Ipromlimab and Tuvonralimab Combined With Albumin-Bound Paclitaxel and Nedaplatin as Neoadjuvant Therapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

Inclusion Criteria:

* No prior treatment for the condition.
* Diagnosis of squamous cell carcinoma confirmed by endoscopic biopsy, with agreement to provide a pre-treatment tissue sample.
* Patients must have thoracic esophageal cancer only. The primary site is determined by the center of the mass:

  1. Upper thoracic esophagus: From the thoracic inlet to the lower border of the aortic arch, corresponding to 20-25 cm from the incisors by endoscopy.
  2. Middle thoracic esophagus: From the lower border of the aortic arch to the level of the inferior pulmonary veins, corresponding to 25-30 cm from the incisors by endoscopy.
  3. Lower thoracic esophagus: From the level of the inferior pulmonary veins to the stomach, including the gastroesophageal junction, corresponding to 30-40 cm from the incisors by endoscopy.
* Deemed to have potentially resectable disease, with clinical stage III (cT3N1M0 to cT1-3N2M0) according to the UICC/AJCC TNM Staging System, 8th Edition.
* Age ≥18 years and ≤75 years.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* Adequate organ function, meeting the following criteria (without transfusion or hematopoietic growth factor support within 14 days prior to the first dose):

  1. Hematology: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; Platelet count ≥100 × 10⁹/L; Hemoglobin ≥9.0 g/dL.
  2. Biochemistry: Total bilirubin \<1.5 × upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 × ULN; Serum creatinine ≤1.5 × ULN or calculated creatinine clearance ≥50 mL/min.
  3. Coagulation: International normalized ratio (INR) ≤1.5; Activated partial thromboplastin time (APTT) ≤1.5 × ULN.
* Male and female participants of childbearing potential must agree to use medically approved contraceptive methods during the study period and for 6 months after the last dose of the study drug(s).
* The subject is capable of understanding, able to comply with study and follow-up procedures, and voluntarily signs a written informed consent form.

Exclusion Criteria:

* Disease assessed as unresectable based on imaging such as contrast-enhanced CT of the chest/abdomen, neck lymph node ultrasound, whole-body PET-CT scan (optional), or endobronchial ultrasound (EBUS) (optional). This includes: the presence of bulky lymph nodes (≥7 suspicious lymph nodes), multi-station lymph node involvement (≥2 stations of suspicious lymph nodes), or distant metastasis.
* History of other malignancies (except for cervical carcinoma in situ or cured, localized basal cell carcinoma of the skin).
* History of autoimmune diseases.
* Recent or current use of corticosteroids or immunosuppressants.
* History of severe hypersensitivity to antibody-based drugs.
* History of chronic or recurrent autoimmune diseases.
* History of interstitial lung disease, pulmonary fibrosis, diverticulitis, or systemic ulcerative gastritis.
* Documented history of congestive heart failure, angina pectoris poorly controlled by medication; ECG-confirmed transmural myocardial infarction; uncontrolled hypertension; clinically significant valvular disease; high-risk or uncontrolled arrhythmias.
* Severe systemic concurrent diseases, such as active infection or poorly controlled diabetic complications; coagulation disorders; bleeding tendency; or insufficient thrombolytic/anticoagulant therapy.
* Female participants with a positive serum pregnancy test or who are breastfeeding, or individuals of childbearing potential unwilling to use contraception during the study period.
* Active infection with HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), or positive HIV serology; or positive HBV DNA/HCV RNA.
* Allergy to any of the drugs used in this study.
* History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation).
* History of peripheral nervous system disease, significant psychiatric disorder, or central nervous system disease.
* Concurrent use of other anti-tumor drugs.
* Current participation in, or prior participation in, another clinical trial that could potentially impact the results of this study.