Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors
Sponsor
BeiGene (Industry)
Overall Status
Completed
CT.gov ID
NCT02407990
Collaborator
(none)
451
27
2
62.4
16.7
0.3
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
451 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1A/1B, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activities of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Subjects With Advanced Tumors
Actual Study Start Date
:
Jun 2, 2015
Actual Primary Completion Date
:
Aug 12, 2020
Actual Study Completion Date
:
Aug 12, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BGB-A317 Phase 1A
|
Biological: BGB-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.
|
| Experimental: BGB-A317 Phase 1B
|
Biological: BGB-A317
Participants were assigned to different groups based on their tumor types
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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.
- 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 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 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Participants must have had a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy was available.
-
For Phase 1A: no specific restriction
-
For Phase 1B: histology specified below:
- 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
- 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
-
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.
-
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).
-
Participants must have had measurable disease as defined per Response Evaluation Criteria in Solid Tumor Version 1.1.
-
Eastern Cooperative Oncology Group performance status of ≤ 1.
-
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:
-
History of severe hypersensitivity reactions to other Monoclonal antibodies.
-
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.
-
Prior therapies targeting PD-1 or PD-L1.
-
Participants who failed to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers.
-
Participants with active autoimmune diseases or history of autoimmune diseases should have been excluded.
-
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.
-
Had history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
-
Known history of human immunodeficiency virus.
-
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
- 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/Exclusion criteria may have applied.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 2 | Oncology Consultants, P.A. | Houston | Texas | United States | 77024-2545 |
| 3 | Chris O'Brien Lifehouse | Camperdown | New South Wales | Australia | 2050 |
| 4 | Prince of Wales Hospital | Sydney | New South Wales | Australia | |
| 5 | Tasman Oncology Research Ltd | Southport | Queensland | Australia | 4216 |
| 6 | Princess Alexandra Hospital | Woolloongabba | Queensland | Australia | 4102 |
| 7 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | |
| 8 | The Queen Elizabeth Hospital | Woodville South | South Australia | Australia | |
| 9 | Monash Health | Clayton | Victoria | Australia | |
| 10 | Peter MacCallum Cancer Centre | East Melbourne | Victoria | Australia | |
| 11 | Austin Health Hospital | Heidelberg | Victoria | Australia | |
| 12 | Cabrini Hospital | Malvern | Victoria | Australia | 3144 |
| 13 | Nucleus Network | Melbourne | Victoria | Australia | 3004 |
| 14 | Royal Melbourne Hospital | Melbourne | Victoria | Australia | |
| 15 | Linear Clinical Research/Sir Charles Gairdner Hospital | Nedlands | Western Australia | Australia | |
| 16 | Seoul National University Bundang Hospital | Seongnam | Kyeonggi-do | Korea, Republic of | 13620 |
| 17 | Seoul National University Hospital | Seoul | Korea, Republic of | 3080 | |
| 18 | Asan Medical Center | Seoul | Korea, Republic of | 5505 | |
| 19 | Auckland City Hospital | Grafton | New Zealand | 1023 | |
| 20 | Waikato | Hamilton | New Zealand | 3204 | |
| 21 | Wellington Hospital | Wellington | New Zealand | 6022 | |
| 22 | Kaohsiung Chang Gung Memorial Hospital | Kaohsiung | Taiwan | 83301 | |
| 23 | National Cheng Kung University Hospital | Tainan | Taiwan | 704 | |
| 24 | Taipei Veterans General Hospital | Taipei | Taiwan | 11217 | |
| 25 | National Taiwan University Hospital | Taipei | Taiwan | ||
| 26 | Linkou Chang Gung Memorial Hospital | Taoyuan | Taiwan | 33305 | |
| 27 | Chang Gung Memorial Hospital, Sachin | Taoyuan | Taiwan | 61363 |
Sponsors and Collaborators
- BeiGene
Investigators
- Principal Investigator: Study Director, BeiGene
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
BeiGene
ClinicalTrials.gov Identifier:
NCT02407990
