Neoadjuvant Sacituzumab Tirumotecan Plus Toripalimab in Locally Advanced Esophageal Squamous Cell Carcinoma

Inclusion Criteria:

* Age \>=18 years at the time of informed consent, either sex.
* Histologically or cytologically confirmed locally advanced esophageal squamous cell carcinoma.
* Judged by imaging and esophagoscopy as resectable and requiring neoadjuvant therapy, with clinical stage cT1-2N+M0 or T3-4N0-3M0 (stage II-IVA).
* No prior antitumor therapy for esophageal squamous cell carcinoma.
* At least one measurable lesion per RECIST v1.1.
* ECOG performance status of 0 or 1 within 7 days before dosing.
* Adequate organ and bone marrow function (no transfusion, recombinant human thrombopoietin, or colony-stimulating factor within 2 weeks before the first dose):
* Hematology: NEUT# \>=1.5x10\^9/L; PLT \>=100x10\^9/L; hemoglobin \>=90 g/L.
* Hepatic: AST and ALT \<=2.5xULN (\<=5xULN for participants with baseline liver metastases); albumin \>=30 g/L; total bilirubin \<=1.5xULN.
* Renal: creatinine clearance \>=60 mL/min (Cockcroft-Gault formula).
* Coagulation: INR, APTT, and PT \<=1.5xULN.
* Normal thyroid function, defined as TSH within the normal range. If baseline TSH is outside the normal range, participants with total T3 (or FT3) and FT4 within the normal range are also eligible.
* Cardiac enzymes within the normal range (isolated laboratory abnormalities judged by the investigator as not clinically significant are allowed).
* Left ventricular ejection fraction \>=55%.
* Women of childbearing potential and men with partners of childbearing potential must agree to use effective medical contraception from informed consent until 6 months after the last dose.
* Participants voluntarily join the study, sign the informed consent form, and are able to comply with the scheduled visits and procedures.

Exclusion Criteria:

* Any prior antitumor therapy for the currently diagnosed esophageal squamous cell carcinoma.
* History of other malignancies within 5 years (except cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and carcinoma in situ of the cervix).
* Requirement for strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks before the first dose or during the study.
* Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or a history of corneal disease that interferes with or delays corneal healing.
* Any of the following cardiovascular or cerebrovascular diseases or risk factors:
* Myocardial infarction, unstable angina, acute or persistent myocardial ischemia, grade 3 or 4 heart failure (NYHA classification), symptomatic or poorly controlled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other severe cardiovascular or cerebrovascular diseases within 6 months before dosing.
* History of myocarditis, primary cardiomyopathy, or specific cardiomyopathy.
* Any deep vein thrombosis (participants stabilized with low molecular weight heparin or similar therapy for \>=2 weeks may be allowed), peripheral arterial thromboembolic event, pulmonary embolism, or other severe thromboembolic events within 3 months before dosing.
* Aortic aneurysm, aortic dissecting aneurysm, or other major vascular disease that may be life-threatening or requires surgery within 6 months before dosing.
* Uncontrolled systemic disease as judged by the investigator:
* Poorly controlled diabetes mellitus (two consecutive fasting glucose levels \>=9 mmol/L).
* Poorly controlled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg).
* Symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
* History of steroid-requiring (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis; current ILD or non-infectious pneumonitis; or suspected ILD or non-infectious pneumonitis that cannot be excluded by imaging at screening.
* Active autoimmune disease requiring systemic treatment within the past 2 years, including disease-modifying drugs, immunosuppressants, or systemic corticosteroids (\>10 mg/day prednisone or equivalent). Hormone replacement therapy such as thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency is not considered systemic treatment. Participants receiving systemic corticosteroids \>10 mg/day prednisone or other immunosuppressive drugs within 2 weeks before dosing.
* Known active pulmonary tuberculosis. Participants with suspected active pulmonary tuberculosis must undergo clinical evaluation to exclude it.
* Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
* Active hepatitis B (HBsAg positive with HBV-DNA \>=500 IU/mL or above the lower limit of detection, whichever is higher) or hepatitis C (HCV antibody positive with HCV-RNA above the lower limit of detection). Participants who are HBsAg positive are required to receive anti-hepatitis B viral therapy during the study.
* Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
* Known hypersensitivity to the study drugs or any of their components, or a history of severe hypersensitivity reactions to other biologics.
* Severe infection within 4 weeks before dosing, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks before dosing.
* Receipt of non-specific immunomodulatory therapy (including but not limited to interferon, IL-2) or Chinese patent medicines approved for antitumor indications within 2 weeks before dosing.
* Receipt of a live vaccine within 30 days before dosing, or planned receipt of a live vaccine during the study.
* Rapid deterioration during screening before dosing, such as a marked change in performance status.
* Pregnant or breastfeeding women.
* Local or systemic diseases caused by non-malignant conditions, or diseases or symptoms secondary to the tumor, that may lead to high medical risk and/or uncertainty in survival evaluation, such as leukemoid reaction or cachexia.
* Any condition that, in the investigator's judgment, interferes with the evaluation of the study drug, participant safety, or interpretation of study results, or any other condition that makes the participant unsuitable for this study.