Intra-arterial Chemotherapy Combined with Radiotherapy and Immunotherapy for HNSCC

Inclusion Criteria:

• Patients with T4bNanyM0 Head and neck squamous cell carcinoma (hypopharyngealcancer, laryngeal cancer, oropharyngeal cancer or oral cavity) with a confirmeddiagnosis by histology and/or cytology;

• Expected survival ≥3 months, with adequate organ function;

• Investigators believe they can safely receive treatment with PD-1 combined withplatinum and albumin-bound paclitaxel;

• Age ≥18 years;

• ECOG score of 0-1;

• Measurable disease as defined by RECIST v1.1;

• Adequate bone marrow reserve and organ function: Absolute neutrophil count (ANC) ≥1,000/microliter (mcL), platelets ≥75,000/mcL, hemoglobin ≥8g/dL, withouttransfusion or dependence on erythropoietin (EPO) (within 7 days after assessment);

• Renal function: Serum creatinine ≤1.5 times the upper limit of normal (ULN) ORmeasured or calculated creatinine clearance ≥60mL/min with creatinine levels > 1.5times the institutional ULN. (GFR can also be used in place of creatinine or CrCl).Creatinine clearance should be calculated according to institutional standards;

• Liver function: For subjects with a total bilirubin level >1.5 ULN, serum totalbilirubin ≤1.5 times ULN or direct bilirubin ≤ULN; For patients with livermetastases, aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5 times ULN OR ≤5 times ULN; Albumin > 2.5 mg/dL;

• Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN, if the subject is receiving anticoagulant therapy, PT or PTT shouldbe within the permissible range of the anticoagulant used;

• Females should agree to use contraceptive measures (such as intrauterine device (IUD), oral contraceptives, or condoms) during the study and for 6 months after thestudy ends; Negative serum or urine pregnancy test within 7 days before study entry,and must be non-lactating patients; Males should agree to use contraceptive measuresduring the study and for 6 months after the study ends.

Exclusion Criteria:

• Patients with a history of prior immunotherapy, radiotherapy, and treatment withEGFR monoclonal antibodies;

• Patients with a history of other (including unknown primary) malignant tumors withinthe past 5 years;

• Patients who are intolerant to radiotherapy post-surgery;

• Patients known to be allergic to the study medication or its active ingredients,excipients;

• Patients with any unstable systemic diseases, including but not limited to: severeinfections, uncontrolled diabetes, unstable angina, cerebrovascular accidents ortransient ischemic attacks, myocardial infarction, congestive heart failure, seriousarrhythmias requiring medication, liver, kidney, or metabolic disorders;

• Patients with potential immune deficiencies, chronic infections, including HIV,hepatitis, tuberculosis (TB), or autoimmune diseases;

• Patients with potential hematological issues, including bleeding disorders, knownprior gastrointestinal bleeding requiring intervention within the past 6 months,active pulmonary embolism or deep vein thrombosis (DVT) that is unstable onanticoagulation regimens;

• A history or any evidence of active noninfectious pneumonia;

• Known active central nervous system (CNS) metastases and/or leptomeningeal diseaseor carcinomatous meningitis. Subjects with previously treated brain metastases mayparticipate if they are stable (no evidence of imaging progression for at least fourweeks prior to the first trial treatment and any neurological symptoms have returnedto baseline), with no new or enlarging evidence of brain metastases, and are not onsteroids for at least 7 days prior to trial treatment. This exception does notinclude carcinomatous meningitis, which is excluded regardless of clinicalstability;

• Concurrent use (or receipt) of medications within 7 days prior to Day 1 of Cycle 1that may affect drug metabolism;

• Pregnant or breastfeeding, or expecting to become pregnant or father a child duringthe anticipated trial period;

• Any uncontrollable concomitant diseases, including but not limited to persistent oractive infections, symptomatic congestive heart failure, unstable angina,arrhythmias;

• Prolonged corrected QT (QTc) interval > 475 ms on screening EKG;

• Ejection fraction <40% on 2D echocardiogram (ECHO) at screening;

• Any serious medical or psychiatric illness/condition, including substance usedisorders, that may interfere with or limit adherence to studyrequirements/treatment in the investigator's judgment;

• Active autoimmune disease requiring systemic treatment in the past 2 years (i.e.,the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).Replacement therapies (e.g., thyroid hormone, insulin, or physiologic corticosteroidreplacement for adrenal or pituitary insufficiency, etc.) are not considered a formof systemic treatment.