Other Study ID Numbers:
- BGB-A317_Study_001
First Posted:
Apr 3, 2015
Last Update Posted:
Nov 17, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg | 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 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were dosed at 0.5 milligrams/kilograms (mg/kg), tislelizumab, once every 2 weeks (Q2W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 2.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 5.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 10.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants received selected dosing based on Part 1 of 2.0 mg/kg tislelizumab, once every 3 weeks (Q3W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected dosing based on Part 1 of 5.0 mg/kg tislelizumab,Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected maximum tolerated dose of 200.0 mg/kg tislelizumab, Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants were dosed at 5 mg/kg tislelizumab, 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. |
| Period Title: Overall Study | ||||||||
| STARTED | 3 | 26 | 26 | 7 | 21 | 20 | 13 | 335 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 26 | 26 | 7 | 21 | 20 | 13 | 335 |
Baseline Characteristics
| Arm/Group Title | BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg | 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 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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 | 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 | 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. | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 3 | 26 | 26 | 7 | 21 | 20 | 13 | 335 | 451 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [years] |
54.7
(7.02)
|
59.1
(11.15)
|
57.8
(13.32)
|
57.1
(8.13)
|
63.6
(10.09)
|
62.6
(11.14)
|
58.4
(17.76)
|
59.5
(11.92)
|
59.6
(11.96)
|
| Age, Customized (Count of Participants) | |||||||||
| < 65 Years |
3
100%
|
18
69.2%
|
16
61.5%
|
6
85.7%
|
8
38.1%
|
11
55%
|
6
46.2%
|
217
64.8%
|
285
63.2%
|
| ≥ 65 Years |
0
0%
|
8
30.8%
|
10
38.5%
|
1
14.3%
|
13
61.9%
|
9
45%
|
7
53.8%
|
118
35.2%
|
166
36.8%
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
3
100%
|
12
46.2%
|
15
57.7%
|
4
57.1%
|
10
47.6%
|
12
60%
|
5
38.5%
|
144
43%
|
205
45.5%
|
| Male |
0
0%
|
14
53.8%
|
11
42.3%
|
3
42.9%
|
11
52.4%
|
8
40%
|
8
61.5%
|
191
57%
|
246
54.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||
| Hispanic or Latino |
0
0%
|
2
7.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
8
2.4%
|
10
2.2%
|
| Not Hispanic or Latino |
3
100%
|
24
92.3%
|
26
100%
|
7
100%
|
21
100%
|
20
100%
|
13
100%
|
322
96.1%
|
436
96.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
5
1.5%
|
5
1.1%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.3%
|
1
0.2%
|
| Asian |
0
0%
|
2
7.7%
|
3
11.5%
|
0
0%
|
1
4.8%
|
3
15%
|
1
7.7%
|
120
35.8%
|
130
28.8%
|
| Chinese (enrolled from Taiwan sites) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
61
18.2%
|
61
13.5%
|
| Non-Chinese |
0
0%
|
2
7.7%
|
3
11.5%
|
0
0%
|
1
4.8%
|
3
15%
|
1
7.7%
|
59
17.6%
|
69
15.3%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
5
1.5%
|
5
1.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
0.6%
|
2
0.4%
|
| White |
3
100%
|
22
84.6%
|
23
88.5%
|
7
100%
|
19
90.5%
|
16
80%
|
11
84.6%
|
189
56.4%
|
290
64.3%
|
| Other |
0
0%
|
2
7.7%
|
0
0%
|
0
0%
|
1
4.8%
|
1
5%
|
1
7.7%
|
18
5.4%
|
23
5.1%
|
Outcome Measures
| Title | Phase 1A: Number of Participants Experiencing Adverse Events (AEs) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected maximum tolerated dose (MTD), which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Count of Participants [Participants] |
114
3800%
|
| Title | Phase 1A: Number Of Participants With Abnormal Physical Examination Values |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| At least one postbaseline pulse rate measure ≤ 45 beats per minute (bpm) |
1
33.3%
|
| At least one postbaseline pulse rate measure ≥ 120 bpm |
6
200%
|
| At least one postbaseline SBP measure ≤ 60 millimeters of mercury (mmHg) |
0
0%
|
| At least one postbaseline SBP measure ≤ 90 mmHg |
9
300%
|
| At least one postbaseline SBP measure ≥ 160 mmHg |
17
566.7%
|
| At least one postbaseline DBP measure ≥ 100 mmHg |
5
166.7%
|
| Title | Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Count of Participants [Participants] |
0
0%
|
| Title | Phase 1A: Number Of Participants With Abnormal Electrocardiograms |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| At least 1 postbaseline QT corrected using Fridericia's formula (QTcF) Interval measure of >450 msec |
31
1033.3%
|
