A Clinical Trial of TQB2618 Injection Combined With Penpulimab Injection and Chemotherapy Versus Penpulimab Injection Combined With Chemotherapy in First-line Treatment of Relapsed/Metastatic Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

• The subjects voluntarily joined the study, signed the informed consent form, and hadgood compliance.
• Between the ages of 18-75 years (calculated based on the date of signing ICF); male orfemale; Eastern cooperative oncology group (ECOG) score 0-1; estimated survival time ≥ 3 months.
• No indications of local radical therapy for recurrence/metastasis head and necksquamous cell carcinoma.And histologically- or cytologically-confirmed head and necksquamous cell carcinoma ，Primary tumor locations of oropharynx, oral cavity,hypopharynx, or larynx.
• No systemic therapy for recurrent/metastatic lesions, but excluding systemic therapyfor locally advanced disease as a part of multimodal therapy (including inductiontherapy, systemic therapy in the same period of radiotherapy, and adjuvant therapy),and the completion time of treatment was more than 6 months from enrollment (accordingto the date of informed consent);
• At least one measurable lesion (based on RECIST1.1).
• The main organs function are normally, the following criteria are met:

1. hemoglobin (Hb) ≥90g/L (no blood transfusion and blood products within 14 days) ；absolute neutrophil count (ANC) ≥1.5×109/L； platelets (PLT) ≥90×109/L.
2. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); Alanineaminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. Ifaccompanied by liver metastases, ALT and AST ≤ 5×ULN; Serum creatinine (CR) ≤ 1.5×ULN or creatinine clearance (CCR) ≥ 60 ml/min.
3. Prothrombin time (PT), activated partial thromboplastin time (APTT),international normalized ratio (INR) ≤ 1.5×ULN (no anticoagulant therapy);Thyroid-stimulating hormone (TSH) ≤ ULN; If abnormalities should be examined, T3and T4 levels should be examined, and T3 and T4 levels are normal.
4. Cardiac ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%.

• Female participants of childbearing age should agree to use contraception (e.g., IUDs,pills, or condoms) during the study period and for 6 months after the end of thestudy; Have a negative serum pregnancy test within 7 days prior to study enrollmentand must be a non-lactating subject; Male participants should agree that contraceptionmust be used during the study period and for 6 months after the end of the studyperiod.

Exclusion Criteria:

• Comorbidity and medical history:

1. Have had or currently have other malignant tumors within 3 years. The followingtwo conditions can be enrolled: other malignancies treated with a single surgeryto achieve 5-year disease-free survival (DFS); cured cervical carcinoma in situ,non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasivetumors), Tis (carcinoma in situ) and T1 (tumor-invasive basement membrane)];
2. adverse effects due to any prior treatment have not been restored to CTCAE 5.0 ≤level 1 (except for toxicity where the investigator determines that there is nosafety risk);
3. Major surgical treatment, incision biopsy, or significant traumatic injury werereceived within 28 days prior to study treatment
4. Long-term unhealed wounds or fractures
5. Arteriovenous thrombotic events within 6 months, such as cerebrovascularaccidents;
6. Those who have a history of psychotropic substance abuse and cannot quit or havea mental disorder;
7. Subjects with any severe and/or uncontrolled medical conditions, including:
8. Unsatisfactory blood pressure control (systolic blood pressure ≥ 150mmHg ordiastolic blood pressure ≥100 mmHg);
9. Have grade ≥2 myocardial ischemia or myocardial infarction, arrhythmias (including QTc ≥ 450 ms (male) in men and QTc ≥ 470 ms (female)) and grade ≥congestive heart failure grade 2 (New York Heart Association (NYHA) grade);
10. Active or uncontrolled severe infection (≥ CTC AE grade 2 infection) orunexplained fever > 38.5°C;
11. Liver cirrhosis, active hepatitis Note: Active hepatitis (hepatitis Breference: HBsAg positive and HBV (hepatitis B virus) DNA detection value ofmore than 1000 copies /mL; Hepatitis C reference: HCV (hepatitis C virus)antibody positive, and HCV virus titer test value above the upper limit ofnormal);
12. Known to have syphilis;
13. Renal failure requires hemodialysis or peritoneal dialysis
14. A history of immunodeficiency, including HIV positive or other acquired orcongenital immunodeficiency diseases, or a history of organ transplantation;
15. Poor diabetes control [fasting blood glucose (FBG) > 10mmol/L]
16. Urine routine indicated urine protein ≥++, and confirmed 24 hours urineprotein quantity > 1.0 g
17. People who have epilepsy and need treatment

• Tumor related symptoms and treatment

1. Study history of surgery, chemotherapy, radiotherapy, or other anticancer therapywithin 4 weeks prior to the start of treatment (washout period from the end ofthe last treatment)；
2. progress during or within 6 months of completion of systemic therapy (includinginduction therapy, concurrent radiotherapy, adjuvant therapy) for locallyadvanced disease;
3. Secondary radiotherapy was performed for local recurrent lesions;
4. Received Chinese patent drugs with anti-tumor indications specified in theChinese National Medical Product Administration approved drug instructions within 1 week before the study treatment;
5. Have received relevant immunotherapy drugs in the past;
6. where imaging (CT or MRI) shows that the tumor has invaded important bloodvessels, or the investigator determines that the tumor is highly likely to invadeimportant blood vessels and cause fatal massive bleeding during the follow-upstudy period;
7. Uncontrolled pleural effusion, pericardial effusion, or ascites requiringrepeated drainage (investigator's judgment)
8. Subjects with known central nervous system metastatic and/or cancerousmeningitis;

• Research and treatment related:

1. Study history of live attenuated vaccine vaccination within 28 days before thestart of treatment or planned live attenuated vaccine vaccination during thestudy period;
2. Patients with a definite tendency to bleed or clinically significant bleedingsymptoms, including but not limited to gastrointestinal bleeding, nasal bleeding,and hemorrhagic disease or coagulopathy within 28 days prior to initialmedication;
3. People who have experienced severe hypersensitivity after the use of monoclonalantibodies, or are allergic to known components of the drug under study;
4. Study of active autoimmune diseases requiring systemic treatment that occurredwithin 2 years prior to initiation of treatment;
5. Have been diagnosed with immunodeficiency or are receiving systemicglucocorticoid therapy or any other form of immunosuppressive therapy (dose > 10mg/ day prednisone or other efficacy hormone) and continue to use within 2weeks before the study therapy begins;

• Participated in clinical trials of other antitumor drugs within 4 weeks before thefirst medication;
• Subjects who, in the judgment of the investigator, have concomitant diseases thatseriously endanger the safety of the subjects or affect the completion of the study,or subjects who are not suitable for inclusion for other reasons.