Study of Pembrolizumab Combined with Chemotherapy in the First Line Therapy for R/M HNSCC in China

Inclusion Criteria:

1. Voluntarily sign written informed consent before screening;

2. Age 18~75 years old;

3. ECOG physical status score 0-1 points;

4. Head squamous cell carcinoma (HNSCC) diagnosed by histology or cytology, the primarysite is oral cavity, oral cavity Throat, lower throat or throat;

5. Recurrent and/or metastatic HNSCC without indications for local radical treatment;

6. According to the evaluation criteria for the efficacy of solid tumors (RECISTversion 1.1), there is at least one measurable lesion, right For lesions that havereceived radiotherapy in the past, only if there is clear disease progression 3months after the end of radiotherapy, can it be Was selected as the target lesion;

7. There are a large number of tumor tissue samples for PD-L1 immunohistochemicaldetection;

8. The expected survival period exceeds 3 months;

9. The main organs function normally, that is, they meet the following standards: I. Blood routine (not receiving blood transfusion 14 months before screeningexamination, erythropoietin (EPO), granulocyte set Fall stimulating factor (G-CSF)or granulocyte-macrophage colony stimulating factor (GM-CSF) treatment): neutralGranulocyte ≥1.5×l09

• L, platelets ≥100×109

• L, hemoglobin≥90g/L; ii. Liver function: alanine aminotransferase (ALT) andaspartate aminotransferase (AST), ALT and AST ≤ 3 for those without livermetastasis ×ULN, ALT and AST for liver metastases≤5×ULN; total bilirubin (TBIL)≤1.5×ULN (Gilbert Syndrome patients, ≤3×ULN); iii. Renal function: Serumcreatinine (Cr)≤1.5×ULN or tendon clearance (Ccr)≥50ml/min (connect Residuestreated with carboplatin) or ≥60ml/min (residuals treated with cisplatin); iv.Coagulation function: activated partial thromboplastin time (APTT),international normalized ratio (INR), thrombin Original time (PT)≤1.5×ULN; v.Heart echocardiogram: left ventricular ejection fraction (LVEF) ≥50%;

10. Women should agree to use contraceptive measures (such as intrauterine birthcontrol) during the study period and within 6 months after the study ends.

Device [IUD], contraceptive pill or condom); 7 diabetes blood pregnancy test was negative before study enrollment, and it must be non-Breastfeeding patients; males should agree to use contraceptive measures during the study period and within 6 months after the end of the study period patient.

Exclusion Criteria:

1. Patients who are suitable for local treatment and are willing to local treatment;

2. Have received systemic chemotherapy, but does not include treatment for locallyadvanced disease as a part of multimodal treatment Chemotherapy (the end of thistreatment must be more than 6 months after the first trial medication); Note:Multimodal therapy includes induction chemotherapy, concurrent radiotherapy andchemotherapy and adjuvant chemotherapy.

3. Locally advanced head and neck squamous cell carcinoma multimodal treatment iscompleted within 6 months of disease progression;

4. Have received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4antibodies or targeting effects in the past Any other antibody or drug immunotherapyin T cell co-stimulation or immune checkpoint pathway;

5. Other malignant tumors have occurred within 5 years or at the same time during thecurrent period, except for cured cervical carcinoma in situ, non- Skin cancer ofmelanoma or other tumors/cancers that have undergone radical treatment and have nosigns of disease for at least 5 years;

6. Received cetuximab treatment within 6 months before the first administration;

7. According to the standard of common adverse event term (NCI CTCAEv5.0), peripheralneuropathy has been ≥2 grade;

8. With known active central nervous system metastasis (CNS) and/or cancerousmeningitis: previous treatment Subjects with brain metastases treated for treatmentcan participate in the study, provided that they are clinically stable for at least 2 weeks and there are no new or enlarged brains. Evidence was transferred, and steroids were discontinued 14 days before study drugadministration. The stable brain metastasis in this definition should be inDetermine before the first administration of the study drug. Subjects withasymptomatic brain metastases (ie no neurological symptoms, no need Corticosteroids,and no lesions> 1.5cm) can participate, but the brain needs to be regularlyperformed as a disease site Film degree exam;

