Iparomlimab and Tuvonralimab Plus Hypofractionated Radiotherapy and Chemotherapy for HAHNSCC

Inclusion Criteria: 1. Signed a written informed consent form and understands and agrees to comply with the study requirements and visit schedule. 2. Male or female subjects aged ≥18 and ≤75 years at the time of signing informed consent. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1. 4. Histologically or cytologically confirmed stage III-IVB head and neck squamous cell carcinoma as assessed by the investigator. 5. No prior systemic therapy for head and neck squamous cell carcinoma (including chemotherapy, EGFR monoclonal antibodies, anti-PD-1 or anti-PD-L1 antibodies, anti-CTLA-4 antibodies, or other immune checkpoint inhibitors). 6. At least one measurable target lesion per RECIST v1.1 criteria. 7. Estimated life expectancy ≥12 weeks. 8. Adequate bone marrow and organ function (without receiving any cellular products, blood components, colony-stimulating factors, or cytokine therapy within 14 days prior to laboratory testing): 1. Hematology: ANC ≥1.5 × 10⁹/L or within normal range; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L. 2. Liver function: Total bilirubin ≤1.5 × ULN; for Gilbert's syndrome, TBIL ≤3 × ULN; AST and ALT ≤2.5 × ULN in patients without liver metastasis, or ≤5 × ULN in those with liver metastasis; albumin ≥28 g/L. 3. Renal function: Serum creatinine ≤1.5 × ULN, or creatinine clearance (CCR) ≥60 mL/min (calculated via Cockcroft-Gault formula or measured via 24-hour urine collection); urine dipstick protein \<2+. For subjects with baseline ≥2+ proteinuria, a 24-hour urine test must show \<1 g of protein (if both tests are done, the 24-hour result will determine eligibility). 4. Coagulation: International normalized ratio (INR) ≤1.5; activated partial thromboplastin time (APTT) ≤1.5 × ULN. 9. Subjects who are infertile or agree to use at least one highly effective contraceptive method during the study (starting 14 days before screening or first dose, whichever occurs earlier, and continuing until 180 days after the last dose of study drug). Exclusion Criteria: 1. History of allergy to any component of anti-PD-1/CTLA-4 antibodies or cisplatin. 2. History or presence of another malignancy (except those cured and without recurrence for more than 5 years, including basal cell carcinoma, carcinoma in situ of the cervix, and papillary thyroid carcinoma). 3. Uncontrolled cardiac symptoms or diseases, including: 1. New York Heart Association (NYHA) class II or higher heart failure. 2. Unstable angina. 3. Myocardial infarction within the past year. 4. Clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention. 4. Prior treatments, including: 1. Previous treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies. 2. Use of any investigational drug within 4 weeks prior to the first dose of study drug. 3. Concurrent participation in another clinical trial, unless it is an observational (non-interventional) study. 4. Requirement for systemic corticosteroid therapy (≥10 mg prednisone or equivalent/day) or other immunosuppressive drugs within 2 weeks prior to the first dose of study drug, except for topical or inhaled steroids, or prophylaxis for nausea, vomiting, or allergic reactions. Other special circumstances should be discussed with the investigator. In the absence of active autoimmune disease, inhaled or topical corticosteroids and physiologic replacement doses of adrenal corticosteroids equivalent to \>10 mg/day prednisone are allowed. 5. Receipt of an antitumor vaccine or live vaccine within 4 weeks before the first dose of study drug. 6. Major surgery or severe trauma within 4 weeks before the first dose of study drug. 5. Failure to recover from previous antitumor therapy to ≤Grade 1 per CTCAE criteria (except for alopecia and residual neuropathy related to prior platinum therapy), or laboratory results not meeting the inclusion/exclusion thresholds. 6. Severe infection (CTCAE \> Grade 2) within 4 weeks before the first dose of study drug, including severe pneumonia, bacteremia, infections requiring hospitalization, evidence of active pulmonary inflammation on baseline imaging, symptoms or signs of infection within 4 weeks prior to first dose, or requiring oral or IV antibiotics. 7. Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). However, patients with autoimmune hypothyroidism on stable replacement therapy, type I diabetes on stable insulin therapy, vitiligo, or childhood asthma/allergies resolved in adulthood without intervention are eligible. 8. History of immunodeficiency, including HIV positivity, acquired or congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation. 9. History of interstitial lung disease (excluding radiation pneumonitis not requiring steroids) or noninfectious pneumonitis. 10. Active tuberculosis based on history or CT imaging; active TB within 1 year prior to enrollment; or remote history of TB (\>1 year prior) without appropriate treatment. 11. Active hepatitis B (HBV DNA ≥500 IU/mL or ≥2500 copies/mL) or active hepatitis C (anti-HCV positive with HCV RNA above lower limit of detection). 12. History of substance abuse, alcohol abuse, or drug dependence. 13. Pregnant or breastfeeding women. 14. Subjects whom the investigator considers unsuitable due to factors that may lead to early study discontinuation, such as severe comorbidities requiring concurrent treatment (including psychiatric disorders), significantly abnormal laboratory values, or family/social conditions that may affect subject safety or data collection.