurable disease at baseline per RECIST v 1.1 who had at least 1 evaluable post-baseline tumor assessment, unless discontinued due to clinical disease progression, or death within 10 weeks of the first dose date.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: PFS | 2.1 months |
Secondary
Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab
Time frame: Pre-dose, Day 1 Cycle 5 and every other Cycle in the first 6 months, every 4 cycles in the next 6 months, once every 6 months up to end of treatment (up to 5 years and 2 months)
Population: PK Analysis Set included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Non-Small Cell Lung Cancer | 63.9 micrograms/milliliter | Geometric Coefficient of Variation 47.8 |
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Ovarian Cancer | 90.4 micrograms/milliliter | Geometric Coefficient of Variation 66.7 |
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Gastric Cancer | 40.7 micrograms/milliliter | Geometric Coefficient of Variation 91.4 |
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Hepatocellular Carcinoma | 54.4 micrograms/milliliter | Geometric Coefficient of Variation 56.8 |
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Head & Neck Squamous Cell Carcinoma | 77.4 micrograms/milliliter | Geometric Coefficient of Variation 45.8 |
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Esophageal Carcinoma | 57.8 micrograms/milliliter | Geometric Coefficient of Variation 62.4 |
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Triple Negative Breast Cancer | 47.8 micrograms/milliliter | Geometric Coefficient of Variation 78.9 |
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Cholangio Carcinoma | 65.7 micrograms/milliliter | Geometric Coefficient of Variation 47.9 |
| BGB-A317 Phase 1A | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab | Other Solid Tumors | 80.4 micrograms/milliliter | Geometric Coefficient of Variation 43.5 |