The investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable esophageal squamous cell carcinoma (ESCC).
Host immunity is critical to the development and progression of tumor. PD-1 is the co-inhibitory receptor in many immunity cells while PD-L1, the ligands for PD-1, is expressed in tumor cell and is associated with prognosis. Previous studies have shown that anti-PD-1/PD-L1 antibody had durable responses in patients with advanced malignant tumors such as melanoma, renal cell cancer, lung cancer and esophagus cancer. SHR-1316 (Hengrui Medicine, China), anti-PD-L1 antibody, could induce the elevated secretion of interferon (IFN)-α and showed significant tumor-suppression effect in vivo. The phase III clinical trial on the SHR-1316 versus placebo combines with carboplatin and etoposide in the patients with small cell lung cancer is currently being studied (SHR-1316-III-301). Esophagus cancer usually has a poor prognosis and esophagus squamous cell carcinoma (ESCC) is the main histological type in China. Combination with operation and neoadjuvant therapy including radiotherapy or/and chemotherapy is considered the standard therapy for local advanced esophagus cancer. However, no studies focused on the neoadjuvant immunotherapy in resectable esophagus have been reported. Therefore, the investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable ESCC. The primary objectives included the tumor regression grade, adverse event, safety of operation, complications and 30-day mortality. Our study will also explore the relation of tumor immune milieu, circulating immune cells, soluble factors, circulating tumor cell in the patients. Data from our study will provide the basis for further prospective clinical trials (Phase III). Finally, the investigators aim to discover the biomarkers of response and toxicity to allow patients with ESCC derive more benefit from immunotherapy and minimize the risk of toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Neoadjuvant therapy with immunoreagent (PD-L1 antibody SHR-1316) for resectable oesophageal squamous cell carcinoma
180 Fenglin Road
Shanghai, China
RECRUITINGObjective Response
The primary endpoint is objective response (according to the Response Evaluation Criteria In Solid Tumors, version 1.1).
Time frame: Through the study completion, an average of 12 weeks
Adverse events and treatment-related adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Through the study completion, an average of 12 weeks
Correlation between genetic profile and tumor response
Genetic profile (assessed by whole exome sequencing, T-cell receptor sequencing, RNA sequencing) will be correlated with tumor objective response
Time frame: Through the study completion, an average of 12 weeks
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