A Study of Chemoradiation in Combination with Tislelizumab As First Line Treatment in Participants with Advanced Esophageal Squamous Cell Carcinoma

Wuhan University

Status and phase: Enrolling; Phase 3

Conditions: Esophageal Squamous Cell Carcinoma

Treatments: Drug: Cisplatin; Drug: Tislelizumab; Radiation: Intensity-modulated radiotherapy (IMRT); Drug: Nab paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT05919030

WDRY2023-K088

Details and patient eligibility

About

This study is a multicentre, randomised, parallel-controlled, open-label, 3 phase clinical trial. The subjects were untreated, unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma with low PD-L1 expression. Patients were randomly assigned to receive chemoradiation or chemotherapy in combination with Tislelizumab at a ratio of 1: 1. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We hypothesized that in advanced esophageal squamous cell carcinoma patients with low PD-L1 expression, chemoradiation versus chemotherapy in combination with Tislelizumab will significantly improve PFS.

Enrollment: 155 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subjects must have histologically confirmed squamous cell carcinoma of esophagus (per AJCC 8th edition).
2. Subjects must have unresectable advanced, recurrent or metastatic ESCC.
3. Subjects must not be amenable to curative approaches such as definitive chemoradiation and/or surgery.
4. PD-L1 expression (CPS) is less than 10.
5. No prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease.
6. ECOG Performance Status of 0 or 1.
7. Subjects must have at least one measurable lesion by CT or MRI per RECIST 1.1 criteria; radiographic tumor assessment must be performed within 28 days prior to randomization.
8. Subjects must have adequate organ and bone marrow function.

Exclusion criteria

1. Presence of tumor cells in the brain or spinal cord which are symptomatic or require treatment.
2. Active known or suspected autoimmune disease.
3. Any serious or uncontrolled medical disorder or active infection.
4. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
5. Any positive test result for hepatitis B or C indicating acute or chronic infection and/or detectable virus.
6. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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155 participants in 2 patient groups

Chemoradiation + Tislelizumab

Experimental group

Description:

Intensity-modulated radiotherapy (IMRT): Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy During concurrent radiation therapy: Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 75 mg/m² IV QW Drug: Cisplatin 25 mg/m² IV QW During consolidation therapy: Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W

Treatment:

Drug: Nab paclitaxel

Radiation: Intensity-modulated radiotherapy (IMRT)

Drug: Cisplatin

Drug: Tislelizumab

Chemotherapy + Tislelizumab

Active Comparator group

Description:

Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W

Treatment:

Drug: Nab paclitaxel

Drug: Cisplatin

Drug: Tislelizumab