We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02407990
Recruitment Status : Completed
First Posted : April 3, 2015
Results First Posted : November 17, 2021
Last Update Posted : November 17, 2021
Sponsor:
Information provided by (Responsible Party):
BeiGene

Tracking Information
First Submitted Date  ICMJE March 26, 2015
First Posted Date  ICMJE April 3, 2015
Results First Submitted Date  ICMJE August 6, 2021
Results First Posted Date  ICMJE November 17, 2021
Last Update Posted Date November 17, 2021
Actual Study Start Date  ICMJE June 2, 2015
Actual Primary Completion Date August 12, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2021)
  • Phase 1A: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: 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 [ Time Frame: 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 [ 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) ]
    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 [ 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) ]
    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 [ 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) ]
    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 [ Time Frame: 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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 31, 2015)
Number of participants with adverse events [ Time Frame: From first dose to within 30 days of last dose of BGB-A317, up to 2 years and 1 month ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2021)
  • Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab [ Time Frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose ]
  • Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab [ Time Frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose ]
  • Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab [ Time Frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose ]
  • Phase 1A: Half-life (T½) For Tislelizumab [ Time Frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose ]
  • Phase 1A - Part 3: Clearance (Cl) For Tislelizumab [ Time Frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose ]
  • Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ 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) ]
  • Phase 1B: PFS [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2015)
  • Area under the plasma concentration-time curve (AUC) [ Time Frame: During first 4 months ]
  • Maximum plasma concentration (Cmax) [ Time Frame: During first 4 months ]
  • Time to reach maximum plasma concentration (Tmax) [ Time Frame: During first 4 months ]
  • Terminal elimination half-life (t1/2) [ Time Frame: During first 4 months ]
  • Disease assessment by CT/MRI scan [ Time Frame: Performed at an expected average of 10 weeks during treatment period (up to 2 years) and within 30 days of last dose of BGB-A317 during follow-up period ]
  • Anti-BGB-A317 antibody [ Time Frame: Performed at an expected average of 6 weeks during treatment period (up to 2 years) and within 30 days of last dose of BGB-A317 during follow-up period ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Cancer
Intervention  ICMJE
  • 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.
  • Biological: BGB-A317
    Participants were assigned to different groups based on their tumor types
Study Arms  ICMJE
  • Experimental: BGB-A317 Phase 1A
    Intervention: Biological: BGB-A317
  • Experimental: BGB-A317 Phase 1B
    Intervention: Biological: BGB-A317
Publications * Desai J, Deva S, Lee JS, Lin CC, Yen CJ, Chao Y, Keam B, Jameson M, Hou MM, Kang YK, Markman B, Lu CH, Rau KM, Lee KH, Horvath L, Friedlander M, Hill A, Sandhu S, Barlow P, Wu CY, Zhang Y, Liang L, Wu J, Paton V, Millward M. Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. J Immunother Cancer. 2020 Jun;8(1). pii: e000453. doi: 10.1136/jitc-2019-000453.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 12, 2017)
451
Original Estimated Enrollment  ICMJE
 (submitted: March 31, 2015)
64
Actual Study Completion Date  ICMJE August 12, 2020
Actual Primary Completion Date August 12, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

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

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

    i. non-small cell lung cancer (participants with documented epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement should have been excluded) ii. ovarian cancer iii. gastric cancer iv. hepatocellular carcinoma (HCC, Barcelona-Clinic Liver Cancer stage C, stage B not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach, and Child-Pugh A) v. head and neck squamous cell carcinoma vi. esophageal carcinoma vii. triple negative breast cancer viii. cholangiocarcinoma ix. renal cell cancer, bladder cancer, melanoma, Merkel-cell carcinoma, sarcoma, gastrointestinal stromal tumor, or cutaneous squamous cell carcinoma. Or any other solid tumors with known microsatellite instability-high or mismatch repair deficient status, such as colorectal cancer or pancreatic cancer

  2. Participants with previously treated brain metastasis (es) that were asymptomatic or radiographically/clinically stable and not requiring steroids medications for 4 weeks prior to enrollment were permitted.
  3. Participants must have had archival tumor tissues or agreed to a tumor biopsy for analysis of predictive biomarkers such as programmed death-ligand 1 (PD-L1). (Fresh tumor biopsies were strongly recommended at baseline for biomarker analysis in participants with readily accessible tumor lesions and who consented to the biopsies).
  4. Participants must have had measurable disease as defined per Response Evaluation Criteria in Solid Tumor Version 1.1.
  5. Eastern Cooperative Oncology Group performance status of ≤ 1.
  6. Participants must have had adequate organ function as indicated by the following laboratory values:

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

Key Exclusion Criteria:

  1. History of severe hypersensitivity reactions to other Monoclonal antibodies.
  2. Prior malignancy active within the previous 2 years except for tumor for which a participant was enrolled in the study, and locally curable cancers that had been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
  3. Prior therapies targeting PD-1 or PD-L1.
  4. Participants who failed to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers.
  5. Participants with active autoimmune diseases or history of autoimmune diseases should have been excluded.
  6. Participants should have been excluded if they had a condition requiring systemic treatment with either corticosteroids (> 10 milligrams daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
  7. Had history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
  8. Known history of human immunodeficiency virus.
  9. Active infection requiring therapy, positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid except in participant with HCC, who met the following criteria:

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

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Korea, Republic of,   New Zealand,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02407990
Other Study ID Numbers  ICMJE BGB-A317_Study_001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Current Responsible Party BeiGene
Original Responsible Party Same as current
Current Study Sponsor  ICMJE BeiGene
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Study Director BeiGene
PRS Account BeiGene
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP