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

A Prospective, Open-Label, Phase II Clinical Trial of 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) <50%;
• Active or uncontrolled severe infection (≥CTCAE v5.0 Grade 2 infection); 9. Known human immunodeficiency virus (HIV) infection. History of clinically significant liver disease, including viral hepatitis [known hepatitis B virus (HBV) carriers must be free of active HBV infection, i.e., HBV DNA positive (>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.