Neoadjuvant and Adjuvant Toripalimab and Cetuximab in Patients With Recurrent, Resectable Squamous Cell Carcinoma of Head and Neck: a Prospective, Single-arm,Phase II Study

• Status: Recruiting
• Trial end date: 2026-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This study is the first clinical study of Neoadjuvant and Adjuvant treatment of head and neck squamous cell carcinoma with drugs targeting EGFR signaling pathway combined with PD-1 inhibitors, which explores the new combination therapies urgently needed in clinical practice and lays a foundation for subsequent studies, with important scientific research significance and clinical value.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• Treatments: Cetuximab

Criteria

Inclusion Criteria:

1. age 18-75 years old, regardless of gender

2. histologically or cytologically confirmed and surgically curable recurrent localized squamous carcinoma of the head and neck (tumor primary sites are oropharynx, oral cavity, hypopharynx, and larynx) without any antitumor systemic therapy during the recurrent stage (allowed as part of treatment for locally advanced tumors and requiring more than 6 months between the end of treatment and the signing of the informed consent)

3. an ECOG score of 0 or 1.

4. an expected survival of ≥ 12 weeks.

5. have at least one measurable lesion according to RECIST 1.1 criteria, and a previously treated lesion with radiation therapy, if disease progression has occurred, may also be a measurable lesion.

6. availability of tumor tissue for PD-L1 detection (paraffin specimens less than 2 years old or fresh tumor tissue)

7. patients with oropharyngeal carcinoma provide a test status for P16, using the IHC method.

8. Organ function levels must meet the following requirements (14 days prior to the first dose of study drug):

Bone marrow:absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets (PLT) ≥ 100×109/L, hemoglobin (HB) ≥ 9g/dL (not transfused or receiving component blood within 14 days prior to testing); Liver: serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal value (in case of liver metastases, AST and ALT ≤ 5 times the upper limit of normal value are allowed); serum creatinine ≤ 1.5 times the upper limit of normal value and endogenous creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula) Gault formula); International normalized ratio (INR), activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of normal (only for patients not receiving anticoagulation; patients receiving anticoagulation should keep anticoagulants within the therapeutically required range); Thyroid stimulating hormone (TSH) ≤ 1 x ULN (if abnormal FT3 and FT4 levels should be examined at the same time; if FT3 and FT4 levels are normal, the patient can be enrolled) Urine protein ≤ 1+, if urine protein > 1+, 24-hour urine protein measurement should be collected, and its total amount should be ≤ 1 gram; Normal cardiac function, i.e. normal or abnormal ECG examination without clinical significance and cardiac ultrasound showing left ventricular ejection fraction (LVEF) >50%.

9. female subjects of reproductive potential must have a negative serum pregnancy test prior to the first dose of the trial drug; 10. male or female subjects of reproductive potential must be using a highly effective method of contraception (e.g., oral contraceptive pills, intrauterine device, abstinence from sexual intercourse, or barrier method of contraception in combination with spermicide) throughout the trial and continue to use contraception for 90 days after the end of treatment.

11. Subjects voluntarily enrolled in the study, signed an informed consent form, were compliant and cooperative with follow-up.

Exclusion Criteria:

1. with distant metastatic lesions or localized lesions not indicated for surgery (patients with stage IVb or IVc)

2. have progressed within 6 months after systemic therapy directed at locally advanced squamous head and neck cancer.

3. a prior history of primary nasopharyngeal cancer tumor.

4. patients who have participated or are participating in a clinical trial of another drug/therapy within 4 weeks prior to the first dose of the study drug.

5. underwent/received major surgery or have not recovered from the side effects of such surgery, live vaccination, immunotherapy within 4 weeks prior to the first dosing of the study drug, and radiation therapy within 2 weeks.

6. receiving any other concurrent antitumor therapy.

7. the patient has any active autoimmune disease or a history of autoimmune disease (e.g., the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism; vitiligo that does not require systemic therapy may be included; asthma that has completely resolved in childhood and does not require any intervention in adulthood may be included; patients requiring bronchial (asthma that requires medical intervention with bronchodilators cannot be included).

8. patients who are on immunosuppressive, or systemic hormone therapy for immunosuppressive purposes (doses >10 mg/day of prednisone or other equipotent hormones) and continue to use them within 2 weeks prior to enrollment

9. a history of other malignancies within the past 5 years, with the exception of cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, early stage prostate cancer and carcinoma in situ of the cervix

10. patients who have received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin, etc., within 1 week prior to the first dose of the study drug

11. prior treatment with PD-1/PD-L1/PD-L2/CTLA-4 antibodies or activating or inhibitory agents targeting T-cell receptors (e.g., OX40, CD137)

12. prior drug treatment with cetuximab.

13. positive test results for HIV antibodies or syphilis spirochete antibodies

14. Patients with active hepatitis B or C:

If HBsAg or HBcAb is positive, add HBV DNA test (the result is higher than the upper limit of the normal range).

If HCV antibody test result is positive, add HCV RNA test (the result is higher than the upper limit of the normal range).

15. known to be allergic to recombinant humanized PD-1 monoclonal antibody drug and its components;

16. known to be allergic to EGFR monoclonal antibody drugs and their components;

17. have active lung disease (interstitial pneumonia, pneumonia, obstructive lung disease, asthma) or a history of active tuberculosis

18. have any uncontrollable clinical problem, including but not limited to: Persistent or active (severe) infection; Poorly medically controlled hypertension (blood pressure greater than 150/90 mmHg persistently).

Poorly controlled diabetes mellitus; Cardiac disease (Class III/IV congestive heart failure or heart block as defined by the New York Heart Association);

19. the following conditions within 6 months prior to the first dose: deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmia or angina; percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft; cerebrovascular accident, transient ischemic attack, cerebral embolism

20. having undergone stem cell transplantation or organ transplantation

21. persons with a history of psychotropic substance abuse that they are unable to abstain from or a history of psychiatric disorders

22. other serious, acute or chronic medical conditions or abnormalities in laboratory tests that, in the judgment of the investigator, may increase the risk associated with participation in the study, or may interfere with the interpretation of study results

23. Patients who, in the judgment of the investigator, have poor compliance or have other conditions that make them unsuitable for participation in the trial.