This is a prospective, single-arm phase II clinical trial intended to investigate the efficacy of neoadjuvant CTLA-4 monoclonal antibody combined with PD-1 monoclonal antibody plus preoperative chemoradiotherapy for locally advanced esophageal cancer. A total of 44 patients with resectable esophageal squamous cell carcinoma (ESCC) will be enrolled.All enrolled subjects will receive induction therapy with the combination of a CTLA-4 inhibitor and a PD-1 inhibitor. Three weeks afterwards, patients will transition to concurrent chemoradiotherapy combined with PD-1 inhibitor. Intensity-modulated radiotherapy (IMRT) will be delivered at a total dose of 40 Gy in 20 fractions. Radical esophagectomy with two-field thoracic and abdominal lymph node dissection will be performed 6-8 weeks after completion of chemoradiotherapy.The primary objective of this trial is to evaluate the efficacy and safety of the triplet regimen consisting of CTLA-4 inhibitor plus PD-1 inhibitor combined with preoperative chemoradiotherapy in locally advanced esophageal cancer, so as to further optimize the multimodal therapeutic strategy for esophageal cancer.
Histologically confirmed resectable thoracic esophageal squamous cell carcinoma (ESCC); pretreatment clinical stage of T1-4aN1-3M0 or T3-4aN0M0 per the 8th edition of UICC staging system.
Treatment-naive patients without prior anti-tumor therapy.
Expected survival duration > 6 months.
Aged between 18 and 75 years, either male or female.
Patients who have received prior anti-tumor therapies including chemotherapy, radiotherapy, surgery, immunotherapy, etc.
Patients with known or suspected hypersensitivity to any components of CTLA-4 inhibitors, sintilimab or other monoclonal antibodies, as well as chemotherapeutic agents (nab-paclitaxel and cisplatin).
Patients with pre-existing hemorrhagic disorders.
Patients with unresectable disease due to other uncontrollable conditions.
Single group
Ipilimumab (1mg/kg)
DrugChemotherapy and dual immunotherapy agents Anti-CTLA-4 monoclonal antibody (IBI310): 1 mg/kg via intravenous infusion on Day 1 (D1);
Sinitilimab
DrugSintilimab (anti-PD-1 monoclonal antibody) will be administered at a dose of 200 mg via intravenous infusion on Day 1, Day 22 and Day 43.
Nab-paclitaxel + Cisplatin
DrugNab-paclitaxel: 75 mg/m² via intravenous infusion on D22, D29, D36 and D43; Cisplatin: 25 mg/m² via intravenous infusion on D22, D29, D36 and D43.
IMRT combine with cisplatin concurrent chemotherapy
RadiationIntensity-modulated radiotherapy (IMRT) will be adopted with a total dose of 40 Gy in 20 fractions. Radiotherapy starts on Day 22, administered 5 times per week and completed within 4 weeks.
Pathologic complete response rate
No malignant tumor cells were detected in the removed specimens including primary tumor and lymph nodes
R0 resection rate
The persentage of patients who under complete resection
Tumor Regression Grade
Progression free survival
Progression free survival is defined as the time from randomization until objective tumor progression or death
Overall survival
Overall survival will be calculated from the date of randomization and an event registered on the date of death from those with no death recorded on the day the database is frozen,will be censored on the date of last follow up
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