| At least 1 postbaseline QTcF Interval measure of > 480 msec |
9
300%
|
| At least 1 postbaseline QTcF Interval measure of > 500 msec |
3
100%
|
| At least 1 postbaseline QTcF Interval measure ≤ 30 msec increase from baseline |
73
2433.3%
|
| At least 1 postbaseline QTcF Interval measure ≤ 30 and ≤ 60 msec increase from baseline |
35
1166.7%
|
| At least 1 postbaseline QTcF Interval measure > 60 msec increase from baseline |
8
266.7%
|
| Title | Phase 1A: Number Of Participants With Abnormal Laboratory Values |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Alanine Aminotransferase: High |
6
200%
|
| Albumin: Low |
11
366.7%
|
| Alkaline Phosphatase: High |
7
233.3%
|
| Aspartate Aminotransferase: High |
5
166.7%
|
| Bilirubin: High |
7
233.3%
|
| Calcium: Low |
7
233.3%
|
| Calcium: High |
2
66.7%
|
| Creatinine: High |
6
200%
|
| Glucose: Low |
5
166.7%
|
| Glucose: High |
13
433.3%
|
| Hemoglobin: Low |
6
200%
|
| Leukocytes: Low |
3
100%
|
| Leukocytes: High |
0
0%
|
| Lymphocytes: Low |
22
733.3%
|
| Lymphocytes: High |
2
66.7%
|
| Neutrophils: Low |
2
66.7%
|
| Phosphate: Low |
19
633.3%
|
| Platelets: Low |
1
33.3%
|
| Potassium: Low |
21
700%
|
| Potassium: High |
7
233.3%
|
| Sodium: Low |
8
266.7%
|
| Sodium: High |
0
0%
|
| Title | Phase 1A: Number Of Participants Experiencing Severe AEs |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Count of Participants [Participants] |
14
466.7%
|
| Title | Phase 1B: Objective Response Rate (ORR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| Number (95% Confidence Interval) [percentage of participants] |
11.6
386.7%
|
| Title | Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg | 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 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 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were dosed at 0.5 milligrams/kilograms (mg/kg), tislelizumab, once every 2 weeks (Q2W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 2.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 5.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 10.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants received selected dosing based on Part 1 of 2.0 mg/kg tislelizumab, once every 3 weeks (Q3W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected dosing based on Part 1 of 5.0 mg/kg tislelizumab,Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected maximum tolerated dose of 200.0 mg/kg tislelizumab, Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 3 | 6 | 6 | 6 | 18 | 20 | 12 |
| Mean (Standard Deviation) [micrograms/milliliter*day] |
84.92
(35.90)
|
332.2
(57.33)
|
811.8
(239.5)
|
1916.0
(458.5)
|
512.1
(122.2)
|
1219.0
(287.4)
|
674.7
(173.6)
|
| Title | Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing. |
| Arm/Group Title | BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg | 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 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 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were dosed at 0.5 milligrams/kilograms (mg/kg), tislelizumab, once every 2 weeks (Q2W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 2.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 5.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 10.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants received selected dosing based on Part 1 of 2.0 mg/kg tislelizumab, once every 3 weeks (Q3W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected dosing based on Part 1 of 5.0 mg/kg tislelizumab,Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected maximum tolerated dose of 200.0 mg/kg tislelizumab, Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 3 | 6 | 6 | 6 | 18 | 20 | 12 |
| Mean (Standard Deviation) [micrograms/milliliter] |
13.5
(3.80)
|
48.3
(6.89)
|
147.0
(50.8)
|
278.0
(53.7)
|
56.8
(12.8)
|
130.0
(29.7)
|
77.2
(13.9)
|
| Title | Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing. |
| Arm/Group Title | BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg | 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 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 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were dosed at 0.5 milligrams/kilograms (mg/kg), tislelizumab, once every 2 weeks (Q2W). until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 2.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 5.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 10.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants received selected dosing based on Part 1 of 2.0 mg/kg tislelizumab, once every 3 weeks (Q3W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected dosing based on Part 1 of 5.0 mg/kg tislelizumab,Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected maximum tolerated dose of 200.0 mg/kg tislelizumab, Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 3 | 6 | 6 | 6 | 18 | 20 | 12 |
