BGB A317 in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Esophageal, Gastric, or Gastroesophageal Junction Carcinoma
A Phase 2, Multi-Cohort Study to Investigate the Safety, Pharmacokinetics and Preliminary Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB A317 in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Esophageal, Gastric, or Gastroesophageal Junction Carcinoma
2 other identifiers
interventional
30
1 country
6
Brief Summary
This is a Phase 2, multi-cohort study to investigate safety, PK, and preliminary anti-tumor activity of the monoclonal antibody BGB A317 in combination with standard chemotherapy as first-line treatment. Cohorts include an ESCC cohort and a gastric carcinoma (GC) or GEJ carcinoma cohort that will be enrolled concurrently. The study includes a screening (up to 28 days), treatment (until disease progression, intolerable toxicity, or treatment withdrawal for another reason), safety follow-up (up to 30 days following last study drug treatment), and survival follow-up phase.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2017
Typical duration for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 18, 2017
CompletedFirst Submitted
Initial submission to the registry
February 8, 2018
CompletedFirst Posted
Study publicly available on registry
March 19, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
August 19, 2020
CompletedOctober 23, 2024
October 1, 2024
1.7 years
February 8, 2018
October 21, 2024
Conditions
Outcome Measures
Primary Outcomes (6)
The objective response rate (ORR) as assessed by RECIST, Version 1.1
Through study completion, an average of 9 months
The Duration of Response (DoR) as assessed by RECIST, Version 1.1
Through study completion, an average of 9 months
The Disease Control Rate (DCR) as assessed by RECIST, Version 1.1
Through study completion, an average of 9 months
The Progression-Free Survival (PFS) as assessed by RECIST, Version 1.1
Through study completion, an average of 9 months
Pharmacokinetic evaluations: include but not limited to minimum observed serum concentration (Ctrough) for BGB-A317.
Through study completion, an average of 10 months
Host immunogenicity: BGB-A317 anti-drug antibody (ADA)
Through study completion, an average of 10 months
Study Arms (2)
Esophageal Squamous Cell Carcinoma (ESCC)
EXPERIMENTALGastric (GC) and Gastroesophageal Junction (GEJ) Carcinoma
EXPERIMENTALInterventions
Subjects will be treated with BGB A317 200 mg IV on Day 1 during each 21-day cycle. BGB A317 will be administered until disease progression, intolerable toxicity, or treatment discontinuation for any other reason.
Subjects will be treated with cisplatin 80 mg/m² IV on Day 1 during each 21-day cycle. Cisplatinwill be given for up to 6 cycles.
Subjects will be treated with 5-FU 800 mg/m²/day IV using continuous pumping system on Days 1 through 5 during each 21-day cycle. 5-FU will be given for up to 6 cycles.
Subjects will be treated with oxaliplatin 130 mg/m² IV on Day 1 during each 21-day cycle. Oxaliplatin will be administered for up to 6 cycles.
Subjects will be treated with capecitabine 1000 mg/m² orally twice daily (bid) Days 1 through 14 (14 days total) during each 21-day cycle. Capecitabine will be administered until disease progression, intolerable toxicity, or treatment discontinuation for any other reason.
Eligibility Criteria
You may qualify if:
- Pathologically (histologically or cytologically) confirmed diagnosis of either inoperable, locally advanced or metastatic gastric/GEJ adenocarcinoma that is HER2/neu negative or inoperable, locally advanced or metastatic ESCC.
- Note: Archival tumor tissue (paraffin blocks or at least 10 unstained tumor specimen slides) must be available for biomarker analysis. In the absence of archival tumor tissues, a fresh biopsy of a tumor lesion at baseline is mandatory. Subjects may be permitted to enroll on a case-by-case basis after discussion with the Sponsor's medical monitors if paraffin block is not available and fewer than 10 unstained slides can be provided.
- Have received no prior systemic therapy for advanced or metastatic disease. Subject may have received prior neoadjuvant or adjuvant therapy provided it was completed at least 6 months prior to enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Protocol Appendix 3).
- Life expectancy of at least 12 weeks.
- Adequate organ function as indicated by the following screening laboratory values:
- Absolute neutrophil count (ANC) ≥1.5×109/L Platelet count ≥100×109/L Hemoglobin ≥9 g/dL or ≥5.6 mmol/L (Note: Criteria must be met without a transfusion within 4 weeks before sample is drawn).
- Serum creatinine ≤1.5× upper limit of normal (ULN). Serum total bilirubin ≤1.5×ULN. For subjects with Gilbert's syndrome, total bilirubin must be \<3×ULN) Prothrombin time/international normalized ratio (PT/INR) ≤1.5×ULN and activated partial thromboplastin time (aPTT) ≤1.5×ULN unless subject is receiving anticoagulant therapy and PT values is within the intended therapeutic range of the anticoagulant.
- Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN. For subjects with liver metastases, AST and ALT must be ≤5×ULN for subjects with liver metastases
You may not qualify if:
- History of severe hypersensitivity reactions to other mAbs; has known hypersensitivity to fluorouracil (5-FU), cisplatin, or other platinum agents
- Unable to receive a port or peripherally inserted central catheter (PICC) for ESCC subjects
- Prior malignancy active within the 2 years prior to Cycle 1 Day 1, exceptions include the tumor under investigation in this study, and locally recurring cancers that have undergone curative intent treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast.
- Received prior therapies targeting PD-1, PD-L1 or PD-L2 for any reason.
- Have known active brain or leptomeningeal metastases. Subjects with brain metastases are permitted if they are asymptomatic or had previously treated brain metastases that are asymptomatic, radiographically stable and did not require steroid medications for at least 4 weeks prior to Cycle 1 Day 1
- Active autoimmune diseases or history of autoimmune diseases that may relapse should be excluded (Protocol Appendix 5). Subjects with following diseases are allowed to undergo screening: type I diabetes, hypothyroidism managed with hormone replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis or alopecia), controlled celiac disease, or diseases not expected to recur in the absence of external triggering factors.
- Requires systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration to treat a current condition.
- Note:Adrenal replacement doses ≤10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- History of interstitial lung disease, non-infectious pneumonitis except for those induced by radiation therapies; uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.
- Severe chronic or active infection requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
- Uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- Any of the following cardiovascular criteria:
- Current evidence of cardiac ischemia
- Current symptomatic pulmonary embolism
- Acute myocardial infarction ≤6 months prior to Day 1
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BeiGenelead
Study Sites (6)
Fifth Medical Center of Pla General Hospital
Beijing, Beijing Municipality, 100071, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, 430030, China
Northern Jiangsu Peoples Hospital
Yangzhou, Jiangsu, 225001, China
The First Affiliated Hospital of Xian Jiaotong University
Xi'an, Shaanxi, 710061, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003, China
Related Publications (1)
Xu J, Bai Y, Xu N, Li E, Wang B, Wang J, Li X, Wang X, Yuan X. Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2020 Sep 1;26(17):4542-4550. doi: 10.1158/1078-0432.CCR-19-3561. Epub 2020 Jun 19.
PMID: 32561664DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jianmin Xu, MD
The fifth Medical Center, Chinese PLA General Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 8, 2018
First Posted
March 19, 2018
Study Start
July 18, 2017
Primary Completion
March 31, 2019
Study Completion
August 19, 2020
Last Updated
October 23, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
Upon request, and subject to certain criteria, conditions, and exceptions, BeiGene will provide access to individual de-identified participant data from BeiGene-sponsored global interventional clinical studies conducted for medicines for indications that have been approved or in programmes that have been terminated. BeiGene will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data requests can be submitted to medicalinformation@beigene.com.