Neoadjuvant Treatment of Locally Advanced HNSCC With Pertuzumab Combined With Lenvatinib.

Safety and Efficacy of Pertuzumab Combined With Lenvatinib for Neoadjuvant Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Single-Arm, Single-Center Clinical Study.

A single-arm, single-center clinical trial evaluating efficacy (Phase #)

Study Overview

• Status: Enrolling by invitation
• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Drug: A single-arm, single-center clinical trial evaluating efficacy

Detailed Description

The investigators designed a single-center, single-arm clinical trial. In this trial, patients with resectable locally advanced head and neck squamous cell carcinoma (Stage III-IV) were enrolled as subjects. After obtaining informed consent, eligible patients who met the inclusion and exclusion criteria were selected to receive neoadjuvant standard therapy with pertuzumab combined with lenvatinib. After 2-4 cycles of treatment, surgical intervention was performed, followed by adjuvant therapy (which may include systemic drug therapy and radiotherapy) as determined by the investigators.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1）Understand and voluntarily sign the written informed consent form, and agree to comply with the requirements specified in the protocol.

2) The patient is a first-line patient who has not undergone systemic treatment or radiotherapy for head and neck squamous cell carcinoma.

3) Age ≥18 years and ≤75 years 4) Initial diagnosis confirmed by cytology or histology of squamous cell carcinoma of the head and neck originating from the oral cavity, oropharynx, hypopharynx, or larynx 5) AJCC 8th edition clinical stage III-IVA 6) According to RECIST v1.1, at least one measurable lesion is required. 7) The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1, with no deterioration within 2 weeks prior to enrollment for the study treatment.

8) Good bone marrow function, defined as meeting all the following criteria and not requiring supportive transfusion or growth factor (CSF, EPO, etc.) therapy within 3 weeks (21 days) prior to administration or within 2 weeks (14 days) prior to administration:

• Hemoglobin (Hb) ≥9.0 g/dL (90 g/L)
• Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L
• Total platelet count (PLT) ≥100×10⁹/L 9) Good liver function, defined as all of the following conditions:
• Total bilirubin (TBIL) ≤1.5×ULN (upper limit of normal); for subjects with elevated serum bilirubin due to underlying Gilbert syndrome, familial benign non-conjugate hyperbilirubinemia, or documented hepatic metastases, TBIL ≤2.5×ULN

• Aspartate aminotransferase (AST) (serum aspartate aminotransferase, SGOT) and alanine aminotransferase (ALT) (serum alanine aminotransferase, SGPT) ≤ 2.5×ULN; in cases of liver metastases, ALT or AST ≤ 3.0×ULN 10) Coagulation function: International Normalized Ratio (INR) or Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN (except for subjects receiving anticoagulant therapy, whose anticoagulant levels should be within the therapeutic range). If the subject is receiving anticoagulant therapy, the investigator should closely monitor these laboratory parameters.

  11) Good renal function, defined as creatinine ≤1.5×ULN or serum creatinine clearance (Ccr) ≥50 mL/min (creatinine clearance should be calculated using the corrected Cockcroft-Gault formula. If local guidelines are unavailable, creatinine clearance can be calculated as: Ccr = [(140-age) × body weight (kg) × (0.85 for women only)] / (72 × serum creatinine) (in the absence of significant and uncorrectable electrolyte imbalances).

  12) Baseline left ventricular ejection fraction (LVEF) ≥ 50% as measured by multi-gate acquisition (MUGA) or echocardiography (ECHO).

  13) Fertile female and male participants must agree to use adequate contraception during the study medication period and for 180 days after the last treatment.

• Fertile women (those who have not undergone surgical sterilization or have been postmenopausal for less than 1 year) are willing to adopt adequate and reliable contraceptive measures during the study period until 180 days after the last dose of the study drug, such as avoiding heterosexual intercourse, undergoing sterilization procedures, using oral contraceptives, injectable contraceptives, intrauterine devices (IUDs), or condoms.
• Male subjects must be willing to use latex condoms during any sexual contact with a fertile female, even after successful vasectomy, during the treatment period with the investigational drug and for 180 days after the last treatment. Fertile males are advised to consider obtaining a semen sample prior to the first dose of the drug and storing it for potential future conception.