| Mean (Standard Deviation) [hours] |
3.46
(3.12)
|
2.39
(0.89)
|
2.48
(0.73)
|
2.43
(1.83)
|
1.57
(0.65)
|
4.95
(15.4)
|
1.40
(0.82)
|
| Title | Phase 1A: Half-life (T½) For Tislelizumab |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS included participants who had received at least the first dose of tislelizumab and provided PK samples as per protocol following first dosing. |
| Arm/Group Title | BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg | 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 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 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were dosed at 0.5 milligrams/kilograms (mg/kg), tislelizumab, once every 2 weeks (Q2W) until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 2.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 5.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants were dosed at 10.0 mg/kg tislelizumab, Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. | Participants received selected dosing based on Part 1 of 2.0 mg/kg tislelizumab, once every 3 weeks (Q3W). until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected dosing based on Part 1 of 5.0 mg/kg tislelizumab,Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. | Participants received selected maximum tolerated dose of 200.0 mg/kg tislelizumab, Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 3 | 6 | 6 | 6 | 18 | 20 | 12 |
| Mean (Standard Deviation) [hours] |
10.7
(3.90)
|
12.9
(1.2)
|
15.0
(14.4)
|
14.5
(4.04)
|
17.1
(8.14)
|
19.6
(7.63)
|
16.8
(5.50)
|
| Title | Phase 1A - Part 3: Clearance (Cl) For Tislelizumab |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg |
|---|---|
| Arm/Group Description | Participants received selected maximum tolerated dose of 200.0 mg/kg tislelizumab, Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 12 |
| Geometric Mean (95% Confidence Interval) [liters/day] |
0.186
|
| Title | Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable set: participants who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. |
| Arm/Group Title | BGB-A317 Phase 1A - Part 1 - 0.5 mg/kg | 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 2 - 2.0 mg/kg | BGB-A317 Phase 1A - Part 2 - 5.0 mg/kg and BGB-A317 Phase 1B | BGB-A317 Phase 1A - Part 3 - 200.0 mg/kg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 | 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. | 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. | Phase 1A: 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. Phase 1B; Participants were dosed at 5 mg/kg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent, as determined by the safety monitoring committee, in 9 indication expansion Arms. Each treatment cycle was 21 days in duration. | 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. |
| Measure Participants | 3 | 21 | 25 | 6 | 19 | 285 | 11 |
| Number [Participants] |
1
33.3%
|
6
23.1%
|
5
19.2%
|
1
14.3%
|
6
28.6%
|
43
215%
|
3
23.1%
|
| Title | Phase 1A: ORR |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Number (95% Confidence Interval) [percentage of participants] |
18.1
603.3%
|
| Title | Phase 1A: CR Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Count of Participants [Participants] |
6
200%
|
| Title | Phase 1A: PR Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Count of Participants [Participants] |
15
500%
|
| Title | Phase 1A: Stable Disease (SD) Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Count of Participants [Participants] |
42
1400%
|
| Title | Phase 1A: Progression-free Survival (PFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Median (95% Confidence Interval) [months] |
3.5
|
| Title | Phase 1A: Overall Survival (OS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Median (95% Confidence Interval) [months] |
13.6
|
| Title | Phase 1A: Duration Of Response (DOR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1A |
|---|---|
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which was 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 21 days in duration. |
| Measure Participants | 116 |
| Median (95% Confidence Interval) [months] |
14.6
|
| Title | Phase 1B: Number of Participants Experiencing AEs |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAF) included all patients who had received any dose of tislelizumab |
| Arm/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| Count of Participants [Participants] |
