Pembrolizumab in Combination with Flutamide Treatment for Recurrence / Metastasis HNSCC

Inclusion criteria

• Age ≥ 18 years old, ≤ 85 years old
• 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 A without distant metastasis according to AJCC staging (8th editon), including squamous cell carcinoma of oropharyngeal (P16-), oral cavity, hypopharyngeal and larynx
• Measurable primary lesions per RECIST 1.1 criteria
• Treatment-naive patients without any previous disease-related therapy (except for diagnostic biopsies on primary lesions)
• ECOG performance status of 0 or 1
• Unresectable primary, recurrent, and / or metastatic HNSCC
• No active autoimmune disease
• No concurrent malignancy
• Life expectancy is estimated to be over 3 months
• Have sufficient tumour tissue samples available for CPS PD-L1 immunohistochemical examination (22C3 DAKO)
• 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 bleeding tendency within 7 days
• ALT,AST and ALP ≤ 2.5 × upper limit of normal (ULN); Serum bilirubin ≤ 1.5 × ULN, for patients with known Gilbert disease, serum bilirubin ≤ 3 x ULN
• Serum creatinine ≤1.5 or creatinine clearance>50 mL/min
• HPV status determined by p16 IHC, in situ hybridization, or by polymerase chain reaction-based assays
• Able to understand this study, patient and (or) legal representative voluntarily agree to participate in this trial and sign informed consent

Exclusion criteria

• Patients who are suitable for local treatment and have the intention of local treatment
• Received systemic treatment with Chinese patent drugs with anti-tumor indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukin) within 2 weeks before the first administration
• Patients with tumor progression after previous treatment with flutamide analogues (antiandrogens)
• Other malignant tumors occurred within 5 years or suffered from at the same time in the current period, except for cured non melanoma skin cancer or other tumors / cancers that have undergone radical treatment and have no signs of disease for at least 5 years;
• According to the criteria of common adverse event terminology (NCI ctcaev5.0), there was peripheral neuropathy ≥ grade 2
• With known active central nervous system metastasis (CNS) and / or cancerous meningitis
• Subjects who did not recover from any acute effects of previous surgery, chemotherapy or radiotherapy, i.e. did not fall to grade ≤ 1 (NCI ctcaev5.0) (excluding hair loss). Chronic late toxicity from previous radiotherapy and / or surgery is allowed if nutritional status is stable
• Any component of the study drug or preparation has led to severe allergic reactions, including known severe allergic reactions to flutamide and (NCI ctcaev5.0 ≥ grade 3)
• Have received anti-tumor drug treatment (such as chemotherapy, hormone therapy, immunotherapy, antibody therapy, radiotherapy, etc.) within 4 weeks or 4 weeks before the first administration, except for palliative radiotherapy for bone to reduce pain
• Major surgery within 4 weeks before the first dose or expected during this study
• Immunosuppressive drugs were required 2 weeks or within 2 weeks before the first dose or during the study
• Subjects who are known to have active, or have a history of autoimmune disease that may recur
• Subjects with known history of interstitial lung disease, non infectious pneumonia, or high suspicion of interstitial lung disease
• Hepatitis B or C virological examination meets any of the following requirements at the time of screening:

• HBsAg is positive, and the titer of hepatitis B virus deoxyribonucleic acid (HBV DNA) in peripheral blood is ≥ 104 copies /ml or ≥ 2000 iu/ml;
• HCV antibody was positive, and HCV-RNA was higher than the detection limit of the analytical method;
• Within 2 weeks or 2 weeks before the first administration, the subject had active infection or uncontrollable infection requiring systemic treatment (except simple urinary tract infection or upper respiratory tract infection)
• Serous cavity effusion with clinical symptoms requiring clinical intervention or stabilization time less than 4 weeks
• Diabetes mellitus (fasting blood glucose ≥ 10mmol/l) or hypertension (systolic blood pressure ≥ 160mmhg and / or diastolic blood pressure ≥ 100mmhg) with severe medical diseases, such as grade III or above cardiac dysfunction (New York Heart Association [nyha]), ischemic heart disease (such as myocardial infarction or angina pectoris) and other cardiovascular diseases, or a history of myocardial infarction within 3 months before the first administration, and still poorly controlled after drug treatment (fasting blood glucose ≥ 10mmol/l) or poorly controlled hypertension (systolic blood pressure ≥ 160mmhg and / or diastolic blood pressure ≥ 100mmhg)
• Medical or psychiatric history or history of laboratory abnormalities that may interfere with the interpretation of the results
• Subjects are currently enrolled in the study of other investigational devices or investigational drugs, or are less than or equal to 4 weeks away from the discontinuation of other investigational drugs or investigational devices
• Subjects were known to have alcohol or drug addiction
• Subjects have other conditions that may affect their compliance with the protocol and evaluation of research indicators, and are not suitable to participate in the study