Paclitaxel Polymeric Micelles and Cisplatin Plus Sintilimab as Neoadjuvant Therapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

• Paclitaxel polymer micelles for injection and cisplatin combined with sintilimab (Drug): 1. Sindilimab : 200 mg, Q3W, intravenous infusion, D1 ; 2. Paclitaxel polymeric micelles : 300 mg/m2 ; q3W, intravenous infusion, D1 ; 3. Cisplatin : 75 mg/m2 ; q3W ; intravenous infusion, D1 ;

Primary outcomes

• Pathological Complete Response (pCR) rate [Assessed via surgical pathology (4-6 weeks post-neoadjuvant therapy)]: Pathological Complete Response (pCR) rate: Proportion of patients with no residual invasive tumor in primary tumor bed and sampled lymph nodes (ypT0/Tis ypN0) after neoadjuvant therapy

Secondary outcomes

• Major Pathological Response (MPR) rate [Perioperative]
• R0 resection rate [Perioperative]
• Objective Response Rate (ORR) per RECIST v1.1 [Assessed at baseline and pre-surgery]
• Event-Free Survival (EFS) [Follow-up every 3 months for 2 years, then every 6 months up to 5 years]
• Overall Survival (OS) [Follow-up every 3 months for 2 years, then every 6 months up to 5 years]
• Safety: Incidence of adverse events (AEs), serious AEs (SAEs), and immune-related AEs (irAEs) [From initiation of treatment to 30 days post-last dose (or 90 days for SAEs)]

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Written informed consent was signed before the implementation of any test-related procedures ;
2. Age 18-75 years ;
3. Esophageal squamous cell carcinoma confirmed by histopathology ;
4. Resectable thoracic cT1b-2N1-3M0 or cT2-3N0M0 ;
5. No anti-tumor treatment has been received ;
6. ECOG PS 0-1 ;
7. Expected survival ≥ 3 months ;
8. At least one measurable lesion per RECIST v1.1;
9. Adequate organ function (hematology, liver, kidney, coagulation, thyroid, myocardial enzymes) ;
10. For women of childbearing age, a negative urine or serum pregnancy test should be performed within three days prior to the first study drug administration ( day 1 of the first cycle ). If the urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is required. Women of non-fertility age were defined as at least 1 year after menopause, or had undergone surgical sterilization or hysterectomy ;
11. If there is a risk of conception, all subjects ( male or female ) are required to use contraception with an annual failure rate of less than 1 % throughout the treatment period up to 120 days after the last study drug administration ( or 180 days after the last study drug administration ).

Exclusion Criteria:

1. High risk of tracheoesophageal fistula or aortoesophageal fistula
2. Prior radiotherapy, chemotherapy, targeted therapy, or immunotherapy
3. Participation in another interventional clinical trial within 4 weeks before the first dose
4. History of other active malignancies (except cured low-risk tumors, adequately treated non-melanoma skin cancer, or carcinoma in situ)
5. Active uncontrolled hepatitis B/C infection
6. Uncontrolled systemic diseases (e.g., heart failure NYHA ≥II, interstitial lung disease, active autoimmune diseases requiring systemic immunosuppression)
7. Allergy to study drugs or excipients
8. Uncontrolled third-space effusion (e.g., pleural/pericardial effusion)
9. Pregnant or lactating women

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