9. Did not recover from any acute effects of previous surgery, chemotherapy orradiotherapy, that is, did not fall to ≤1 grade (NCI CTCAEv5.0) subjects (except forhair loss). If the nutritional status is stable, allow previous radiotherapy and/orsurgery Chronic late toxicity (pharyngeal/larynx toxicity, ie dry mouth, abnormalspeech, swallowing, etc.);

10. Any component of the studied drug or preparation has caused severe allergicreactions, including known Severe allergic reaction to Longan antibody (NCICTCAEv5.0≥3);

11. Have received anti-tumor drug treatment (such as chemotherapy, hormone therapy,immune Disease treatment, antibody treatment, radiotherapy, etc.), except forpalliative radiotherapy for bones to relieve pain;

12. Chinese herbal medicine or Chinese patent medicine receiving anti-tumor treatment ≤1week before the first administration;

13. Have received major surgery within 4 weeks before the first administration or areexpected to undergo major surgery during the study period;

14. Immunosuppressive drugs need to be used 2 weeks before the first administration orwithin 2 weeks or during the study period. The following conditions are excluded:

15. Intranasal, inhaled, topical steroid or topical steroid injection (such asintra-articular injection);

16. Physiological dose of systemic corticosteroids (≤10mg/day prednisone orequivalent dose);

17. Short-term (≤7 days) use of steroids to prevent or treat non-autoimmuneallergic diseases;

18. Subjects who are known to have active or have a history of autoimmune diseases thatare likely to relapse (such as: Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,autoimmune thyroid disease, multiple Sexual sclerosis, vasculitis, glomerulitis,etc.), or high risk (such as receiving an organ transplant and requiringimmunotherapy) Of patients. However, the following patients are allowed to join thegroup: patients with type I diabetes who are in stable condition after using a fixeddose of insulin Those; autoimmune hypothyroidism requiring only hormone replacementtherapy; no need for systemic therapy Skin diseases (such as eczema, skin rashesthat account for less than 10% of the body surface, psoriasis withoutophthalmological symptoms, etc.);

19. Subjects with known history of interstitial lung disease, history of non-infectiouspneumonia, or high suspicion of interstitial lung disease Those who have previouslyhad drug-induced or radiation non-infectious pneumonia but asymptomatic subjects areallowed to enter the group;

20. A history of human immunodeficiency virus infection (positive HIV test), or otheracquired or congenital Immunodeficiency disease, or history of organtransplantation, or history of stem cell transplantation;

21. The hepatitis B or C virological examination at the time of screening meets any ofthe following:

22. HBsAg positive, and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) titer ≥104 Copy number/ml or ≥2000 IU/ml;

23. HCV antibody is positive, and HCV-RNA is higher than the detection limit of theanalysis method;

24. Within 2 weeks or 2 weeks before the first administration, the subject has an activeinfection that requires systemic treatment or is uncontrollable Infection (exceptfor simple urinary tract infection or upper respiratory tract infection);

25. Live virus vaccine was vaccinated within 4 weeks before the first dose. Allowsvaccination against seasonal influenza that does not contain live viruses seedling;

26. Serous effusions (such as pleural effusions and pleural effusions) with clinicalsymptoms that require clinical intervention or stable time less than 4 weeksascites);

27. Known to be accompanied by serious medical diseases, such as heart functionabnormalities of grade III and above (New York Heart Association [NYHA]),cardiovascular diseases such as ischemic heart disease (such as myocardialinfarction or angina pectoris), or before the first administration 3 A history ofmyocardial infarction within months, and poorly controlled diabetes (fasting bloodglucose ≥ 10mmol/L) or poorly controlled hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg);

28. Medical or psychiatric history or laboratory abnormal history that may interferewith the interpretation of results;

29. The subject is currently enrolled in other research equipment or research drugresearch, or is away from other research drugs Or the study device is out of use forless than or equal to 4 weeks;

30. The subject is known to be addicted to alcohol or drugs;

31. The researcher believes that the subjects have other conditions that may affecttheir compliance with the protocol and the evaluation of research indicators.

Circumstances, subjects who are not suitable to participate in the study.