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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02407990




Registration number
NCT02407990
Ethics application status
Date submitted
26/03/2015
Date registered
3/04/2015

Titles & IDs
Public title
Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors
Scientific 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
Secondary ID [1] 0 0
BGB-A317_Study_001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - BGB-A317
Treatment: Other - BGB-A317

Experimental: BGB-A317 Phase 1A -

Experimental: BGB-A317 Phase 1B -


Treatment: Other: 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.

Treatment: Other: BGB-A317
Participants were assigned to different groups based on their tumor types

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1A: Number of Participants Experiencing Adverse Events (AEs)
Timepoint [1] 0 0
Day -28 through 5 years and 2 months
Primary outcome [2] 0 0
Phase 1A: Number Of Participants With Abnormal Physical Examination Values
Timepoint [2] 0 0
Day 1 and Day 15 of each cycle through 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Primary outcome [3] 0 0
Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings
Timepoint [3] 0 0
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)
Primary outcome [4] 0 0
Phase 1A: Number Of Participants With Abnormal Electrocardiograms
Timepoint [4] 0 0
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)
Primary outcome [5] 0 0
Phase 1A: Number Of Participants With Abnormal Laboratory Values
Timepoint [5] 0 0
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)
Primary outcome [6] 0 0
Phase 1A: Number Of Participants Experiencing Severe AEs
Timepoint [6] 0 0
Day -28 through 5 years and 2 months
Primary outcome [7] 0 0
Phase 1B: Objective Response Rate (ORR)
Timepoint [7] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [1] 0 0
Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Phase 1A: Half-life (T½) For Tislelizumab
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Phase 1A - Part 3: Clearance (Cl) For Tislelizumab
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs)
Timepoint [6] 0 0
Day 1 of Cycles 1 through 15
Secondary outcome [7] 0 0
Phase 1A: ORR
Timepoint [7] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [8] 0 0
Phase 1A: CR Rate
Timepoint [8] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [9] 0 0
Phase 1A: PR Rate
Timepoint [9] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [10] 0 0
Phase 1A: Stable Disease (SD) Rate
Timepoint [10] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [11] 0 0
Phase 1A: Progression-free Survival (PFS)
Timepoint [11] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [12] 0 0
Phase 1A: Overall Survival (OS)
Timepoint [12] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [13] 0 0
Phase 1A: Duration Of Response (DOR)
Timepoint [13] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [14] 0 0
Phase 1B: Number of Participants Experiencing AEs
Timepoint [14] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [15] 0 0
Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab
Timepoint [15] 0 0
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)
Secondary outcome [16] 0 0
Phase 1B: PFS
Timepoint [16] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [17] 0 0
Phase 1B: Disease Control Rate (DCR)
Timepoint [17] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [18] 0 0
Phase 1B: Clinical Benefit Rate (CBR)
Timepoint [18] 0 0
Day -28 through 5 years and 2 months
Secondary outcome [19] 0 0
Phase 1B: Number Of Participants With Abnormal Physical Examination Values
Timepoint [19] 0 0
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
Secondary outcome [20] 0 0
Phase 1B: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings
Timepoint [20] 0 0
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
Secondary outcome [21] 0 0
Phase 1B: Number Of Participants With Abnormal Electrocardiograms
Timepoint [21] 0 0
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
Secondary outcome [22] 0 0
Phase 1B: Number Of Participants With Abnormal Laboratory Values
Timepoint [22] 0 0
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
Secondary outcome [23] 0 0
Phase 1B: Number Of Participants Experiencing Severe AEs
Timepoint [23] 0 0
Day -28 through 5 years and 2 months

