Application of Toripalimab as Adjuvant Therapy After Esophageal Cancer Surgery: A Multicenter Clinical Trial

This is a prospective, multicenter, multi-cohort Phase III clinical study. It primarily enrolls high-risk recurrent esophageal cancer patients who have achieved R0 resection after undergoing neoadjuvant chemoimmunotherapy. Eligible patients are stratified into two cohorts based on pathological lymph node status: Cohort A (ypN+ cohort) and Cohort B (ypN0 cohort).

Interventions and Treatment Schedule Cohort A (ypN+ cohort): Patients receive toripalimab monotherapy as consolidation/maintenance treatment.

Dosage: Toripalimab 240 mg. Administration: Every 3 weeks per cycle. Duration: Up to 17 cycles, with a total treatment period not exceeding one year.

Cohort B (ypN0 cohort): Patients are randomized 1:1 into two groups:

Experimental Group: Receives toripalimab monotherapy as consolidation/maintenance treatment (same dosage and schedule as Cohort A).

Control Group: Undergoes postoperative observation only. Follow-up and Assessments Disease Evaluation: Assessments including chest + upper abdominal contrast-enhanced CT + neck contrast-enhanced CT are performed every 3 months for 2 years, then every 6 months until the 5th year. PET-CT, chest MRI, gastroscopy, and bronchoscopy are conducted when necessary.

Safety Monitoring: Adverse events (AEs) are monitored throughout the study and graded according to CTCAE v5.0. Safety follow-up is performed for all subjects who received the study treatment, including those who discontinued early.

Inclusion criteria

• Patients voluntarily participate in this study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up.
• Initial patients are those with resectable or potentially resectable (T1 N1-3 M0 or T2-3 N0-3 M0) thoracic segment esophageal squamous cell carcinoma (8th UICC-TNM staging); who have undergone surgical resection after 2 cycles of immunotherapy combined with chemotherapy and achieved R0 resection.
• Age 18 to 75 years.
• Preoperative examinations of various organ functions indicate no surgical contraindications.
• The following laboratory tests confirm that bone marrow, liver, and kidney functions meet the study requirements:

Hemoglobin ≥ 90 g/L; White blood cell count ≥ 4.0 × 10⁹/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Total bilirubin ≤ 1.5 times the upper limit of normal (ULN); ALT and AST ≤ 2.5 times ULN; International normalized ratio (INR) of prothrombin time ≤ 1.5 times ULN, and activated partial thromboplastin time within the normal range; Creatinine ≤ 1.5 times ULN.

• No postoperative chemotherapy, radiotherapy, or hormone therapy for malignant tumors has been administered; no history of other malignancies, excluding prostate cancer patients who have received hormone therapy and achieved disease-free survival (DFS) for over 5 years.
• Physical status ECOG score 0 to 1.
• Women of childbearing potential must agree to use contraceptive measures (e.g., intrauterine device, contraceptive pills, or condoms) during the study and for 6 months after study completion; serum or urine pregnancy test within 7 days before study enrollment must be negative, and patients must be non-lactating; men must agree to use contraceptive measures during the study and for 6 months after study completion.

Exclusion criteria

• Patients with double primary cancers;
• Patients with infections requiring treatment;
• Patients requiring continuous systemic corticosteroid therapy (Note: Replacement therapy (e.g., for thyroid insufficiency, insulin therapy, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic therapy and is permitted);
• Patients with unstable angina within 3 months or myocardial infarction within 6 months;
• Patients with psychiatric disorders;
• Patients with existing or concurrent hemorrhagic disorders;
• Female patients who are pregnant or breastfeeding;
• Patients with bronchial asthma requiring intermittent use of bronchodilators or medical intervention;
• Patients who have used immunosuppressive agents prior to enrollment due to comorbid conditions, with a dose equivalent to ≥10mg/day of oral prednisone sustained for more than 2 weeks;
• Patients with abnormal coagulation function (PT > 16s, APTT > 53s, TT > 21s, Fib < 1.5g/L), bleeding tendency, or those receiving thrombolytic or anticoagulant therapy;
• Patients with pre-existing or concurrent pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, severe pulmonary impairment, etc.;
• Patients with autoimmune diseases, immunodeficiency, or organ transplantation;
• Patients with active Hepatitis B or Hepatitis C infection.