Neoadjuvant therapy with adebrelimab, famitinib, and chemotherapy for resectable ESCC

Inclusion Criteria:

1. Signed written informed consent and voluntarily agrees to participate in the study.
2. Histologically or cytologically confirmed esophageal squamous cell carcinoma (ESCC).
3. Thoracic esophageal cancer evaluated by CT, MRI, or EUS, with clinical stage T1b-T2N+ or T3-T4a, any N (according to the AJCC 8th edition).
4. Expected to achieve R0 resection after neoadjuvant therapy.
5. Age between 18 and 75 years, male or female.
6. \*\*ECOG performance status of 0-1.
7. No prior anti-tumor therapy for esophageal cancer, including radiotherapy, chemotherapy, or surgery.
8. Planned to undergo surgical resection after completion of neoadjuvant therapy.
9. No contraindications to surgery.
10. Adequate organ function, defined as follows:

    a) Hematology (without the use of any blood components, hematopoietic growth factors, leukocyte or platelet stimulants, or anemia-correcting agents within 14 days before first study drug administration):

    \* Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L

    \* Platelet count ≥ 100 × 10⁹/L
    * Hemoglobin ≥ 90 g/L b) Serum biochemistry:
    * Total bilirubin ≤ 1.5 × ULN
    * ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN
    * Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min c) Coagulation:
    * INR ≤ 1.5 × ULN
    * APTT ≤ 1.5 × ULN
11. Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to first dosing and must agree to use effective contraception (such as intrauterine device, oral contraceptives, or condoms) during the study and for at least 3 months after the last dose.Male participants with partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study and for 3 months after the last dose.
12. Good compliance and willingness to adhere to study visits and follow-up requirements.

Exclusion Criteria:

1. Tumor invasion into adjacent vital structures of the esophageal lesion (e.g., major arteries or trachea).
2. Presence of supraclavicular lymph node metastasis.
3. Presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
4. Poor nutritional status with BMI \< 18.5 kg/m²; patients may be reconsidered for inclusion after nutritional support and investigator assessment.
5. Known hypersensitivity to monoclonal antibodies, adebrelimab, paclitaxel, cisplatin, or other platinum-containing agents.
6. Prior or current receipt of any of the following treatments:

   1. Any prior radiotherapy, chemotherapy, or other anti-tumor therapy for esophageal cancer;
   2. Use of immunosuppressive drugs or systemic corticosteroids for immunosuppressive purposes (prednisone \>10 mg/day or equivalent) within 2 weeks before the first dose of study drug. Inhaled or topical corticosteroids, or physiologic replacement doses (\>10 mg/day prednisone or equivalent) are permitted in the absence of active autoimmune disease;
   3. Receipt of a live attenuated vaccine within 4 weeks before the first dose of study drug;
   4. Major surgery or severe trauma within 4 weeks prior to the first dose of study drug.
7. Active autoimmune disease or history of autoimmune disease, including but not limited to interstitial pneumonitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism (patients with thyroid disorders controlled on hormone replacement may be eligible). Patients with psoriasis or childhood asthma/allergies that have resolved without intervention may be eligible, but those requiring bronchodilators are excluded.
8. History of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency disorders, organ transplantation, or allogeneic bone marrow transplantation.
9. Uncontrolled or clinically significant cardiac conditions, including but not limited to:

(1) Heart failure ≥ NYHA Class II; (2) Unstable angina; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias that are uncontrolled despite treatment.

10\. Severe infection (CTCAE grade \>2) within 4 weeks prior to first dosing, such as pneumonia requiring hospitalization, bacteremia, or other severe infections.

Patients with active pulmonary infection on baseline imaging, symptoms or signs of infection, or those requiring oral or intravenous antibiotics within 14 days prior to first dosing are excluded, except for prophylactic antibiotic use.

11\. Active tuberculosis (TB) infection confirmed by history or CT findings, history of active TB within 1 year before enrollment, or history of TB more than 1 year prior without adequate treatment.

12\. Tumor encasement of major blood vessels or presence of significant necrosis or cavitation on imaging that, in the investigator's judgment, would increase the risk of bleeding.

13\. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or ≥ 10⁴ copies/mL) or active hepatitis C infection (HCV antibody positive and HCV RNA above the lower limit of detection).

14\. History of another malignancy within 5 years prior to the first dose, except for malignancies with negligible risk of metastasis or death (e.g., adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix).

15\. Pregnant or breastfeeding women. 16. Any other condition that, in the investigator's judgment, may interfere with study participation or result in early withdrawal, including severe concomitant diseases (including psychiatric disorders) requiring treatment, alcohol or drug abuse, or social/familial factors that may affect compliance or safety.