Eligibility
Key inclusion criteria
Key

1. Participants must have had a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy was available.

1. For Phase 1A: no specific restriction
2. For Phase 1B: histology specified below:

i. non-small cell lung cancer (participants with documented epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement should have been excluded) ii. ovarian cancer iii. gastric cancer iv. hepatocellular carcinoma (HCC, Barcelona-Clinic Liver Cancer stage C, stage B not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach, and Child-Pugh A) v. head and neck squamous cell carcinoma vi. esophageal carcinoma vii. triple negative breast cancer viii. cholangiocarcinoma ix. renal cell cancer, bladder cancer, melanoma, Merkel-cell carcinoma, sarcoma, gastrointestinal stromal tumor, or cutaneous squamous cell carcinoma. Or any other solid tumors with known microsatellite instability-high or mismatch repair deficient status, such as colorectal cancer or pancreatic cancer
2. Participants with previously treated brain metastasis (es) that were asymptomatic or radiographically/clinically stable and not requiring steroids medications for 4 weeks prior to enrollment were permitted.
3. Participants must have had archival tumor tissues or agreed to a tumor biopsy for analysis of predictive biomarkers such as programmed death-ligand 1 (PD-L1). (Fresh tumor biopsies were strongly recommended at baseline for biomarker analysis in participants with readily accessible tumor lesions and who consented to the biopsies).
4. Participants must have had measurable disease as defined per Response Evaluation Criteria in Solid Tumor Version 1.1.
5. Eastern Cooperative Oncology Group performance status of = 1.
6. Participants must have had adequate organ function as indicated by the following laboratory values:

* Absolute neutrophil count = 1,500 /microliter
* Platelets = 100,000 / milliliter (mL)
* Hemoglobin = 9 grams/deciliter or = 5.6 millimoles/liter
* Serum creatinine = 1.5 X upper limit of normal (ULN)
* Serum total bilirubin = 1.5 X ULN
* Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) = 2.5 X ULN or = 5 X ULN for participants with liver metastases
* International normalized ratio or prothrombin time = 1.5 X ULN
* Activated partial thromboplastin time = 1.5 X ULN

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of severe hypersensitivity reactions to other Monoclonal antibodies.
2. Prior malignancy active within the previous 2 years except for tumor for which a participant was enrolled in the study, and locally curable cancers that had been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
3. Prior therapies targeting PD-1 or PD-L1.
4. Participants who failed to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers.
5. Participants with active autoimmune diseases or history of autoimmune diseases should have been excluded.
6. Participants should have been excluded if they had a condition requiring systemic treatment with either corticosteroids (> 10 milligrams daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
7. Had history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
8. Known history of human immunodeficiency virus.
9. Active infection requiring therapy, positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid except in participant with HCC, who met the following criteria:

* Hepatitis B virus (HBV) viral load < 200 international units/mL (approximately 1000 combined positive score/mL)
* Participants with active HBV infection needed to be on anti-HBV suppression = 3 months, throughout treatment and for 6 months after
* Participants hepatitis C virus (HCV)-positive after successful treatment (defined as sustained virologic response [SVR] 12 or SVR 24) were allowed as long as 4 weeks had passed between completion of HCV therapy and start of study drug
10. Use of any vaccines against infectious diseases (for example, influenza, varicella) within 4 weeks (28 days) of initiation of study therapy and 60 days after the last administration of the study medication.

Note: Other protocol defined Inclusion/Exclusion criteria may have applied.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [3] 0 0
Tasman Oncology Research Ltd - Southport
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [7] 0 0
Monash Health - Clayton
Recruitment hospital [8] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [9] 0 0
Austin Health Hospital - Heidelberg
Recruitment hospital [10] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [11] 0 0
Nucleus Network - Melbourne
Recruitment hospital [12] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [13] 0 0
Linear Clinical Research/Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
4216 - Southport
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
- Adelaide
Recruitment postcode(s) [6] 0 0
- Woodville South
Recruitment postcode(s) [7] 0 0
- Clayton
Recruitment postcode(s) [8] 0 0
- East Melbourne
Recruitment postcode(s) [9] 0 0
- Heidelberg
Recruitment postcode(s) [10] 0 0
3144 - Malvern
Recruitment postcode(s) [11] 0 0
3004 - Melbourne
Recruitment postcode(s) [12] 0 0
- Melbourne
Recruitment postcode(s) [13] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
Korea, Republic of
State/province [3] 0 0
Kyeonggi-do
Country [4] 0 0
Korea, Republic of
State/province [4] 0 0
Seoul
Country [5] 0 0
New Zealand
State/province [5] 0 0
Grafton
Country [6] 0 0
New Zealand
State/province [6] 0 0
Hamilton
Country [7] 0 0
New Zealand
State/province [7] 0 0
Wellington
Country [8] 0 0
Taiwan
State/province [8] 0 0
Kaohsiung
Country [9] 0 0
Taiwan
State/province [9] 0 0
Tainan
Country [10] 0 0
Taiwan
State/province [10] 0 0
Taipei
Country [11] 0 0
Taiwan
State/province [11] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?


Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Desai J, Deva S, Lee JS, Lin CC, Yen CJ, Chao Y, K... [More Details]