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

NCT02407990 | Completed Phase 1 Results FDA Drug

• 1 other identifier: BGB-A317_Study_001
• Study Type: interventional
• Target: 451
• Locations: 5 countries
• Sites: 27

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.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (7)

• Phase 1A: Number of Participants Experiencing Adverse Events (AEs)

  An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product. All AEs were monitored per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version \[v\] 4.03 2010).

  Day -28 through 5 years and 2 months

• Phase 1A: Number Of Participants With Abnormal Physical Examination Values

  A complete physical examination, vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, temperature, and respiratory rate), and weight were performed pre-specified time points for Phase 1A. During the treatment period, symptom-directed physical examinations were performed. If there were no complaints and no abnormal findings from the previous visit for a particular organ system, a physical examination of that organ system was not required.

  Day 1 and Day 15 of each cycle through 30 (+/- 7) days after last dose (up to 5 years and 2 months)

• Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings

  Ophthalmological examinations (such as eyesight/visual acuity, fundoscopy, slit lamp microscopy, and optical coherence tomography \[or equivalent diagnostic test\]) were performed at pre-specified time points for Phase 1A. Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) will be assessed by an appropriate specialist at Screening. Participants dosed underwent subsequent ophthalmologic examinations, a specified in the protocol, by an appropriate specialist during study treatment.

  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)

• Phase 1A: Number Of Participants With Abnormal Electrocardiograms

  Electrocardiograms were obtained at pre-specified time points. Significant QT interval corrected for heart rate (QTc) prolongation was defined as an interval ≥ 500 milliseconds (msec) or an interval which increases by ≥ 60 msec over baseline.

  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)

• Phase 1A: Number Of Participants With Abnormal Laboratory Values

  Clinical chemistry, hematology, coagulation, and urinalysis were performed at pre-specified time points for Phase 1A. If warranted, additional testing was done, or the relevant tests done more frequently in accordance with institutional guidelines. All participants who had any Grade 3 or Grade 4 laboratory abnormalities at withdrawal from the study were followed up until they had returned to Grade 1 or Grade 2, unless these were not likely to improve due to the underlying disease. Participants experiencing decreases (low) and increases (high) to ≥ Grade 3 are reported.

  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)

• Phase 1A: Number Of Participants Experiencing Severe AEs

  All AEs were monitored per the NCI-CTCAE (v 4.03 2010). In addition to performing the CTCAE assessment, the intensity of each AE and serious adverse event (SAE) recorded was assigned to one of the following categories based on the Investigator's clinical judgment: Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate: An event that is sufficiently discomforting to interfere with normal everyday activities; severe: An event that prevents normal everyday activities. Severity was a category utilized for rating the intensity of an event and, accordingly, both AEs and SAEs could be assessed as severe.

  Day -28 through 5 years and 2 months

• Phase 1B: Objective Response Rate (ORR)

  The ORR was defined as the percentage of participants in the study whose best overall response was either complete response (CR) or partial response (PR) as assessed by investigators based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.

  Day -28 through 5 years and 2 months

Secondary Outcomes (23)

• 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

Study Arms (2)

BGB-A317 Phase 1A

EXPERIMENTAL

Biological: BGB-A317

BGB-A317 Phase 1B

EXPERIMENTAL

Biological: BGB-A317

Interventions

BGB-A317 BIOLOGICAL

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.

BGB-A317 Phase 1A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (27)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Oncology Consultants, P.A.

Houston, Texas, 77024-2545, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Prince of Wales Hospital

Sydney, New South Wales, Australia

Location

Tasman Oncology Research Ltd

Southport, Queensland, 4216, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Location

Monash Health

Clayton, Victoria, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Location

Austin Health Hospital

Heidelberg, Victoria, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Location

Linear Clinical Research/Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Location

Auckland City Hospital

Grafton, 1023, New Zealand

Location

Waikato

Hamilton, 3204, New Zealand

Location

Wellington Hospital

Wellington, 6022, New Zealand

Location

Seoul National University Bundang Hospital

Seongnam, Kyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan District, 33305, Taiwan

Location

Chang Gung Memorial Hospital, Sachin

Taoyuan District, 61363, Taiwan

Location

Related Publications (2)

• 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):e000453. doi: 10.1136/jitc-2019-000453.

  PMID: 32540858 RESULT

• Ye D, Desai J, Shi J, Liu SM, Shen W, Liu T, Shi Y, Wang D, Liang L, Yang S, Ma X, Jin W, Zhang P, Huang R, Shen Z, Zhang Y, Wu YL. Co-enrichment of CD8-positive T cells and macrophages is associated with clinical benefit of tislelizumab in solid tumors. Biomark Res. 2023 Mar 7;11(1):25. doi: 10.1186/s40364-023-00465-w.

  PMID: 36879284 DERIVED

MeSH Terms

Interventions

tislelizumab

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2015
• First Posted: April 3, 2015
• Study Start: June 2, 2015
• Primary Completion: August 12, 2020
• Study Completion: August 12, 2020
• Last Updated: November 17, 2021
• Results First Posted: November 17, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

NZ (3); US (2); KR (3); AU (13); TW (6)