This study is a single arm phase ll trial including 30 patients with T2N2-3M0、T3-4N0-3M0 (lll-V) head and neck squamous cell carcinoma (HNSCC) eligible forresection, who receive neo-adjvuant Cadonilimab combined with cisplatin and Nab.paclitaxel.This proposed study will evaluate the efficacy and safety of preoperativeadministration of Cadonilimab combined with chemotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC) who are about to undergo surgery.

In this study, eligible subject will be enrolled into study arm to accept study treatment objective response rate will be the primary outcome measures.

Inclusion Criteria:

1. Newly diagnosed primary head and neck squamous cell carcinoma confirmed by histology and/or cytology (excluding diagnostic therapy).

2. Clinical stage: T2N2-3M0, T3-4N0-3M0 (III-IV) (AJCC 8th edition staging).

3. Age: 18 to 70 years.

4. PS score (see Appendix Table 1; performance status score of 0 or 1).

5. Patients evaluated by a head and neck oncologist as resectable with no distant metastases.

6. Patients with at least one measurable lesion according to RECIST version 1.1 criteria.

7. Patients' toxicities assessed according to CTCAE version 4.03 criteria.

8. Patients with normal organ function (heart, brain, lungs, kidneys) and suitable for surgery:

   1. Hematology: White blood cells ≥ 4000/μL, neutrophils ≥ 2,000/μL, hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL;
   2. Liver function: Bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with known Gilbert's disease and serum bilirubin levels ≤ 3 times ULN can be included), AST and ALT ≤ 3 times ULN, alkaline phosphatase ≤ 3 times ULN; albumin ≥ 3 g/dL;
   3. Renal function: Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min according to Cockcroft-Gault formula.

9. Consent to provide archived tumor tissue samples or undergo biopsy for collection of tumor lesion tissue (at least 3 unstained FFPE pathological slides, if deemed insufficient for PD-L1 IHC testing by the central laboratory, an additional 3 unstained FFPE pathological slides should be provided) to be sent to the central laboratory for PD-L1 immunohistochemistry (IHC) testing (preferably using recently obtained tumor tissue samples). Tumor lesions planned for biopsy should not be used for assessing target lesions of the disease unless no other suitable lesions for biopsy are available. Patients have signed an informed consent form, are willing and able to comply with the study's visit, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. History of severe hypersensitivity reactions to components of other monoclonal antibodies, CTLA4, or PD-1 antibodies.
2. Patients with known or suspected autoimmune diseases, including dementia and epileptic seizures.
3. Recurrence, distant metastasis, or the inability to undergo surgery as assessed by a head and neck physician.
4. Abnormal coagulation function: (PT > 16s, APTT > 53s, TT > 21s, Fib < 1.5g/L), bleeding tendency, or currently on anticoagulant or thrombolytic therapy.
5. Severe heart disease, pulmonary dysfunction, patients with heart or lung function below Grade 3 (including Grade 3).
6. Laboratory values not meeting relevant criteria within 7 days prior to enrollment.
7. Previous use of anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, or anti-CTLA-4 antibodies (or any other antibodies targeting T cell co-stimulation or checkpoint pathways).
8. Pre-existing conditions requiring long-term use of immunosuppressive drugs or a need for systemic or local use of corticosteroids at immunosuppressive doses prior to enrollment.
9. HIV-positive individuals; HBsAg-positive individuals with positive HBV DNA copy number (quantitative test ≥ 1000 cps/ml); positive chronic hepatitis C blood screening (HCV antibody positive).
10. Traditional herbal medicine used for anti-tumor purposes within 4 weeks before randomization.
11. Active or prior history of documented inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea).
12. Women of childbearing potential with a positive pregnancy test and breastfeeding women.
13. Known active pulmonary tuberculosis (TB). Subjects suspected of having active TB need clinical evaluation for exclusion.
14. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
15. Severe infection occurring within 4 weeks before the first administration, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia.
16. Subjects planning major surgery within 30 days after the first dose of AK104 in combination with platinum-containing dual-agent therapy (as determined by the investigator), or not yet fully recovered from prior surgery. Local surgical procedures (such as placement of a systemic port and prostate biopsy) are allowed provided that the surgery is completed at least 24 hours before the first dose of the study treatment.