Study of Pembrolizumab Combined With Anlotinib in the First Line Therapy for R/M HNSCC With CPS≥1

Inclusion Criteria:

• 1. Voluntarily sign written informed consent before screening; 2) Age ≥18 years old;

3. ECOG physical status score 0-1; 4) Histologically or cytologically confirmedsquamous cell carcinoma of the head and neck (HNSCC) with primary site of oral cavity,oropharynx, hypopharynx or larynx; 5) Recurrent and/or metastatic HNSCC withoutindications of local radical treatment; 6) According to the efficacy evaluationcriteria for solid tumors (RECIST version 1.1), at least one measurable lesion can beselected as the target lesion after receiving previous radiotherapy only if there hasbeen definite disease progression 3 months after the end of radiotherapy; 7)Sufficient tumor tissue samples for PD-L1 immunohistochemical detection; 8) Expectedsurvival of more than 3 months; 9) The main organs function normally, that is, theymeet the following criteria: I. Blood routine (no blood transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophagecolony-stimulating factor (GM-CSF) treatment within 14 days before screeningexamination) : neutrophils ≥1.5× L09 /L, platelets ≥100×109/L, hemoglobin ≥90g/L; II.Liver function: ALT and AST, ALT and AST≤3×ULN in patients without liver metastasis,ALT and AST≤5×ULN in patients with liver metastasis;Total bilirubin (TBil) ≤1.5×ULN (Gilbert syndrome patients, ≤3 ×ULN); Iii. Renal function: Serum creatinine (CR) ≤1.5×ULN or creatinine clearance (CCR) ≥50ml/ min (subjects receiving carboplatin) or ≥60ml/ min (subjects receiving cisplatin); IV. Coagulation function: APTT, INR, PT ≤1.5×ULN; V. Echocardiography: left ventricular ejection fraction (LVEF) ≥50%; 10)Women should agree to use contraceptives (such as intrauterine devices [IUDs],contraceptives or condoms) during the study period and for 6 months after the end ofthe study;Negative blood pregnancy test within 7 days prior to study enrolment andmust be non-lactating;Men should agree to use contraception during the study periodand within 6 months after the end of the study period.

Exclusion Criteria:

• 1. The patient had necrotic lesions and was judged by the investigator to be at riskof massive bleeding; 2) A history of hypersensitivity to amlotinib or pabrizumab orany excipients; 3) Previous use of antiangiogenic drugs (such as amlotinib, apatinib,bevacizumab, Endox, etc.); 4) The patient is using (or cannot be discontinued within 1week prior to the first dosing of the study treatment) a Chinese herbal medicineindicated for antitumor use; 5) poorly controlled pleural effusion, pericardialeffusion or ascites requiring frequent drainage;Patients with indwelling catheters (such as the Pleurx ® catheter) are allowed to participate; 6) At the beginning ofstudy treatment, there was still an uncured toxic reaction from previous treatment andCTCAE 5.0 was higher than level 1 (except for alopecia); 7) Spinal cord compression orsymptomatic untreated brain or spinal cord metastases (except asymptomatic, stablecondition, and no need for steroid therapy for 4 weeks prior to study treatment); 8)poorly controlled tumor-related pain.Patients who require analgesics must receive asteady dose before entering the study.Symptomatic lesions suitable for palliativeradiotherapy (e.g., bone metastases or metastases leading to nerve damage) should betreated before enrolment.Prior to enrolment, local-regional treatment of asymptomaticmetastatic lesions with further growth that may result in functional deficits orintractable pain (e.g., epidural metastases currently not associated with spinal cordcompression) should be considered, if appropriate.

9. Hepatitis B, hepatitis C or human immunodeficiency virus (HIV antibodypositive).Patients with positive hepatitis B antibodies were only eligible toparticipate in the study if they had HBV DNA ˂2000cps/ml.Patients with hepatitis Cantibody positive were eligible to participate in the study only if polymerase chainreaction showed HCV RNA negative; 10) Randomization of malignancies other thanadvanced head and neck squamous cell carcinoma with negligible risk of metastasis ordeath and expected radical outcome after treatment within the first 5 years (e.g.,Adequately treated carcinoma in situ of the cervix, basal or squamous cell skincancer, localized prostate cancer for radical treatment, and ductal carcinoma in situfor radical surgery); 11) Had major surgery other than a diagnosis of advanced headand neck squamous cell carcinoma within 28 days prior to randomization or was expectedto require major surgery during the study period; 12) patients who have had previousbone marrow transplantation or previous solid organ transplantation; 13) Any livevaccine (for example, vaccines against infectious diseases, such as influenza,varicella, etc.) was given within the first 4 weeks (28 days) of randomization; 14)any factors that may affect the patient's oral administration, such as inability toswallow, post-gastrointestinal resection, chronic diarrhea, and intestinalobstruction; 15) Meets any of the following cardiac criteria: mean corrected QTinterval (QTc) from an electrocardiogram (ECG) in the resting state;470 msec (for thefirst anomaly, the test was retest once within 48 h, calculated based on the averageresult of two times).A variety of clinically significant cardiac rhythm, conduction,and resting ECG abnormalities, such as complete left bundle branch block, degree III,degree II, PR interval >250 msec.Various factors that may increase the risk ofprolonged QTC or arrhythmic events, such as coronary heart disease, heart failure,hypokalemia, congenital long QT syndrome, a family history of first-degree relativewith long QT syndrome or sudden unexplained death under age 40, and being on any knownmedication for prolonged QT; 16) Patients with any severe and/or uncontrolled disease,including but not limited to: patients with poor blood pressure control (systolic > 150 mmHg, diastolic > 100 mmHg);Suffer from myocardial ischemia or myocardialinfarction, arrhythmias (including QTc ≥440ms) and congestive heart failure (New YorkHeart Association (NYHA) grade) of grade I or above;Active or uncontrolled severeinfection (≥CTC AE grade 2 infection);Cirrhosis, decompensated liver disease;Renalfailure requires hemodialysis or peritoneal dialysis;Poor diabetes control (fastingblood glucose (FBG) > 10mmol/L);Routine urine indicated urinary protein ≥++, andconfirmed 24-hour urinary protein quantitative > 1.0 g; 17) Patients with epilepticseizures requiring treatment, with a history of psychotropic substance abuse andunable to quit or with mental disorders; 18) Previous history of interstitial lungdisease, drug-induced interstitial lung disease, radiation pneumonia requiring steroidtreatment, and clinically evidenced active interstitial lung disease; 19) thromboticor embolic venous or arterial events, such as cerebrovascular accidents, includingtransient ischemic attack, arterial thrombosis, deep vein thrombosis and pulmonaryembolism, occurred within 6 months before enrollment;Has a history of hemorrhagicdisease or abnormal blood clotting.
10. Lactating female patients.