322
10733.3%
|
| Title | Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 145 |
| Non-Small Cell Lung Cancer |
63.9
(47.8)
|
| Ovarian Cancer |
90.4
(66.7)
|
| Gastric Cancer |
40.7
(91.4)
|
| Hepatocellular Carcinoma |
54.4
(56.8)
|
| Head & Neck Squamous Cell Carcinoma |
77.4
(45.8)
|
| Esophageal Carcinoma |
57.8
(62.4)
|
| Triple Negative Breast Cancer |
47.8
(78.9)
|
| Cholangio Carcinoma |
65.7
(47.9)
|
| Other Solid Tumors |
80.4
(43.5)
|
| Title | Phase 1B: PFS |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| Median (95% Confidence Interval) [months] |
2.1
|
| Title | Phase 1B: Disease Control Rate (DCR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| Number (95% Confidence Interval) [percentage of participants] |
41.2
1373.3%
|
| Title | Phase 1B: Clinical Benefit Rate (CBR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| Number (95% Confidence Interval) [percentage of participants] |
24.5
816.7%
|
| Title | Phase 1B: Number Of Participants With Abnormal Physical Examination Values |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who had received any dose of tislelizumab and with baseline. |
| Arm/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| At least one postbaseline pulse rate measure ≤ 45 bpm |
5
166.7%
|
| At least one postbaseline pulse rate measure ≥ 120 bpm |
26
866.7%
|
| At least one postbaseline SBP measure ≤ 60 mmHg |
1
33.3%
|
| At least one postbaseline SBP measure ≤ 90 mmHg |
24
800%
|
| At least one postbaseline SBP measure ≥ 160 mmHg |
30
1000%
|
| At least one postbaseline DBP measure ≥ 100 mmHg |
12
400%
|
| Title | Phase 1B: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAF) included all patients who had received any dose of tislelizumab. |
| Arm/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| Count of Participants [Participants] |
0
0%
|
| Title | Phase 1B: Number Of Participants With Abnormal Electrocardiograms |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who had received any dose of tislelizumab. |
| Arm/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| At least 1 postbaseline QTcF Interval measure > 450 msec |
84
2800%
|
| At least 1 postbaseline QTcF Interval measure > 480 msec |
24
800%
|
| At least 1 postbaseline QTcF Interval measure > 500 msec |
10
333.3%
|
| At least 1 postbaseline QTcF Interval measure ≤ 30 msec increase from baseline |
241
8033.3%
|
| At least 1 postbaseline QTcF Interval measure >30 and ≤ 60 msec increase from baseline |
67
2233.3%
|
| At least 1 postbaseline QTcF Interval measure > 60 msec increase |
22
733.3%
|
| Title | Phase 1B: Number Of Participants With Abnormal Laboratory Values |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: participants who had received any dose of tislelizumab. |
| Arm/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| Alanine Aminotransferase: High |
21
700%
|
| Albumin: Low |
42
1400%
|
| Alkaline Phosphatase: High |
21
700%
|
| Aspartate Aminotransferase: High |
21
700%
|
| Bilirubin: High |
22
733.3%
|
| Calcium: Low |
12
400%
|
| Calcium: High |
7
233.3%
|
| Creatinine: High |
20
666.7%
|
| Glucose: Low |
8
266.7%
|
| Glucose: High |
32
1066.7%
|
| Hemoglobin: Low |
19
633.3%
|
| Leukocytes: Low |
8
266.7%
|
| Leukocytes: High |
1
33.3%
|
| Lymphocytes: Low |
33
1100%
|
| Lymphocytes: High |
2
66.7%
|
| Neutrophils: Low |
5
166.7%
|
| Phosphate: Low |
42
1400%
|
| Platelets: Low |
3
100%
|
| Potassium: Low |
35
1166.7%
|
| Potassium: High |
4
133.3%
|
| Sodium: Low |
25
833.3%
|
| Sodium: High |
1
33.3%
|
| Title | Phase 1B: Number Of Participants Experiencing Severe AEs |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAF) included all patients who had received any dose of tislelizumab. |
| Arm/Group Title | BGB-A317 Phase 1B |
|---|---|
| Arm/Group Description | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. |
| Measure Participants | 335 |
| Count of Participants [Participants] |
27
900%
|
Adverse Events
| Time Frame | Day -28 through 5 years and 2 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | 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/Group Title | BGB-A317 Phase 1A | BGB-A317 Phase 1B | ||
| Arm/Group Description | In Part 1, participants were dosed at 0.5 mg/kg, 2 mg/kg, 5 mg/kg, and 10 mg/kg Q2W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days in duration. In Part 2, participants received selected dosing based on Part 1 at Q2W and/or Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent. Each treatment cycle was 28 days and 21 days in duration, respectively. In Part 3: participants received a fixed dose that did not exceed the selected MTD, which is 200 mg Q3W until death, disease progression, unacceptable toxicities, or withdrawal of consent.. Each treatment cycle was 21 days in duration. | Participants were dosed at 5 mg/kg Q3W until confirmed disease progression, intolerable toxicity, participant 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. | ||
