A Prospective, Single-Arm Phase II Clinical Study of Neoadjuvant Chemoradiotherapy Combined With CTLA-4 Monoclonal Antibody Plus PD-1 Monoclonal Antibody for Locally Advanced Esophageal Cancer
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.
• Adequate function of major vital organs meeting the following laboratory criteria:
∙ White blood cell (WBC) ≥4.0×10⁹/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L;
‣ Platelet count ≥100×10⁹/L;
‣ Hemoglobin ≥9 g/dL;
‣ Serum albumin ≥2.8 g/dL;
‣ Total bilirubin ≤1.5 × ULN; ALT, AST and/or ALP ≤2.5 × ULN;
‣ Serum creatinine ≤1.5 × ULN, or creatinine clearance \>60 mL/min.
• Eastern Cooperative Oncology Group (ECOG) PS score: 0-1.
• Capable of understanding the study protocol and signing written informed consent.
• Absence of severe complications including active massive gastrointestinal hemorrhage, perforation, jaundice, bowel obstruction, or non-malignant fever \>38℃.
• Female and male patients of childbearing potential must use effective contraception throughout relevant study period.
⁃ Good treatment compliance and availability for scheduled follow-up of efficacy and adverse events per study protocol.