Neoadjuvant Docetaxel, Cisplatin, and Dual Immunotherapy for Sinonasal Carcinoma (PANDA)

Inclusion Criteria:

• 1. Disease Status: Newly diagnosed, pathologically confirmed locally advanced (AJCC 8th edition Stage III-IVA) sinonasal carcinoma (SNC).

  2. Suitable for radical comprehensive treatment, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.

  3. 18 to 75 years old. 4. Defined by the following laboratory test results obtained within 7 days prior to enrollment: Hematology (without blood transfusion or hematopoietic growth factor therapy within 14 days prior to testing): White blood cell (WBC) count ≥ 4.0 × 10^9/L; Absolute neutrophil count (ANC) ≥ 2.0 × 10^9/L; Platelet (PLT) count ≥ 100 × 10^9/L.

  5. Hepatic function: Total bilirubin < 1.5 × upper limit of normal (ULN) (patients with known Gilbert's disease and serum bilirubin level ≤ 3 × ULN are eligible); Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase < 1.5 × ULN. For patients positive for hepatitis B surface antigen (HBsAg), HBV-DNA must be ≤ 1000 IU/mL, and prophylactic antiviral therapy is required during the study.

  6. Renal function: Serum creatinine < 1.5 × ULN, or creatinine clearance ≥ 60 mL/min as calculated by the Cockcroft-Gault formula.

  7. Coagulation: Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN. Patients receiving stable doses of anticoagulant therapy (e.g., low molecular weight heparin or warfarin) with an INR within the expected therapeutic range are eligible.

  8. Thyroid function: Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels will be evaluated, and patients with normal T3 and T4 levels are eligible.

  9. Contraception: Women of childbearing potential must agree to use highly effective contraceptive measures (e.g., intrauterine device, contraceptive pills, or condoms) during the treatment period and for at least 3 months after the last dose. They must have a negative serum or urine pregnancy test within 7 days prior to enrollment and must not be lactating. Male patients must agree to use highly effective contraceptive measures during the study period and for at least 3 months after the last dose.

  10. Informed Consent: Voluntary participation with written informed consent signed.

Exclusion Criteria:

• 1. History of other malignancies within the past 5 years, except for curatively treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma.

  2. Presence of residual measurable lesions or new tumor/metastasis according to RECIST 1.1 criteria, or deemed inoperable by a head and neck surgeon.

  3. History of severe hypersensitivity reactions to other monoclonal antibodies or any components of the PD-1 inhibitors.

  4. Prior and Concomitant Therapies: Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (or any other antibody targeting T-cell costimulation or checkpoint pathways).

  5. Use of high-dose glucocorticoids or traditional Chinese medicine with anti-tumor properties within 4 weeks prior to the first dose of the study drug.

  6. Prior vaccination with an anti-tumor vaccine, or receipt of a live vaccine within 4 weeks prior to the first dose of the study drug.

  7. Receipt of any investigational drug within 4 weeks prior to the first dose of the study drug.

  8. Presence of comorbidities requiring long-term immunosuppressive therapy, or requiring systemic or local administration of corticosteroids at immunosuppressive doses prior to enrollment.

  9. Concurrent Trials: Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up phase of an interventional study.

  10. Recent Medical Events: Major surgery or severe trauma within 4 weeks prior to the first dose of the study drug.

  11. Organ Transplantation: History of organ transplantation. 12. Autoimmune Diseases: Known or suspected active autoimmune disease. 13. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).

  14. Concurrent positive HBsAg and positive HBV DNA copy number (quantitative detection ≥ 1000 cps/mL). Positive blood screening for chronic hepatitis C (HCV antibody positive). Concurrent HBV and HCV co-infection. (Note: Patients with normal liver function who have been on oral antiviral therapy for more than one week may be eligible).

  15. Failure to meet relevant laboratory criteria within 7 days prior to enrollment; abnormal coagulation function (PT > 16s, APTT > 53s, TT > 21s, Fib < 1.5 g/L), bleeding tendency, or undergoing active thrombolytic or anticoagulant therapy.

Significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function. History of dementia or seizures.

16. Severe Infections: Severe infection (CTCAE > Grade 2) within 4 weeks prior to the first dose of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; baseline chest imaging indicating active pulmonary inflammation; presence of signs and symptoms of infection within 2 weeks prior to the first dose of the study drug, or requiring oral or intravenous antibiotic therapy (excluding prophylactic use of antibiotics).

17. Pregnancy and Lactation: Pregnant or lactating women; women of childbearing potential who refuse to use effective contraceptive measures.

18. Compliance and Legal Capacity: Refusal or inability to sign the informed consent form; presence of personality or psychiatric disorders; lack of or limited civil capacity.

19. Other: Presence of any other treatment contraindications deemed inappropriate by the investigator.