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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 32
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •HGB ≥ 90 g/L;
- •NEUT ≥ 1.5 × 10⁹/L;
- •PLT ≥ 80 × 10⁹/L;
- •Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);
- •ALT and AST ≤ 2.5 × ULN; in cases of liver metastases, ALT and AST ≤ 5 × ULN;
- •Endogenous creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula);
- •Urinary protein < (++), or 24-hour urinary protein < 1.0 g.
- •Normal coagulation function with no active bleeding
- •International Normalized Ratio (INR) ≤ 1.5;
- •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.
排除标准
- •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);
- •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.
研究组 & 干预措施
Neoadjuvant Triplet Combination Therapy Arm
干预措施: Radical Surgical Resection (Procedure)
Neoadjuvant Triplet Combination Therapy Arm
干预措施: Dalpiciclib Isethionate (Drug)
Neoadjuvant Triplet Combination Therapy Arm
干预措施: Cisplatin (Drug)
Neoadjuvant Triplet Combination Therapy Arm
干预措施: Adebrelimab Injection (Drug)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: At time of surgical resection (approximately 6 weeks after 2 cycles neoadjuvant treatment)
Percentage of subjects achieving pathological complete response in primary tumor and regional lymph nodes after neoadjuvant therapy (no viable tumor cells in surgical specimen)
次要结局
- Major Pathological Response (MPR) Rate(At surgical resection)
- Objective Response Rate (ORR)(At the end of Cycle 2 (each neoadjuvant cycle is 28 days))
- Disease Control Rate (DCR)(At the end of Cycle 2 (each neoadjuvant cycle is 28 days))
- Progression-Free Survival (PFS)(Up to 36 months from enrollment)
- 1-Year Overall Survival (1y-OS) Rate(12 months post first treatment)
- Incidence and Severity of Treatment-Related Adverse Events (TRAEs)(From screening through 30 days after final study drug dose)