Clinical Study on the Efficacy and Safety of Iparomlimab and Tuvonralimab Injection Combined With Nab-Paclitaxel in Neoadjuvant Therapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

This clinical study aims to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab Injection (QL1706,an Anti-PD-1/CTLA-4 Combined Antibody) combined with Nab-Paclitaxel in neoadjuvant therapy for patients with locally advanced resectable esophageal squamous cell carcinoma.This study consists of three phases: screening, treatment, and follow-up.Efficacy evaluation and safety monitoring should be performed throughout the study.

Inclusion criteria

• Voluntarily understand and sign the informed consent form for this study.
• Age ≥ 18 years, male or female.
• Histologically or cytologically confirmed thoracic ESCC (Stage T1-2N1-2M0 or T3N0-2M0, according to the AJCC 8th edition).
• ECOG performance status of 0-2.
• No prior treatment for esophageal squamous cell carcinoma.
• Life expectancy ≥ 3 months.
• Adequate function of major organs within 7 days before the first treatment (use of any blood components or cell growth factors within 14 days before enrollment is not permitted):Hemoglobin ≥ 90 g/L; White blood cell count ≥ 3.5 × 10^9/L; Absolute neutrophil count ≥ 1.5 × 10^9/L; Platelets ≥ 80 × 10^9/L; AST and ALT ≤ 2.5 × ULN; Total bilirubin (TBIL) ≤ 1.5 × ULN; Blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN (and creatinine clearance (CCr) ≥ 50 mL/min); Left ventricular ejection fraction (LVEF) ≥ 50%.
• Fertile patients must agree to use reliable contraceptive methods with their partner during the trial and for at least 180 days after the last dose.

Exclusion criteria

• Inability to comply with the study protocol or study procedures.
• Presence of supraclavicular lymph node metastasis.
• Obvious tumor invasion of organs adjacent to the esophageal lesion.
• Evidence of esophagomediastinal or tracheoesophageal fistula found on imaging within 4 weeks before enrollment.
• Allergy or known hypersensitivity to the study drugs or their excipients.
• Anticipated need for systemic corticosteroids or other immunosuppressive therapy during the study treatment period.
• Active autoimmune disease requiring systemic treatment, or a history of autoimmune disease.
• Positive HIV test; positive hepatitis B surface antigen with HBV-DNA > upper limit of normal; active hepatitis C virus (HCV) infection.
• History of esophageal or gastric variceal bleeding due to portal hypertension within 6 months before the first study drug administration; known severe varices on endoscopy within 3 months before the first study drug administration.
• Current interstitial pneumonia or interstitial lung disease, or a history of interstitial pneumonia or interstitial lung disease requiring steroid therapy, or other pulmonary fibrosis, organizing pneumonia that might interfere with the assessment and management of immune-related pulmonary toxicity.
• Evidence of a significant bleeding tendency or other major coagulation disorders.
• Severe cardiovascular or cerebrovascular disease.
• Other malignancies within 5 years before enrollment, except for radically resected basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• History of allogeneic bone marrow transplantation or organ transplantation.
• Patients considered by the investigator to be unsuitable for participation in this study.