A Study Investigating Alternate Schedules of Tislelizumab Plus Chemotherapy in Japanese Patients With First-line Advanced ESCC

Official title

A Phase 2 Study of Tislelizumab Administered With Alternative Dosing Schedules Plus Chemotherapy as First-line Treatment in Japanese Patients With Unresectable Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Overview

The purpose of this study is to evaluate the pharmacokinetic (PK) profile, safety, and efficacy of tislelizumab administered once every 2 weeks (Q2W) or once every 4 weeks (Q4W) in combination with chemotherapy as first-line treatment in Japanese participants with previously untreated, unresectable locally advanced, or metastatic esophageal squamous cell carcinoma (ESCC).

Detailed description

Esophageal squamous cell carcinoma (ESCC) is a type of cancer that starts in the flat cells lining the inside of the esophagus (food pipe), the tube that carries food from the mouth to the stomach. In advanced stages, the cancer spreads to nearby tissues or other parts of the body.

Tislelizumab is used to block the programmed cell death protein-1 pathway so that immune system cells (T-cells) can better protect the body from infection and find tumor cells to attack. Tislelizumab may be used in combination with other therapies as a promising approach with potential therapeutic benefits to treat participants with cancer.

The purpose of this study is to test whether tislelizumab is safe and can help treat esophageal squamous cell carcinoma. The main goal of the study is to ensure that the treatments are safe by monitoring side effects and to understand how well participants respond to the treatment and whether their cancers shrink or disappear.

This study consists of two treatment groups. The first 10 participants will be randomly assigned (by chance, like flipping a coin) to one of two treatment groups; after that all participants will be assigned to Group 2.The study is open label, which means that the participants and the study doctors will know what treatment they receive.

Group 1: Tislelizumab every 2 weeks plus FOLFOX chemotherapy (oxaliplatin, leucovorin, and 5-FU) given by intravenous (IV) infusion every 2 weeks

Group 2: Tislelizumab every 4 weeks plus FOLFOX chemotherapy (oxaliplatin, leucovorin, and 5-FU) given by intravenous (IV) infusion every 2 weeks

The study will enroll approximately 30 participants in Japan with ESCC. The overall time to participate in this study is approximately 1 year. Participants will make regular visits to the clinic for treatment, health checks, blood tests, and for tumor and imaging tests.

Interventions

• Drug Tislelizumab
  Administered by intravenous infusion
• Drug Oxaliplatin
  Administered by intravenous infusion
• Drug Leucovorin
  Administered by intravenous infusion
• Drug 5-fluorouracil (5-FU)
  Administered by intravenous infusion

Primary outcome measures

• Serum Concentrations of Tislelizumab at Specified Time Points [Time frame: Approximately 12 months]
• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Approximately 12 months]
• Overall Response Rate (ORR)Assessed by Independent Review Committee (IRC) [Time frame: Approximately 12 months]

Secondary outcome measures (1)

• Progression-Free Survival (PFS) Rate at 6 Months [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• Able to provide written informed consent by the participant or by the participants' legally acceptable representative and can understand and agree to comply with the requirements of the study
• Histologically confirmed, unresectable locally advanced, recurrent or metastatic ESCC not amenable to curative approaches such as definitive chemoradiation or surgery.
• No previous systemic therapy for unresectable locally advanced, recurrent or metastatic ESCC
• At least 1 measurable lesion per RECIST v1.1 as determined by investigator
• Eastern Cooperative Oncology Group (ECOG) Performance Status score ≤ 1
• Adequate organ function as indicated by the laboratory values ≤ 14 days prior to the first dose of study drugs
• Females of childbearing potential must have a negative urine or serum pregnancy test≤ 7 days prior to the first dose of study drugs and be willing to use a highly effective method of birth control for the duration of the study until at least 120 days after the last dose of tislelizumab. Further contraception requirements after completing chemotherapy should follow the approved product labeling for each specific cytotoxic agent

Exclusion criteria

• Participants who are unable to comply with the requirements of the protocol
• Participants with evidence of esophageal or gastroesophageal perforation or fistula ( esophageal/bronchial or esophageal/aorta), or complete esophageal obstruction not amenable to treatment within 6 months prior to the first dose of study drugs
• Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention) and/or diuretics within 7 days prior to the first dose of study drugs (the cytological confirmation of any effusion is permitted)
• Have an estimated life expectancy < 3 months, per the judgment of the investigator
• Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis
• Prior therapy with anti-programmed death protein-1 (anti-PD-1), anti-programmed death protein ligand-1(anti-PD-L1), anti-programmed death protein ligand- 2 (anti-PD-L2), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07733180 · BGB-A317-216

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