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

BeiGene

Status and phase: Completed; Phase 3

Conditions: Esophageal Squamous Cell Carcinoma (ESCC)

Treatments: Drug: Cisplatin; Drug: Placebo; Drug: Fluorouracil (5-FU); Drug: Oxaliplatin; Drug: Paclitaxel; Drug: Capecitabine; Biological: Tislelizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03783442

BGB-A317-306

JapicCTI-194741 (Registry Identifier)

2018-000587-28 (EudraCT Number)

CTR20181013 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 649 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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649 participants in 2 patient groups

Tislelizumab + Chemotherapy

Experimental group

Description:

Participants received tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons. Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil \[750-800 mg/m² intravenously on Days 1-5\] or capecitabine \[1000 mg/m² orally twice daily on Days 1-14\]) or paclitaxel (175 mg/m² intravenously on Day 1).

Treatment:

Biological: Tislelizumab

Drug: Capecitabine

Drug: Paclitaxel

Drug: Oxaliplatin

Drug: Fluorouracil (5-FU)

Drug: Cisplatin

Placebo + Chemotherapy

Active Comparator group

Description:

Participants received placebo administered IV on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons. Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil \[750-800 mg/m² intravenously on Days 1-5\] or capecitabine \[1000 mg/m² orally twice daily on Days 1-14\]) or paclitaxel (175 mg/m² intravenously on Day 1).

Treatment:

Drug: Capecitabine

Drug: Paclitaxel

Drug: Oxaliplatin

Drug: Placebo

Drug: Fluorouracil (5-FU)

Drug: Cisplatin