Pembrolizumab in Combination With Low-dose PFas Neoadjuvant Treatment for Locally Advanced HNSCC

Inclusion Criteria:

1. Age ≥ 18 years old, ≤ 85 years old
2. Histologically or cytologically proven squamous cell carcinoma of the head and neck;Patients diagnosed with head and neck squamous cell carcinoma with stage III and IV Awithout distant metastasis according to AJCC staging (8th editon), including squamouscell carcinoma of oropharyngeal (P16-), oral cavity, hypopharyngeal and larynx
3. Measurable primary lesions per RECIST 1.1 criteria
4. Treatment-naive patients without any previous disease-related therapy (except fordiagnostic biopsies on primary lesions)
5. ECOG performance status of 0 or 1
6. Selective standard surgery+ standard adjuvant chemo-radiotherapy/radiotherapy asjudged by the investigator
7. No active autoimmune disease
8. No concurrent malignancy
9. Life expectancy is estimated to be over 3 months
10. Have sufficient tumour tissue samples available for CPS PD-L1 immunohistochemicalexamination (22C3 DAKO)
11. No abvious signs of hematological disorders, ANC≥1.5×109 /L, platelets ≥100×109 /L,Hb≥ 90 g/L,WBC ≥3.0×109 /L before enrollment, no blood transfusion and bleedingtendency within 7 days
12. ALT,AST and ALP ≤ 2.5 × upper limit of normal (ULN); Serum bilirubin ≤ 1.5 × ULN, forpatients with known Gilbert disease, serum bilirubin ≤ 3 x ULN
13. Serum creatinine ≤1.5 or creatinine clearance>50 mL/min
14. HPV status determined by p16 IHC, in situ hybridization, or by polymerase chainreaction-based assays
15. Able to understand this study, patient and (or) legal representative voluntarily agreeto participate in this trial and sign informed consent

Exclusion Criteria:

1. Multiple organs failure
2. HPV p16 positive oropharyngeal cancer
3. Patients with local advanced head and neck squamous cell carcinoma stage T4B and/or N3
4. Patients with distant metastasis
5. Uncontrolled serious diseases that, as assessed by investigator, may affect thesubject's treatment with the study protocol, such as serious heart disease,cerebrovascular disease, uncontrolled diabetes mellitus, uncontrolled hypertension,uncontrolled infection, active peptic ulcer, etc.
6. Diagnosis of dementia, altered mental status or any mental illness that would preventsubjects understanding or giving informed consent or completing questionnaires
7. Subjects with ≥ Grade 2 peripheral neuropathy according to CTCAE V5.0
8. Subjects with ≥ Grade 2 hearing impairment according to CTCAE V5.0
9. History of allergy or hypersensitivity to any of the therapeutic ingredients
10. Diagnosis of malignancy within 5 years prior to screening, including HNSCC (other thancurrent HNSCC) and other malignancies; Eligibility is achieved if all of the followingcriteria are met: malignancies received curative therapy, such as adequately treatedcervical carcinoma in situ, non-melanoma cutaneum carcinoma, localized prostate cancerafter radical operation, breast ductal carcinoma in situ after radical operation;There was also no evidence of recurrence or metastasis based on imaging and tumormarkers
11. Known history of human immunodeficiency virus (HIV) or acquired immunodeficiencysyndrome (AIDS)
12. Patients diagnosed with nasopharyngeal carcinoma or squamous cell carcinoma whoselesions are located in parts other than the oral cavity, oropharynx, larynx andhypopharynx (such as sinuses, paranasal sinuses and unknown primary site)
13. Participated in other clinical intervention trials or received other investigationaltherapies within 30 days prior to screening
14. Patients received systemic corticosteroids (prednisone equivalent dose>10mg/day) orother immunosuppressive drugs within 14 days prior to randomization. If there is noactive autoimmune disease, inhaled or topical steroid hormones and adrenal hormonereplacement therapy with prednisone equivalent doses>10mg per day are permitted
15. Pregnant or breastfeeding; Subjects of childbearing age refuse to accept contraceptivemeasures
16. Patients unfit for study as assessed by the investigator
17. Received systemic antibiotics within 1 weeks prior to first dose of study therapy oractive infection requiring treatment
18. Known history of HBV infection (defined as HBsAg positive) or active HCV infection (defined as HCV RNA detected)
19. Has received live vaccine during study or within 30 days prior to first dose of studytherapy