Overview
This is a prospective, single-arm, phase II study. It aims to evaluate whether neoadjuvant targeted therapy combined with immunotherapy and chemotherapy is effective and safe in patients with locally advanced, resectable head and neck squamous cell carcinoma (HNSCC).
Description
This clinical trial adopts a prospective, single-arm, phase II trial design. Each neoadjuvant treatment cycle will be three weeks long. Patients will receive up to 3 cycles of neoadjuvant therapy, including nimotuzumab, toripalimab, nab-paclitaxel, and cisplatin. After screening, eligible patients will be enrolled in the study. Patients will receive nimotuzumab weekly on days 1, 8, and 15; toripalimab on day 1; and chemotherapy with nab-paclitaxel and cisplatin on day 1 every 3 weeks for 3 cycles. Radical surgery will be performed approximately 1 month after the last neoadjuvant treatment. Postoperative adjuvant therapy will be selected by the investigator based on high-risk pathological factors. Patients will undergo regular follow-up visits, and researchers will collect data on efficacy and safety. The primary endpoint is the major pathological response (MPR) rate. Secondary endpoints include pathological complete response (pCR) rate, objective response rate (ORR), 2-year overall survival (OS) rate, 2-year event-free survival (EFS) rate, 2-year locoregional control (LRC) rate, quality of life, safety, and prognostic biomarkers. Short-term outcomes will be assessed according to RECIST 1.1, and adverse events will be evaluated using NCI-CTCAE 6.0. Approximately 86 patients aged 18-75 years with stage III-IVB resectable HNSCC will be enrolled. Enrollment is expected to be completed within 2 years, with at least 2 years of follow-up after the last patient is enrolled.
Eligibility
Inclusion Criteria:
- Age 18-75 years.
- Histologically or cytologically confirmed resectable stage III-IVB head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, or larynx according to the AJCC 9th edition.
- For oropharyngeal cancer, tumor tissue must be available for HPV/P16 testing (testing is not required if previously performed).
- Tumor tissue (from the primary tumor or resected tumor) must be available for EGFR and PD-L1 immunohistochemical testing (testing is not required if previously performed); genetic testing may be performed when necessary.
- ECOG performance status 0-1.
- At least one measurable lesion according to RECIST 1.1.
- Expected survival ≥6 months.
- Adequate hematologic function: white blood cell count ≥3 × 10\^9/L; absolute neutrophil count ≥1.5 × 10\^9/L; platelet count ≥100 × 10\^9/L; hemoglobin ≥90 g/L.
- Adequate renal function: serum creatinine ≤1.5 × ULN or creatinine clearance (CrCl) \>50 mL/min (using the Cockcroft-Gault formula):
- Female CrCl = (140 - age) × body weight (kg) × 0.85 / (72 × Scr mg/dL); Male CrCl = (140 - age) × body weight (kg) × 1.00 / (72 × Scr mg/dL).
- Adequate hepatic function: total serum bilirubin ≤1.5 × ULN; aspartate aminotransferase (AST) ≤2.5 × ULN; alanine aminotransferase (ALT) ≤2.5 × ULN.
- Women of childbearing potential must have a negative pregnancy test within 2 weeks before the start of study treatment and must not be breastfeeding. -Female participants must agree to use effective contraception during the study and for 6 months after the last dose of study drug. Male participants must agree to use effective contraception during the study and for 6 months after the last dose of study drug.
- Participants must voluntarily agree to participate, provide written informed consent, and be able to comply with the study visits and procedures specified in the protocol.
Exclusion Criteria:
- Prior radiotherapy or chemotherapy; prior immunotherapy targeting PD-1/PD-L1; prior EGFR monoclonal antibody, EGFR-TKI, or anti-angiogenic therapy.
- Treatment with systemic or local corticosteroids within 4 weeks before enrollment.
- HIV-positive; HBsAg-positive with detectable HBV DNA (quantitative ≥1000 copies/mL); or positive blood screening for chronic hepatitis C (HCV antibody-positive) with detectable HCV RNA.
- Participation in another interventional clinical trial within 30 days before screening.
- History of other malignancies (except cured basal cell carcinoma of the skin). History of primary immunodeficiency.
- Presence of poorly controlled concomitant diseases (e.g., heart failure, severe pulmonary disease, severe liver disease, psychiatric disorders, etc.).
- Major surgery within 90 days before the first dose of study drug or planned surgery.
- Known allergy to any study drug or its components.
- Pregnancy (confirmed by blood or urine HCG) or breastfeeding; or participants of childbearing potential (both male and female) who are unwilling or unable to use effective contraception until at least 6 months after the last study treatment.
- Any condition that, in the investigator's opinion, makes the participant unsuitable for the study.
- Unwillingness to participate in the study or inability to sign informed consent.
Receipt of a live vaccine within 30 days before study drug administration.