All Cause Mortality |
||||
| BGB-A317 Phase 1A | BGB-A317 Phase 1B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 97/116 (83.6%) | 249/335 (74.3%) | ||
Serious Adverse Events |
||||
| BGB-A317 Phase 1A | BGB-A317 Phase 1B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 40/116 (34.5%) | 131/335 (39.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/116 (0.9%) | 1/335 (0.3%) | ||
| Lymphadenopathy | 0/116 (0%) | 2/335 (0.6%) | ||
| Iron deficiency anaemia | 0/116 (0%) | 1/335 (0.3%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 0/116 (0%) | 2/335 (0.6%) | ||
| Arteriosclerosis coronary artery | 0/116 (0%) | 1/335 (0.3%) | ||
| Myocardial ischaemia | 0/116 (0%) | 1/335 (0.3%) | ||
| Gastrointestinal disorders | ||||
| Vomiting | 2/116 (1.7%) | 6/335 (1.8%) | ||
| Abdominal pain | 3/116 (2.6%) | 3/335 (0.9%) | ||
| Ascites | 2/116 (1.7%) | 4/335 (1.2%) | ||
| Colitis | 3/116 (2.6%) | 2/335 (0.6%) | ||
| Dysphagia | 0/116 (0%) | 5/335 (1.5%) | ||
| Nausea | 2/116 (1.7%) | 3/335 (0.9%) | ||
| Diarrhoea | 2/116 (1.7%) | 2/335 (0.6%) | ||
| Upper gastrointestinal haemorrhage | 1/116 (0.9%) | 3/335 (0.9%) | ||
| Constipation | 0/116 (0%) | 3/335 (0.9%) | ||
| Small intestinal obstruction | 1/116 (0.9%) | 2/335 (0.6%) | ||
| Abdominal distension | 0/116 (0%) | 2/335 (0.6%) | ||
| Abdominal pain upper | 1/116 (0.9%) | 1/335 (0.3%) | ||
| Gastrointestinal haemorrhage | 0/116 (0%) | 2/335 (0.6%) | ||
| Intestinal obstruction | 0/116 (0%) | 2/335 (0.6%) | ||
| Oesophageal obstruction | 0/116 (0%) | 2/335 (0.6%) | ||
| Autoimmune colitis | 1/116 (0.9%) | 0/335 (0%) | ||
| Autoimmune pancreatitis | 1/116 (0.9%) | 0/335 (0%) | ||
| Duodenal ulcer | 1/116 (0.9%) | 0/335 (0%) | ||
| Dyspepsia | 0/116 (0%) | 1/335 (0.3%) | ||
| Faecaloma | 0/116 (0%) | 1/335 (0.3%) | ||
| Frequent bowel movements | 0/116 (0%) | 1/335 (0.3%) | ||
| Gastric ulcer | 0/116 (0%) | 1/335 (0.3%) | ||
| Gastric ulcer perforation | 0/116 (0%) | 1/335 (0.3%) | ||
| Gastric varices | 0/116 (0%) | 1/335 (0.3%) | ||
| Gastritis | 1/116 (0.9%) | 0/335 (0%) | ||
| Gastrointestinal obstruction | 0/116 (0%) | 1/335 (0.3%) | ||
| Gingival bleeding | 0/116 (0%) | 1/335 (0.3%) | ||
| Ileus | 0/116 (0%) | 1/335 (0.3%) | ||
| Lower gastrointestinal haemorrhage | 0/116 (0%) | 1/335 (0.3%) | ||
| Obstruction gastric | 0/116 (0%) | 1/335 (0.3%) | ||
| Oesophageal haemorrhage | 0/116 (0%) | 1/335 (0.3%) | ||
| Oesophageal varices haemorrhage | 0/116 (0%) | 1/335 (0.3%) | ||
| Small intestinal haemorrhage | 0/116 (0%) | 1/335 (0.3%) | ||
| Stomatitis | 0/116 (0%) | 1/335 (0.3%) | ||
| General disorders | ||||
| Pyrexia | 2/116 (1.7%) | 6/335 (1.8%) | ||
| Asthenia | 0/116 (0%) | 1/335 (0.3%) | ||
| Fatigue | 0/116 (0%) | 1/335 (0.3%) | ||
| Multiple organ dysfunction syndrome | 1/116 (0.9%) | 0/335 (0%) | ||
| Oedema peripheral | 1/116 (0.9%) | 0/335 (0%) | ||
| Peripheral swelling | 1/116 (0.9%) | 0/335 (0%) | ||
| Hepatobiliary disorders | ||||
| Hepatitis | 0/116 (0%) | 3/335 (0.9%) | ||
| Cholangitis | 0/116 (0%) | 2/335 (0.6%) | ||
| Bile duct obstruction | 0/116 (0%) | 1/335 (0.3%) | ||
| Cholangitis acute | 0/116 (0%) | 1/335 (0.3%) | ||
| Hepatic failure | 0/116 (0%) | 1/335 (0.3%) | ||
| Hepatitis acute | 0/116 (0%) | 1/335 (0.3%) | ||
| Jaundice cholestatic | 0/116 (0%) | 1/335 (0.3%) | ||
| Immune system disorders | ||||
| Contrast media allergy | 0/116 (0%) | 1/335 (0.3%) | ||
| Infections and infestations | ||||
| Pneumonia | 4/116 (3.4%) | 16/335 (4.8%) | ||
| Lower respiratory tract infection | 0/116 (0%) | 4/335 (1.2%) | ||
| Sepsis | 0/116 (0%) | 4/335 (1.2%) | ||
| Infective exacerbation of chronic obstructive airways disease | 0/116 (0%) | 2/335 (0.6%) | ||
| Septic shock | 0/116 (0%) | 2/335 (0.6%) | ||
| Acute sinusitis | 1/116 (0.9%) | 0/335 (0%) | ||
| Bacterascites | 0/116 (0%) | 1/335 (0.3%) | ||
| Biliary tract infection | 0/116 (0%) | 1/335 (0.3%) | ||
| Bone tuberculosis | 0/116 (0%) | 1/335 (0.3%) | ||
| Breast cellulitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Bronchitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Campylobacter gastroenteritis | 1/116 (0.9%) | 0/335 (0%) | ||
| Cellulitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Complicated appendicitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Diverticulitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Gastroenteritis salmonella | 0/116 (0%) | 1/335 (0.3%) | ||
