A Phase II Clinical Trial of Anti-EGFR Antibody-drug Conjugate (ADC) Combined With or Without Immune Checkpoint Inhibitors in the Neoadjuvant Treatment of Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

A Randomized, Non-comparative, Multicenter Phase II Clinical Trial of Becotatug Vedotin Combined With or Without Immune Checkpoint Inhibitors (Penpulimab/Ivonescimab) in the Neoadjuvant Treatment of Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

A Randomized, Non-comparative, Multicenter Phase II Clinical Trial of Becotatug Vedotin Combined with or without Immune Checkpoint Inhibitors (Penpulimab/Ivonescimab) in the Neoadjuvant Treatment of Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma (LAHNSCC). This proposed study will evaluate the efficacy and safety of preoperative administration of Becotatug Vedotin Combined with or without Immune Checkpoint Inhibitors (Penpulimab/Ivonescimab) in LAHNSCC who are eligible for resection.

In this study, eligible patients will be randomized in a 1:1:1 ratio to either the Becotatug Vedotin treatment group (Cohort 1), or the Becotatug Vedotin combined with Penpulimab treatment group (Cohort 2), or the Becotatug Vedotin combined with Ivonescimab treatment group (Cohort 3). Pathological response rate will be the primary outcome measures. Adverse events will also be recorded.

Inclusion Criteria:

1. Age: 18 - 70 years old, gender not restricted;
2. Histopathologically diagnosed as squamous cell carcinoma of the head and neck (including oral cancer, laryngeal cancer, hypopharyngeal cancer, and oropharyngeal cancer, etc.);
3. Patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC);
4. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1;
5. Have not received any treatment for head and neck squamous cell carcinoma before, including drug treatment, radiotherapy, surgical treatment, etc.;
6. No distant metastasis;
7. The patient has the intention for radical treatment;
8. Good hematopoietic function (total white blood cell count ≥ 3.0×109 /L, absolute lymphocyte count ≥ 0.8×109/L, absolute neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109 /L, hemoglobin ≥ 90g/L) and no blood transfusion or biological response modifiers (such as granulocyte growth factors, erythropoietin growth factors, etc.) treatment within 14 days before the first administration;
9. Good liver function (total bilirubin (TBIL) ≤ 1.5×ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 2.5×ULN; serum albumin ≥ 28 g/L);
10. Good renal function (serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance rate ≥ 50 mL/min (Cockcroft-Gault formula), urine protein less than 2+, or 24-hour urine protein quantification < 1g);
11. Good cardiac function, that is, normal electrocardiogram or abnormal without clinical significance, and echocardiography shows left ventricular ejection fraction (left ventricular ejection fraction, LVEF) ≥ 50%;
12. Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN, if the subject is receiving anticoagulation treatment, as long as the PT is within the range of the anticoagulant drug plan, it is acceptable;
13. During the screening period, blood pressure is well controlled (defined as systolic blood pressure ≤ 150 mmHg and diastolic blood pressure ≤ 90 mmHg), and there is no change in antihypertensive treatment within 1 week before the first administration of the study drug;
14. Patients with HBV infection who can detect HBV deoxyribonucleic acid (DNA) levels (≥ 10IU/mL or above the detection limit) must receive antiviral treatment before randomization according to the clinical institution practice to ensure adequate viral suppression. Patients must maintain antiviral treatment during the study and within 6 months after the last study treatment administration. Patients with positive Anti-HBc detection but no HBV DNA ( < 10IU/mL or below the detection limit) do not require antiviral treatment, unless HBV DNA exceeds 10IU/mL or above the detection limit during the treatment period;
15. Male patients with fertility and women of childbearing age who are willing to take effective contraceptive measures from signing the informed consent form to the last administration of the study drug within 6 months; women of childbearing age include pre-menopausal women and post-menopausal women within 1 year. The blood pregnancy test result of women of childbearing age within ≤ 7 days before the first administration of the study drug must be negative;
16. The subject voluntarily joins the study, signs the informed consent form, has good compliance, and cooperates with follow-up.

Exclusion Criteria:

1. Has received any form of anti-tumor treatment before;
2. Patients with allergic constitution and congenital immune deficiency;
3. Has undergone organ transplantation before;
4. Has a history of severe bleeding tendency or coagulation dysfunction; had significant clinical bleeding symptoms within 1 month before the study treatment, including but not limited to gastrointestinal bleeding and hemoptysis; had continuous anticoagulation treatment within 10 days before the study treatment;
5. Has experienced thromboembolic events such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 6 months before the study treatment;
6. Has active autoimmune or inflammatory diseases, or has a related history, including inflammatory bowel disease (such as colitis or Crohn's disease), diverticulitis (except diverticular disease), systemic lupus erythematosus, sarcoidosis syndrome or Wegener's syndrome (such as granulomatous vasculitis, Gray's disease, rheumatoid arthritis, pituitary inflammation and uveitis). There are the following exceptions: patients with vitiligo or alopecia; patients with stable hypothyroidism after hormone replacement therapy (such as after Hashimoto's thyroiditis); any patients with chronic skin diseases that do not require systemic treatment; patients who can be included within the past 5 years without active diseases, but only after consultation with the study doctor;
7. Active infections, including tuberculosis or human immunodeficiency virus (HIV 1/2 antibody positive);
8. Uncontrolled complications, including but not limited to: receiving study treatment for persistent or active infections (except HBV or HCV), symptomatic congestive heart failure, uncontrolled diabetes, uncontrolled hypertension, unstable angina pectoris, uncontrolled arrhythmia, active interstitial lung disease, severe chronic gastrointestinal diseases with diarrhea, or conditions that may limit compliance with study requirements, increase the risk of adverse events or affect the subject's ability to provide written informed consent;
9. Pregnant or lactating women;
10. The patient does not agree to use effective contraceptive measures during the treatment period and within the following 3 months;
11. Patients participating in other clinical studies simultaneously;
12. Patients with critical conditions unable to complete the survey;
13. Other primary malignant tumor history, but the following situations are excluded: malignant tumors treated for curative purposes, and having no known active diseases for ≥ 5 years before the study treatment and a low potential risk of recurrence; fully treated non-melanoma skin cancer or benign lentigo-like nevus without evidence of disease; fully treated carcinoma in situ with no evidence of disease;
14. Patients with a history of mental illness (such as schizophrenia, mania, anxiety disorder, depression, phobia, etc.) or patients diagnosed with mental illness during the clinical trial enrollment or their spouses;
15. Patients with communication disorders due to confusion, aphasia, or intellectual disability caused by reasons such as communication barriers or inability to answer normally;
16. Patients with other malignant tumor diseases;
17. Has a ≥ 3-grade allergy history to any component of vebecotota monoclonal antibody and/or pannipil monoclonal antibody injection and/or ivosizumab monoclonal antibody injection;
18. The investigator considers that there are other factors that are not suitable for inclusion or that may affect the subject's participation or completion of the study.