Sintilimab Injection Combination with Concurrent Chemoradiotherapy (cCRT) in Patients with Localized Esophageal Squamous Cell Carcinoma: A Prospective, Multi-Center, Single-Arm Trial in Progress

Abstract

Esophageal cancer had accounted for the sixth highest incidence and the fourth highest death rate in China. The predominant histological subtype is esophageal squamous cell carcinoma (ESCC). At initial diagnosis, more than half of patients with ESCC are unfit for surgery. An accepted alternative to surgery is concurrent chemoradiotherapy (cCRT); however, many patients experience local recurrence or distant metastasis after cCRT. Therefore, innovative therapies are needed. Sintilimab is a fully human IgG4 monoclonal antibody, exhibiting the highest affinity for human PD-1 and a lower off-rate, the PD-1 receptor occupancy of sintilimab on circulating T cells is superior. In previous studies, sintilimab, alone and in combination with chemotherapy, was generally well tolerated and had antitumor activity in patients with advanced ESCC. This prospective, single-arm study (NCT04602013) is designed to explore the efficacy of Sintilimab in combination with cCRT. Eligible patients have histologically confirmed localized ESCC for whom cCRT is suitable and surgery is unsuitable/ declined; patients couldn't have received prior chemoradiotherapy. Approximately 53 Chinese patients from 5 centers will be to receive sintilimab (body weight <60kg: 3mg/kg IV Q3W; body weight ≥60kg: 200mg IV Q3W) in combination with cisplatin (25 mg/m2 IV on Days 1-3 of each 3-week cycle) plus paclitaxel for injection (albumin bound) (180 mg/m2). and radiotherapy at a total dose of 60Gy. Duration of treatment will be up to 12 months for sintilimab, including two cycles for concurrent administration of chemotherapy and radiotherapy. Progression-free survival (PFS), assessed by a Blinded Independent Review Committee per RECIST v1.1, is the primary endpoint of the study. Secondary efficacy endpoints include overall response rate, duration of response, and overall survival. Incidence and severity of adverse events (CTCAE V5.0) and patient-reported outcomes of health-related quality of life are additional secondary endpoints. A total of 17 patients have completed sintilimab injection combination with concurrent chemoradiotherapy,17/53 (32%). Objective response rate (ORR) 62.5% and a median progression free survival (mPFS) 17 months. 1-year overall survival (OS) 88.2%. The most common AEs included granulocytopenia (43.7%), thrombo -cytopenia (56.2%), radiation esophagitis (50%), nausea and vomiting (50%), and immune pneumonia (18.7%). Of these AEs greater than grade 3 granulocytopenia (25.0%), thrombocytopenia (35.0%), radiation esophagitis (12.5%), and nausea and vomiting (31.3%), and one patient developed grade 3 immune pneumonia (6.2%), which recovered with treatment. The treatment of sintilimab with CCRT is safe and effective for localized ESCC patients, even with high-dose radiotherapy (60Gy). This study may help to address the unmet need for new therapeutic options for patients with localized ESCC.