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Esophageal Squamous Cell Carcinoma, Gastric Carcinoma, Gastroesophageal Junction CarcinomaPhase 2NCT03469557

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 study testing Tislelizumab, Cisplatin and 5-FU in people with Esophageal Squamous Cell Carcinoma, Gastric Carcinoma, Gastroesophageal Junction Carcinoma, run by BeiGene at 6 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Tislelizumab, Cisplatin and 5-FU
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
6 sitesChina
Study dates
18 Jul 2017to 19 Aug 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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.
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  • 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
  • Heart failure of New York Heart Association Classification III or IV(Protocol Appendix 6) ≤6 months prior to Day 1
  • Grade 2 or higher ventricular arrhythmia ≤6 months prior to Day 1
  • Cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤6 months prior to Day 1
  • Has a history of alcohol or drug abuse or dependence
  • Known history of Human Immunodeficiency Virus (HIV).
  • Untreated chronic hepatitis B viral (HBV) infection or chronic HBV carrier with HBV DNA ≥200 IU/mL (or 1000 copies/mL), or active hepatitis C virus (HCV) should be excluded. Note: subjects with inactive HBV surface antigen (HBsAg) carrier, active HBV infection with sustained anti-HBV suppression (HBV DNA <200 IU/mL or 1000 cps/mL), and subjects whose HCV has been cured can be enrolled.
  • Underlying medical conditions that, in the investigator's opinion, will be unfavorable for the administration of study drug or affect communication regarding drug toxicity or adverse events. Note: subjects whose compliance during this study is considered by the investigator to be questionable should be excluded.
  • Has been administered a live vaccine within 4 weeks prior to Cycle1 Day 1.
  • Administered a monoclonal antibody within 4 weeks for any reason prior to study Day 1 or who has not recovered (i.e., Grade 1 or lower at baseline) from adverse events due to agents administered more than 4 weeks earlierMedical history of dihydropyrimidine dehydrogenase deficiency (DPD). Note: subjects do not need to be tested for DPD at screening.
  • Medical history of dihydropyrimidine dehydrogenase deficiency (DPD). Note: subjects do not need to be tested for DPD at screening.
  • Has received radiotherapy or treatment with an investigational agent within 14 days prior to Cycle 1 Day 1
  • Major surgical procedure other than for diagnostic biopsy of tumor tissue for this study or placement of a venous access device within 28 days prior to study drug administration.
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

China6 sites

  • Fifth Medical Center of Pla General Hospital

    Beijing, Beijing Municipality, 100071

  • The First Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310003

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang, 150000

  • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

    Wuhan, Hubei, 430030

  • The First Affiliated Hospital of Xian Jiaotong University

    Xi'an, Shaanxi, 710061

  • Northern Jiangsu Peoples Hospital

    Yangzhou, Jiangsu, 225001

Other trials in China

About this study

Official title: 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

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.

Read the detailed description

The study includes an initial phase during which 6 subjects will be enrolled in each cohort (ESCC and GC/GEJ carcinoma). Safety data will be reviewed by a Safety Monitoring Committee (SMC) after the first 6 subjects in a cohort have completed at least 1 cycle (21 days) of treatment. During the initial phase, subjects who discontinue for a reason unrelated to safety before completing Cycle 1 will be replaced. If there are no new, significant or severe, safety signals detected, the enrollment will be expanded up to approximately 15 subjects per cohort (treatment expansion). During the treatment expansion, subjects will not be replaced for any reason.

In the ESCC cohort, subjects will be treated with BGB A317 200 mg IV on Day 1, cisplatin 80 mg/m² IV on Day 1, and 5-FU 800 mg/m²/day IV using continuous pumping system on Days 1 through 5 during each 21-day cycle. Cisplatin and 5-FU will be given for up to 6 cycles and BGB A317 will be administered until disease progression, intolerable toxicity, or treatment discontinuation for any other reason.

In the GC and GEJ carcinoma cohort, subjects will be treated with BGB A317 200 mg IV on Day 1, oxaliplatin 130 mg/m² IV on Day 1, and capecitabine 1000 mg/m² orally twice daily (bid) Days 1 through 14 (14 days total) during each 21-day cycle. Oxaliplatin will be administered for up to 6 cycles and capecitabine and BGB A317 will be administered until disease progression, intolerable toxicity, or treatment discontinuation for any other reason.

Medical subject headings
Esophageal Squamous Cell Carcinoma, Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TislelizumabDrug

    Also called BGB-A317

    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.

  • CisplatinDrug

    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.

  • 5-FUDrug

    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.

  • OxaliplatinDrug

    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.

  • CapecitabineDrug

    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.

Study groups in NCT03469557
Study groupRoleWhat they receive
Esophageal Squamous Cell Carcinoma (ESCC)ExperimentalNot described
Receives: Drug: Tislelizumab; Drug: Cisplatin; Drug: 5-FU
Gastric (GC) and Gastroesophageal Junction (GEJ) CarcinomaExperimentalNot described
Receives: Drug: Tislelizumab; Drug: Oxaliplatin; Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The objective response rate (ORR) as assessed by RECIST, Version 1.1

    Measured: Through study completion, an average of 9 months

  2. The Duration of Response (DoR) as assessed by RECIST, Version 1.1

    Measured: Through study completion, an average of 9 months

  3. The Disease Control Rate (DCR) as assessed by RECIST, Version 1.1

    Measured: Through study completion, an average of 9 months

  4. The Progression-Free Survival (PFS) as assessed by RECIST, Version 1.1

    Measured: Through study completion, an average of 9 months

  5. Pharmacokinetic evaluations: include but not limited to minimum observed serum concentration (Ctrough) for BGB-A317.

    Measured: Through study completion, an average of 10 months

  6. Host immunogenicity: BGB-A317 anti-drug antibody (ADA)

    Measured: Through study completion, an average of 10 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2018
  2. Study start18 Jul 2017
  3. Primary completion31 Mar 2019
  4. Study completion19 Aug 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03469557
Sponsor's protocol ID
BGB-A317-205
Other IDs
CTR20170515
Status last verified
Oct 2024
First submitted
8 Feb 2018
Last updated
23 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 32561664

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tislelizumab, Cisplatin and 5-FU in people with Esophageal Squamous Cell Carcinoma, Gastric Carcinoma, Gastroesophageal Junction Carcinoma, run by BeiGene at 6 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The objective response rate (ORR) as assessed by RECIST, Version 1.1 (time frame: Through study completion, an average of 9 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03469557, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2024; AzTrials last refreshed its copy on 7 Nov 2026.

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