Exclusion Criteria:

1. Pregnant or lactating women
2. Previous history of other malignant tumors within the past 5 years, excluding previously cured basal cell carcinoma of the skin and differentiated thyroid carcinoma.
3. Oral and pharyngeal carcinoma with positive HPV test results
4. Known hypersensitivity to the investigational drugs pertuzumab or lenvatinib
5. Currently using and cannot discontinue potent CYP3A4 inhibitors or inducers
6. Active autoimmune diseases or history of autoimmune diseases
7. History of immunodeficiency, including HIV-positive status, other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and bone marrow transplantation
8. History of mental illness or substance abuse
9. Peripheral neuropathy of grade ≥2 (based on CTCAE 5.0)
10. History of severe cardiac insufficiency, stroke, or transient ischemic attack (TIA) within 6 months prior to enrollment. History of ventricular tachycardia or torsades de pointes. Any clinically significant abnormalities in the rhythm, conduction, or morphology of resting ECG, such as QTcF> 450 ms in males, QTcF> 470 ms in females, complete left bundle branch block, or third-degree atrioventricular block. Presence of clinically significant cardiac disease, including acute myocardial infarction (MI) occurring within 6 months prior to the first study treatment, congestive heart failure (NYHA class III or IV), unstable angina, or arrhythmias requiring treatment. Note: Subjects with arrhythmias may be enrolled if they are receiving antiarrhythmic drug therapy and the screening ECG shows a controlled rhythm.
11. Study of pulmonary embolism or deep vein thrombosis occurring within 3 months prior to the first drug administration.
12. Known history of malignancy (excluding patients who have successfully undergone curative treatment for skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, carcinoma in situ, or papillary thyroid carcinoma), unless the subject has received potentially curative treatment and has had no disease recurrence within 5 years from the start of treatment.
13. Uncontrolled or poorly controlled hypertension (e.g., systolic blood pressure>160 mmHg or diastolic blood pressure>100 mmHg) or hyperglycemia (fasting blood glucose>8.9 mmol/L, or glycated hemoglobin (HbA1c)>8% in type 1 DM subjects).

14）Known active hepatitis B or hepatitis C. Active hepatitis B is defined as known HBsAg positivity with HBV DNA ≥500 IU/mL. Active hepatitis C is defined as known hepatitis C antibody positivity and known quantitative HCV RNA results greater than the detection limit. Other severe liver diseases are present, including chronic autoimmune liver disease, primary biliary cholangitis or cirrhosis, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH).

15）Subjects with a positive pregnancy test or those who are breastfeeding. Female and male subjects who are not expected to use adequate contraception during the treatment period and within 180 days after the last treatment administration.

The circumstances that the researchers assessed as unsuitable for inclusion in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Active Comparator: A single-arm, single-center clinical trial evaluating efficacy (Phase #); Combination therapy regimen: Pertuzumab combined with lenvatinib for neoadjuvant treatment Each 21-day period constitutes one treatment cycle, with pertuzumab administered at a dose of 3 mg/kg.(Up to 200 mg) Q3W, lenvatinib 8 mg QD.Total of 2-4 cycles.The subjects will undergo surgery subsequently. Subsequently, adjuvant therapy was administered.

Drug: A single-arm, single-center clinical trial evaluating efficacy; Combination therapy regimen: Pertuzumab combined with lenvatinib for neoadjuvant treatment Each 21-day period constitutes one treatment cycle, with pertuzumab administered at a dose of 3 mg/kg.(Up to 200 mg) Q3W, lenvatinib 8 mg QD.Total of 2-4 cycles.The subjects will undergo surgery subsequently. Subsequently, adjuvant therapy was administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Progression Rate (MPR)	Pathological complete response rate of primary tumor after neoadjuvant therapy	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	Pathological complete response rate of primary tumor after neoadjuvant therapy	up to 6 months
objective response rate (ORR) in neoadjuvant therapy	The decline phase following neoadjuvant therapy The treating physician will evaluate the tumor stage according to the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition) after neoadjuvant therapy.	up to 6 months
umor regression rate	The decline phase following neoadjuvant therapy The treating physician will evaluate the tumor stage according to the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition) after neoadjuvant therapy.	up to 6 months
organ preservation rate	The decline phase following neoadjuvant therapy The treating physician will evaluate the tumor stage according to the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition) after neoadjuvant therapy.	up to 6 months
2-year EFS rate	EFS is defined as the time from the initial treatment date to the first recorded event date, including disease progression. Progression, local or distant metastasis as assessed by imaging or biopsy, or death from any cause, whichever occurs first.	up to 2 years
2-year OS rate	OS was defined as the time from the start of treatment to death from any cause.	2 years

Collaborators and Investigators

• Sponsor: Zhejiang Provincial People's Hospital
• Investigators: Study Chair: Jiajie Xu, Zhejiang Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: April 19, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: squamous cell carcinoma of the head and neck
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: KY2025224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No