This trial is conducted in patients with resectable locally advanced esophageal squamous cell carcinoma. The investigators plan to enroll 46 patients with resectable locally advanced esophageal cancer in Tianjin cancer hospital. Patients will be treated with serplulimab, nimotuzumab plus concurrent chemoradiotherapy (41.4Gy/1.8Gy/23F) . Six to eight weeks after the completion of neoadjuvant chemoradiotherapy, patients who are considered operable by surgeons will undergo radical resection of esophageal cancer. Postoperative pathological assessment includes MPR rate, pCR rate, and pathological response grade, etc. This trial aims to explore the safety and efficacy of adding serplulimab and nimotuzumab to neoadjuvant chemoradiotherapy, with a focus on whether the combined treatment regimen can enhance the efficacy and safety of neoadjuvant chemoradiotherapy.

Inclusion Criteria:

• Sign an informed consent form.

• Age ≥ 18 years, ≤ 75 years, both genders are eligible.

• Patients with histologically confirmed clinical stage of locally advanced (cT1N2-3M0 or cT2-4aN0-3M0) thoracic esophageal squamous cell carcinoma (8th UICC-TNM staging).

• ECOG: 0-1.

• Expected to achieve R0 resection.

• No prior treatment for the primary esophageal tumor, including drug therapy, surgery, and radiotherapy.

• No suspicious metastatic lymph nodes in the neck as suggested by neck enhanced CT or neck ultrasound; no systemic metastasis on imaging studies.

• Measurable lesions according to RECIST 1.1 criteria.

• Important organ functions meet the following requirements:

  1. Absolute neutrophil count ≥ 1.5×10^9, platelets ≥ 80×10^9, hemoglobin ≥ 90g/L;
  2. Total bilirubin level ≤ 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN (for patients with liver metastasis, AST and ALT levels ≤ 5 times ULN);
  3. Serum creatinine ≤ 1.5 times ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula);
  4. Serum albumin ≥ 28g/L;
  5. Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%);
  6. Pulmonary function: FEV1/FVC ≥ 70%, FEV1 ≥ 50% of normal value, DLCO (diffusing capacity of the lung for carbon monoxide) measured value to predicted value percentage > 80%.

• Women of childbearing age must agree to use contraception (such as intrauterine device, contraceptive pills, or condoms) during the study and for 6 months after the study ends; negative serum or urine pregnancy test within 7 days before study enrollment, and must be non-lactating patients; men must agree to use contraception during the study and for 6 months after the study ends.

• Must understand and sign the informed consent form.

Exclusion Criteria:

• Within the past six months, received EGFR monoclonal antibodies or EGFR-TKIs.
• Participated in other interventional clinical trials within 30 days prior to screening.
• Have severe comorbidities, such as heart failure, high-risk uncontrollable arrhythmias, severe myocardial infarction, refractory hypertension, renal failure (CKD stage 4 or higher), thyroid dysfunction, mental disorders, diabetes, severe chronic diarrhea (more than 7 bowel movements per day), etc., and those deemed unsuitable for this clinical study by the investigator.
• Patients with brain metastases with symptoms or symptom control for less than 3 months.
• History of other malignancies (except for cured in situ cervical cancer or skin basal cell carcinoma, and other malignancies cured for more than 5 years).
• Presence of active infection or active infectious disease.
• Multifocal esophageal malignant tumors or presence of esophageal fistula or perforation signs.
• Imaging shows tumor invasion of important blood vessels, or the investigator determines that the tumor is highly likely to invade important blood vessels during the subsequent study period, leading to fatal major bleeding.
• Allergy to the drugs used in this protocol or their components.
• According to the Common Terminology Criteria for Adverse Events (NCI CTCAE V5.0), peripheral neuropathy or hearing loss of grade ≥2.
• Pregnant or breastfeeding women.
• Those with a history of psychiatric drug abuse and unable to quit, or patients with mental disorders.
• Those deemed unsuitable for this study by the investigator.
• Those unwilling to participate in this study or unable to sign the informed consent form.