A Study of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma

• ClinicalTrials.gov Identifier: NCT03783442
• Recruitment Status: Active, not recruiting
• First Posted: December 21, 2018
• Last Update Posted: May 2, 2022
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: December 18, 2018
• First Posted Date: December 21, 2018
• Last Update Posted Date: May 2, 2022
• Actual Study Start Date: December 11, 2018
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 26, 2022)

Overall Survival (OS) [ Time Frame: Up to approximately 40 months from date of the first participant randomization ]

OS is defined as the time from the date of randomization until the date of death due to any cause

Original Primary Outcome Measures (submitted: December 19, 2018)

• PFS - defined as the time from the date of randomization to the date of first documentation of disease progression assessed by BIRC per RECIST v1.1 or death, whichever occurs first [ Time Frame: Approximately 31 months from date of the first patient randomization ]
• OS - defined as the time from the date of randomization until the date of death due to any cause [ Time Frame: Approximately 31 months from date of the first patient randomization ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: April 26, 2022)

• Progression-Free Survival (PFS) [ Time Frame: Approximately 40 months from date of the first participant randomization ]
  PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first
• Objective Response Rate (ORR) [ Time Frame: Approximately 40 months from date of the first participant randomization ]
  ORR is defined as the proportion of participants whose best overall response (BOR) is complete response (CR) or partial response (PR) assessed by the investigator per RECIST v1.1
• Overall survival (OS) in the PD-L1 score ≥ 10% subgroup [ Time Frame: Approximately 40 months from date of the first participant randomization ]
  OS is defined as the time from the date of randomization until the date of death due to any cause
• Duration of Response (DOR) [ Time Frame: Approximately 40 months from date of the first participant randomization ]
  DOR is defined as the time from the first determination of an objective response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever comes first
• Health-Related Quality of Life (HRQoL) assessment of the participant's overall health status using European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30) [ Time Frame: Approximately 40 months from date of the first participant randomization ]
• Health-Related Quality of Life (HRQoL) assessment of the participant's overall health status using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer specific module (EORTC QLQ-OES18) [ Time Frame: Approximately 40 months from date of the first participant randomization ]
• Health-Related Quality of Life (HRQoL) assessment of the participant's overall health status using the generic health state instrument European Quality of Life-5 Dimensions (EuroQol 5D EQ-5D-5L) [ Time Frame: Approximately 40 months from date of the first participant randomization ]
• Number of participants experiencing Adverse Events (AEs) [ Time Frame: Approximately 40 months from date of the first participant randomization ]

Original Other Pre-specified Outcome Measures (submitted: December 19, 2018)

• ORR - defined as the proportion of patients whose best overall response (BOR) is complete response (CR) or partial response (PR) assessed by BIRC per RECIST v1.1 [ Time Frame: Approximately 31 months from date of the first patient randomization ]
• DOR- defined as the time from the first determination of an objective response until the first documentation of progression assessed by BIRC per RECIST v1.1 or death, whichever comes first [ Time Frame: Approximately 31 months from date of the first patient randomization ]
• Health-Related Quality of Life (HRQoL) assessment of the patient's overall health status using European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30). [ Time Frame: Approximately 31 months from date of the first patient randomization ]
• Health-Related Quality of Life (HRQoL) assessment of the patient's overall health status using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer specific module (EORTC QLQ-OES18). [ Time Frame: Approximately 31 months from date of the first patient randomization ]
• Health-Related Quality of Life (HRQoL) assessment of the patient's overall health status using the generic health state instrument European Quality of Life- 5 Dimensions (EuroQol 5D EQ-5D-5L). [ Time Frame: Approximately 31 months from date of the first patient randomization ]
• The incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 [ Time Frame: Approximately 31 months from date of the first patient randomization ]

Descriptive Information

• Brief Title: A Study of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
• Official Title: A Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Efficacy and Safety of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First-Line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
• Brief Summary: The purpose of this study is to evaluate the efficacy and safety of Tislelizumab as first line treatment in combination with chemotherapy in participants with advanced unresectable/metastatic esophageal squamous cell carcinoma (ESCC).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Esophageal Squamous Cell Carcinoma (ESCC)