| Infection | 0/116 (0%) | 1/335 (0.3%) | ||
| Mediastinitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Orbital infection | 0/116 (0%) | 1/335 (0.3%) | ||
| Osteomyelitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Parotitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Peritonitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Pneumonia bacterial | 0/116 (0%) | 1/335 (0.3%) | ||
| Respiratory syncytial virus infection | 0/116 (0%) | 1/335 (0.3%) | ||
| Sinusitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Soft tissue infection | 0/116 (0%) | 1/335 (0.3%) | ||
| Tooth infection | 1/116 (0.9%) | 0/335 (0%) | ||
| Upper respiratory tract infection | 0/116 (0%) | 1/335 (0.3%) | ||
| Urinary tract infection | 0/116 (0%) | 1/335 (0.3%) | ||
| Vascular device infection | 1/116 (0.9%) | 0/335 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 1/116 (0.9%) | 1/335 (0.3%) | ||
| Procedural pain | 0/116 (0%) | 2/335 (0.6%) | ||
| Fall | 0/116 (0%) | 1/335 (0.3%) | ||
| Hand fracture | 1/116 (0.9%) | 0/335 (0%) | ||
| Procedural hypotension | 0/116 (0%) | 1/335 (0.3%) | ||
| Toxicity to various agents | 0/116 (0%) | 1/335 (0.3%) | ||
| Investigations | ||||
| Aspartate aminotransferase increased | 0/116 (0%) | 2/335 (0.6%) | ||
| Alanine aminotransferase increased | 0/116 (0%) | 1/335 (0.3%) | ||
| Blood creatinine increased | 1/116 (0.9%) | 0/335 (0%) | ||
| Ejection fraction decreased | 1/116 (0.9%) | 0/335 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Cachexia | 0/116 (0%) | 2/335 (0.6%) | ||
| Diabetic ketoacidosis | 2/116 (1.7%) | 0/335 (0%) | ||
| Hyperglycaemia | 2/116 (1.7%) | 0/335 (0%) | ||
| Hypokalaemia | 1/116 (0.9%) | 1/335 (0.3%) | ||
| Type 1 diabetes mellitus | 2/116 (1.7%) | 0/335 (0%) | ||
| Decreased appetite | 0/116 (0%) | 1/335 (0.3%) | ||
| Dehydration | 1/116 (0.9%) | 0/335 (0%) | ||
| Hyperkalaemia | 0/116 (0%) | 1/335 (0.3%) | ||
| Hypomagnesaemia | 1/116 (0.9%) | 0/335 (0%) | ||
| Latent autoimmune diabetes in adults | 1/116 (0.9%) | 0/335 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/116 (1.7%) | 4/335 (1.2%) | ||
| Arthralgia | 0/116 (0%) | 1/335 (0.3%) | ||
| Arthritis | 0/116 (0%) | 1/335 (0.3%) | ||
| Musculoskeletal chest pain | 1/116 (0.9%) | 0/335 (0%) | ||
| Pathological fracture | 0/116 (0%) | 1/335 (0.3%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant ascites | 0/116 (0%) | 2/335 (0.6%) | ||
| Squamous cell carcinoma of skin | 1/116 (0.9%) | 1/335 (0.3%) | ||
| Adenocarcinoma of colon | 0/116 (0%) | 1/335 (0.3%) | ||
| Basal cell carcinoma | 1/116 (0.9%) | 0/335 (0%) | ||
| Lip squamous cell carcinoma | 0/116 (0%) | 1/335 (0.3%) | ||
| Malignant neoplasm progression | 0/116 (0%) | 1/335 (0.3%) | ||
| Tumour haemorrhage | 0/116 (0%) | 1/335 (0.3%) | ||
| Nervous system disorders | ||||
| Basal ganglia infarction | 1/116 (0.9%) | 0/335 (0%) | ||
| Brain oedema | 0/116 (0%) | 1/335 (0.3%) | ||
| Dysaesthesia | 0/116 (0%) | 1/335 (0.3%) | ||
| Headache | 0/116 (0%) | 1/335 (0.3%) | ||
| IIIrd nerve paralysis | 0/116 (0%) | 1/335 (0.3%) | ||
| Lethargy | 0/116 (0%) | 1/335 (0.3%) | ||
| Sciatica | 0/116 (0%) | 1/335 (0.3%) | ||
| Spinal cord compression | 0/116 (0%) | 1/335 (0.3%) | ||
| Thoracic radiculopathy | 1/116 (0.9%) | 0/335 (0%) | ||
| Product Issues | ||||
| Device occlusion | 0/116 (0%) | 1/335 (0.3%) | ||
| Psychiatric disorders | ||||
| Delirium | 0/116 (0%) | 1/335 (0.3%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/116 (0%) | 1/335 (0.3%) | ||
| Haematuria | 0/116 (0%) | 1/335 (0.3%) | ||
| Urinary retention | 0/116 (0%) | 1/335 (0.3%) | ||
| Urinary tract obstruction | 1/116 (0.9%) | 0/335 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonitis | 1/116 (0.9%) | 8/335 (2.4%) | ||
| Pleural effusion | 1/116 (0.9%) | 5/335 (1.5%) | ||
| Pulmonary embolism | 3/116 (2.6%) | 1/335 (0.3%) | ||
| Dyspnoea | 1/116 (0.9%) | 0/335 (0%) | ||
| Epistaxis | 0/116 (0%) | 1/335 (0.3%) | ||
| Haemoptysis | 0/116 (0%) | 1/335 (0.3%) | ||
| Immune-mediated pneumonitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Pleuritic pain | 0/116 (0%) | 1/335 (0.3%) | ||
| Pneumonia aspiration | 0/116 (0%) | 1/335 (0.3%) | ||
| Pneumothorax | 1/116 (0.9%) | 0/335 (0%) | ||
| Respiratory failure | 0/116 (0%) | 1/335 (0.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis | 0/116 (0%) | 1/335 (0.3%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 0/116 (0%) | 1/335 (0.3%) | ||
| Haematoma | 1/116 (0.9%) | 0/335 (0%) | ||
| Hypotension | 1/116 (0.9%) | 0/335 (0%) | ||
