Adebrelimab Combined With Dalpiciclib Isethionate Plus Chemotherapy for Neoadjuvant Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma

This single-center, open-label Phase II trial aims to evaluate the efficacy and safety of neoadjuvant combination therapy with Adebrelimab (anti-PD-L1), Dalpiciclib Isethionate (CDK4/6 inhibitor), and cisplatin chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC). A total of 32 eligible subjects will receive 2 cycles of triplet neoadjuvant treatment prior to radical surgery. The primary endpoint is the pathological complete response (pCR) rate following neoadjuvant therapy; secondary endpoints include major pathological response (MPR), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), 1-year overall survival (1y-OS), and treatment-related adverse events (TRAEs). The exploratory objectives analyze correlations between biomarkers (oral microbiome, CDKN2A/B deletion, CDK4/6 amplification, and PD-L1 expression) and therapeutic efficacy or prognosis. Subjects will receive long-term tumor and survival follow-up after surgery until disease progression, death, loss to follow-up, or the end of study.

Inclusion Criteria: * Patients aged ≥18 years; * Males or females who are not pregnant or breastfeeding; * ECOG performance status of 0-1, with no deterioration within the past 7 days; * Patients with histologically confirmed, locally advanced, resectable head and neck squamous cell carcinoma; * Patients who have not previously received any systemic treatment regimens for this cancer type; * Patients receiving neoadjuvant therapy must have evaluable lesions; * Adequate organ and bone marrow function, with laboratory test results meeting the following requirements: 1. HGB ≥ 90 g/L; 2. NEUT ≥ 1.5 × 10⁹/L; 3. PLT ≥ 80 × 10⁹/L; 4. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); 5. ALT and AST ≤ 2.5 × ULN; in cases of liver metastases, ALT and AST ≤ 5 × ULN; 6. Endogenous creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); 7. Urinary protein \< (++), or 24-hour urinary protein \< 1.0 g. * Normal coagulation function with no active bleeding 1. International Normalized Ratio (INR) ≤ 1.5; 2. Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times the upper limit of normal (ULN). * Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and must voluntarily use appropriate contraception during the observation period and for 8 weeks after the last administration of the study drug; for men, they must be surgically sterilized or agree to use appropriate contraception during the observation period and for 8 weeks after the last administration of the study drug. * Expected survival ≥ 12 months. * Patients must voluntarily enroll in this study and sign an Informed Consent Form (ICF). * Patients are expected to demonstrate good compliance and be able to follow up on efficacy and adverse reactions as required by the protocol. Exclusion Criteria: * Previous receipt of any antitumor therapy for head and neck squamous cell carcinoma; * Administration of a live vaccine within 4 weeks prior to enrollment or likely to occur during the study period; * Active autoimmune disease or a history of autoimmune disease within 4 weeks prior to enrollment; * Previous allogeneic bone marrow or organ transplantation; * Uncontrolled hypertension prior to enrollment, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥90 mmHg; * Any disease or condition prior to enrollment that affects drug absorption; * Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Class \>2 congestive heart failure; ventricular arrhythmias requiring medication; LVEF (left ventricular ejection fraction) \1×10⁴ copies/mL or \>2,000 IU/mL); known hepatitis C virus (HCV) infection with HCV RNA positive (\>1×10³ copies/mL) ; * Any other disease, clinically significant metabolic abnormalities, physical examination abnormalities, or laboratory test abnormalities that, in the investigator's judgment, give reason to suspect that the patient has a condition or state that makes them unsuitable for the study drug (e.g., a history of epileptic seizures requiring treatment), or that will affect the interpretation of study results, or that places the patient at high risk; * Patients whom the investigator deems unsuitable for enrollment in this study.