Intervention

• Drug: Cisplatin
  60 to 80 mg/m^2 intravenously (IV) on Day 1 once every 3 weeks (Q3W)
• Drug: Oxaliplatin
  130 mg/m^2 IV on Day 1 Q3W
• Drug: Fluorouracil (5-FU)
  750 to 800 mg/m^2 IV continuous infusion over 24 hours daily on Days 1 to 5 Q3W
• Drug: Capecitabine
  1000 mg/m^2 orally (PO) twice daily (BID) on Days 1 to 14 Q3W
• Drug: Paclitaxel
  175 mg/m^2 IV on Day 1 Q3W
• Drug: Tislelizumab
  200 mg IV Q3W
• Drug: Placebo
  Placebo to match Tislelizumab

Study Arms

• Experimental: Tislelizumab + chemotherapy

  Tislelizumab administered with chemotherapy doublet:

  Doublet A: Cisplatin or Oxaliplatin plus Fluorouracil (5-FU); Doublet B: Cisplatin or Oxaliplatin plus Capecitabine; Doublet C: Cisplatin or Oxaliplatin plus Paclitaxel

  Interventions:

  • Drug: Cisplatin
  • Drug: Oxaliplatin
  • Drug: Fluorouracil (5-FU)
  • Drug: Capecitabine
  • Drug: Paclitaxel
  • Drug: Tislelizumab
• Active Comparator: Placebo + chemotherapy

  Placebo administered with chemotherapy doublet:

  Doublet A: Cisplatin or Oxaliplatin plus Fluorouracil (5-FU); Doublet B: Cisplatin or Oxaliplatin plus Capecitabine; Doublet C: Cisplatin or Oxaliplatin plus Paclitaxel

  Interventions:

  • Drug: Cisplatin
  • Drug: Oxaliplatin
  • Drug: Fluorouracil (5-FU)
  • Drug: Capecitabine
  • Drug: Paclitaxel
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 28, 2021): 649
• Original Estimated Enrollment (submitted: December 19, 2018): 480
• Estimated Study Completion Date: September 30, 2023
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Participants with unresectable, locally advanced recurrent or metastatic ESCC who have Stage IV unresectable ESCC at first diagnosis (ie, Stage IV disease at the original diagnosis of ESCC) or who have unresectable, locally advanced recurrent or metastatic disease with at least a 6-month treatment-free interval, if prior definitive therapy (chemotherapy, chemo-radiation therapy or surgery) was given.

Key Inclusion Criteria:

1. Pathologically (histologically) confirmed diagnosis of ESCC
2. Stage IV unresectable ESCC at first diagnosis OR unresectable, locally advanced recurrent or metastatic disease (per American Joint Committee on Cancer 7th Edition), if there is prior neoadjuvant/adjuvant therapy with platinum-based chemotherapy, a treatment-free interval of at least 6 months is required.

Key Exclusion Criteria:

1. Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation
2. Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC
3. Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2
4. Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta)
5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention)
6. Evidence of complete esophageal obstruction not amenable to treatment
7. Unintentional weight loss ≥ 5% within one month prior to randomization or Nutritional Risk Index (NRI) < 83.5 per investigator's choice
8. Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator.
9. Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is ≥ 500 IU/mL or participants with active hepatitis C virus (HCV)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, China, Czechia, France, Germany, Italy, Japan, Korea, Republic of, Poland, Romania, Russian Federation, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03783442
• Other Study ID Numbers: BGB-A317-306; 2018-000587-28 ( EudraCT Number ); CTR20181013 ( Other Identifier: Center for drug evaluation, CFDA ); JapicCTI-194741 ( Registry Identifier: Japic )
• Has Data Monitoring Committee: Yes

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

• Plan to Share IPD: Yes

• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Liyun Li, MD; BeiGene

• PRS Account: BeiGene
• Verification Date: April 2022