HNSCC
Conditions
Brief summary
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.
Interventions
Dose: 1200 mg Route: Intravenous Infusion Schedule: Day 1 of each 21-day cycle, every 3 weeks for 2 cycles total Description: Intravenous infusion over 30 minutes (20-60 min window), no dose reduction allowed; suspend or permanently discontinue per immune-related adverse events.
DRUGDalpiciclib Isethionate
100mg/125mg, Schedule: Days 1-21 of every 28-day cycle, continuous oral administration Description: Dose modification per CTCAE v5.0 toxicity grading; permanent discontinuation for ≥2 grade interstitial lung disease, grade 4 hepatotoxicity.
DRUGCisplatin
Dose: 75 mg/m² Route: Intravenous drip Schedule: Day 1 of each 21-day cycle, every 3 weeks for 2 cycles total Description: Dose reduced to 40mg/m² if creatinine clearance 40-50 mL/min; discontinue cisplatin if CrCl \<40 mL/min; 20% dose reduction for grade 3-4 related toxicities.
PROCEDURERadical Surgical Resection
Timing: 4-6 weeks after completion of 2 neoadjuvant cycles Description: Curative surgical resection of primary tumor and regional lymph nodes per standard head and neck oncology guidelines.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1-Year Overall Survival (1y-OS) Rate | 12 months post first treatment | Percentage of subjects alive 12 months after first dose of neoadjuvant therapy |
| Incidence and Severity of Treatment-Related Adverse Events (TRAEs) | From screening through 30 days after final study drug dose | All adverse events graded per NCI CTCAE v5.0 from informed consent signing to 1 month after last study drug administration; summarize frequency, grade, causality and resolution |
| Progression-Free Survival (PFS) | Up to 36 months from enrollment | Time from first study drug administration to first documentation of disease progression (local/regional/distant) or death from any cause |
| Major Pathological Response (MPR) Rate | At surgical resection | Proportion of patients with ≤10% residual viable tumor cells in surgical specimen |
| Objective Response Rate (ORR) | At the end of Cycle 2 (each neoadjuvant cycle is 28 days) | Percentage of participants with confirmed Complete Response (CR) or Partial Response (PR) per RECIST 1.1 on post-neoadjuvant contrast-enhanced CT |
| Disease Control Rate (DCR) | At the end of Cycle 2 (each neoadjuvant cycle is 28 days) | Proportion of patients with CR, PR or Stable Disease (SD) per RECIST 1.1 |
Contacts
CONTACTChunhua She Chunhua She
Outcome results
None listed