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

NCT ID: NCT02407990

Last Updated: 2021-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 451 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-02
• Study Completion Date: 2020-08-12

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BGB-A317 Phase 1A

Group Type: EXPERIMENTAL

BGB-A317

Intervention Type: 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 1B

Group Type: EXPERIMENTAL

BGB-A317

Intervention Type: BIOLOGICAL

Participants were assigned to different groups based on their tumor types

Interventions

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.

Intervention Type: BIOLOGICAL

BGB-A317

Participants were assigned to different groups based on their tumor types

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: PRINCIPAL_INVESTIGATOR

BeiGene

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Oncology Consultants, P.A.

Houston, Texas, United States

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Prince of Wales Hospital

Sydney, New South Wales, Australia

Tasman Oncology Research Ltd

Southport, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Monash Health

Clayton, Victoria, Australia

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Austin Health Hospital

Heidelberg, Victoria, Australia

Cabrini Hospital

Malvern, Victoria, Australia

Nucleus Network

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Linear Clinical Research/Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Auckland City Hospital

Grafton, , New Zealand

Waikato

Hamilton, , New Zealand

Wellington Hospital

Wellington, , New Zealand

Seoul National University Bundang Hospital

Seongnam, Kyeonggi-do, South Korea

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Linkou Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Chang Gung Memorial Hospital, Sachin

Taoyuan District, , Taiwan

Countries

United States; Australia; New Zealand; South Korea; Taiwan

References

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.

Reference Type: RESULT

PMID: 32540858 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36879284 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BGB-A317_Study_001

Identifier Type: -

Identifier Source: org_study_id