| Jugular vein thrombosis | 0/116 (0%) | 1/335 (0.3%) | ||
| Lymphoedema | 0/116 (0%) | 1/335 (0.3%) | ||
| Venous occlusion | 1/116 (0.9%) | 0/335 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| BGB-A317 Phase 1A | BGB-A317 Phase 1B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 112/116 (96.6%) | 302/335 (90.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 12/116 (10.3%) | 28/335 (8.4%) | ||
| Endocrine disorders | ||||
| Hypothyroidism | 8/116 (6.9%) | 22/335 (6.6%) | ||
| Hyperthyroidism | 5/116 (4.3%) | 14/335 (4.2%) | ||
| Eye disorders | ||||
| Dry eye | 7/116 (6%) | 7/335 (2.1%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 41/116 (35.3%) | 71/335 (21.2%) | ||
| Diarrhoea | 33/116 (28.4%) | 49/335 (14.6%) | ||
| Constipation | 28/116 (24.1%) | 51/335 (15.2%) | ||
| Abdominal pain | 25/116 (21.6%) | 42/335 (12.5%) | ||
| Vomiting | 19/116 (16.4%) | 42/335 (12.5%) | ||
| Abdominal pain upper | 9/116 (7.8%) | 19/335 (5.7%) | ||
| Abdominal distension | 6/116 (5.2%) | 17/335 (5.1%) | ||
| Gastrooesophageal reflux disease | 6/116 (5.2%) | 17/335 (5.1%) | ||
| Dry mouth | 6/116 (5.2%) | 11/335 (3.3%) | ||
| Dysphagia | 3/116 (2.6%) | 11/335 (3.3%) | ||
| Ascites | 5/116 (4.3%) | 4/335 (1.2%) | ||
| Dyspepsia | 4/116 (3.4%) | 4/335 (1.2%) | ||
| Mouth ulceration | 4/116 (3.4%) | 3/335 (0.9%) | ||
| General disorders | ||||
| Fatigue | 47/116 (40.5%) | 80/335 (23.9%) | ||
| Pyrexia | 7/116 (6%) | 31/335 (9.3%) | ||
| Oedema peripheral | 13/116 (11.2%) | 24/335 (7.2%) | ||
| Non-cardiac chest pain | 9/116 (7.8%) | 12/335 (3.6%) | ||
| Influenza like illness | 4/116 (3.4%) | 6/335 (1.8%) | ||
| Infections and infestations | ||||
| Upper respiratory tract infection | 15/116 (12.9%) | 28/335 (8.4%) | ||
| Urinary tract infection | 8/116 (6.9%) | 22/335 (6.6%) | ||
| Oral candidiasis | 8/116 (6.9%) | 17/335 (5.1%) | ||
| Lower respiratory tract infection | 4/116 (3.4%) | 11/335 (3.3%) | ||
| Pneumonia | 4/116 (3.4%) | 9/335 (2.7%) | ||
| Nasopharyngitis | 4/116 (3.4%) | 7/335 (2.1%) | ||
| Oral herpes | 4/116 (3.4%) | 2/335 (0.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 12/116 (10.3%) | 13/335 (3.9%) | ||
| Investigations | ||||
| Weight decreased | 5/116 (4.3%) | 35/335 (10.4%) | ||
| Alanine aminotransferase increased | 9/116 (7.8%) | 17/335 (5.1%) | ||
| Aspartate aminotransferase increased | 4/116 (3.4%) | 18/335 (5.4%) | ||
| Blood creatinine increased | 7/116 (6%) | 12/335 (3.6%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 20/116 (17.2%) | 74/335 (22.1%) | ||
| Hypokalaemia | 5/116 (4.3%) | 17/335 (5.1%) | ||
| Hypercalcaemia | 6/116 (5.2%) | 15/335 (4.5%) | ||
| Hypomagnesaemia | 5/116 (4.3%) | 8/335 (2.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 26/116 (22.4%) | 40/335 (11.9%) | ||
| Arthralgia | 10/116 (8.6%) | 23/335 (6.9%) | ||
| Musculoskeletal pain | 8/116 (6.9%) | 21/335 (6.3%) | ||
| Musculoskeletal chest pain | 11/116 (9.5%) | 11/335 (3.3%) | ||
| Pain in extremity | 10/116 (8.6%) | 12/335 (3.6%) | ||
| Muscle spasms | 7/116 (6%) | 7/335 (2.1%) | ||
| Myalgia | 7/116 (6%) | 7/335 (2.1%) | ||
| Nervous system disorders | ||||
| Headache | 9/116 (7.8%) | 28/335 (8.4%) | ||
| Dizziness | 10/116 (8.6%) | 12/335 (3.6%) | ||
| Lethargy | 5/116 (4.3%) | 2/335 (0.6%) | ||
| Psychiatric disorders | ||||
| Insomnia | 5/116 (4.3%) | 29/335 (8.7%) | ||
| Anxiety | 8/116 (6.9%) | 6/335 (1.8%) | ||
| Renal and urinary disorders | ||||
| Proteinuria | 3/116 (2.6%) | 14/335 (4.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 17/116 (14.7%) | 46/335 (13.7%) | ||
| Dyspnoea | 11/116 (9.5%) | 35/335 (10.4%) | ||
| Oropharyngeal pain | 2/116 (1.7%) | 12/335 (3.6%) | ||
| Productive cough | 5/116 (4.3%) | 9/335 (2.7%) | ||
| Dyspnoea exertional | 6/116 (5.2%) | 7/335 (2.1%) | ||
| Wheezing | 4/116 (3.4%) | 8/335 (2.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 23/116 (19.8%) | 39/335 (11.6%) | ||
| Pruritus | 21/116 (18.1%) | 38/335 (11.3%) | ||
| Rash maculo-papular | 9/116 (7.8%) | 12/335 (3.6%) | ||
| Dry skin | 2/116 (1.7%) | 12/335 (3.6%) | ||
| Rash erythematous | 4/116 (3.4%) | 6/335 (1.8%) | ||
| Night sweats | 7/116 (6%) | 1/335 (0.3%) | ||
| Hyperhidrosis | 4/116 (3.4%) | 2/335 (0.6%) | ||
| Vascular disorders | ||||
| Hot flush | 4/116 (3.4%) | 6/335 (1.8%) | ||
| Hypotension | 5/116 (4.3%) | 5/335 (1.5%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | BeiGene |
| Phone | +1-877-828-5568 |
| clinicaltrials@beigene.com |
Responsible Party:
BeiGene
ClinicalTrials.gov Identifier:
NCT02407990
Other Study ID Numbers:
- BGB-A317_Study_001
First Posted:
Apr 3, 2015
Last Update Posted:
Nov 17, 2021
Last Verified:
Oct 1, 2021