Cetuximab and Cemiplimab before Surgery for the Treatment of Resectable Head and Neck Squamous Cell Cancer
This phase II trial studies how well the combination of cetuximab and cemiplimab works before surgery in treating patients with head and neck squamous cell cancer that can be removed by surgery (resectable). Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Cemiplimab is a type of drug called an immune checkpoint inhibitor (a type of immunotherapy). It is a monoclonal antibody that binds to the protein PD-1 on the surface of immune cells called T cells. It works by keeping tumor cells from suppressing the immune system. This allows the immune system to attack and kill the tumor cells. Giving the combination of cetuximab and cemiplimab before surgery may make the tumor smaller.
Inclusion Criteria
- Must be ≥ 18 years of age at the time of consent
- Patient (or a legally authorized representative) must understand and voluntarily sign informed consent prior to any study-related assessments/procedures being conducted
- Must be able and willing to comply to the study visit schedule and protocol requirements
- Must have sufficient archived tumor tissue available for PD-L1 combined positive score (CPS) determination. If not, patient must agree to a fresh tumor biopsy before starting the treatments. If patient only had a fine needle aspiration, a fresh biopsy with a core needle or punch biopsy is required
- If the primary site is oropharynx, p16/human papillomavirus (HPV) status must be determined. HPV status determined by cell free HPV DNA testing is also acceptable
- Must have surgically resectable HNSCC including oral cavity, oropharynx, larynx, and hypopharynx. Patients with p16-positive or HPV-positive unknown primary of head and neck are eligible. Must be newly diagnosed HNSCC with T1-2 N1-3 or T3-4 N0-3 undergoing surgery as a standard of care. If the tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base or encases carotid artery, and/or prevertebral fascia involvement, it will be considered as unresectable and excluded
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Absolute neutrophil count (ANC) > 1500/mm^3 * Blood transfusion and/or blood product support are allowed
- Hemoglobin > 9.0 g/dL * Blood transfusion and/or blood product support are allowed
- Platelet count > 100,000/mm^3 * Blood transfusion and/or blood product support are allowed
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal (ULN) * Blood transfusion and/or blood product support are allowed
- Total bilirubin ≤ 1.5 mg/dL * Blood transfusion and/or blood product support are allowed
- Patients with Gilbert's Syndrome must have a total bilirubin ≤ 3.0 mg/dL * Blood transfusion and/or blood product support are allowed
- An estimated creatinine clearance (eCrCl) ≥ 40 mL/min at screening using the Cockcroft-Gault formula * Blood transfusion and/or blood product support are allowed
- Patients of childbearing potential and patients whose sexual partners are of childbearing potential must be willing to practice an approved method of highly effective birth control with their partners starting at the time of informed consent and for 1 year after the completion of the study treatment regimen. Women of childbearing potential must have a negative pregnancy test within the 7 days prior to enrollment
Exclusion Criteria
- Patients with an active autoimmune disease that has required systemic treatment in past 2 years
- Patients with a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Patient with a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab and/or cemiplimab or if the patient had red meat allergy/tick bite history
- Patients with an active infection requiring systemic therapy
- Patients with a known history of human immunodeficiency virus (HIV) infection
- Patients with a known history of or is positive for Hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C (defined as hepatitis C virus [HCV] ribonucleic acid is detected)
- Patients who have a history of a left ventricular ejection fraction (LVEF) of < 45% or who are New York Heart Association (NYHA) class 2 or higher. For asymptomatic patients, echocardiogram is not required
- Patients with cardiovascular disease defined as: * Uncontrolled hypertension defined as blood pressure > 160/90 mmHg at screening confirmed by repeat (medication permitted) * History of torsades de pointes, clinically significant electrocardiogram (ECG) abnormalities, including ventricular rhythm disturbances, unstable cardiac arrhythmia requiring medication, pathologic symptomatic bradycardia, left bundle branch block, second degree atrioventricular (AV) block type II, third degree AV block, grade ≥ 2 bradycardia, uncorrected hypokalemia not amenable to correction, congenital long QT syndrome, prolonged QT interval due to medications, corrected QT (QTc) > 450 msec (for men) or > 470 msec (for women) * Symptomatic heart failure (per New York Heart Association guidelines; (Caraballo, 2019), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction < 20%, transient ischemic attack, or cerebrovascular accident within 12 months of day 1)
- Patients who are of the following protected classes will be excluded: * Pregnant, parturient, or breastfeeding women * Persons who are hospitalized without consent because of a judiciary or administrative decision * Patients with a legal protection measure or a person who cannot express his/her consent * Patients in emergency situations who cannot consent to the study
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06855212.
Locations matching your search criteria
United States
Florida
Tampa
PRIMARY OBJECTIVE:
I. To evaluate the major and complete pathologic response rate of neoadjuvant cetuximab and cemiplimab combination in patients undergoing surgery for head and neck squamous cell cancer (HNSCC).
SECONDARY OBJECTIVES:
I. To evaluate the event free survival (EFS) in patients treated with the neoadjuvant cetuximab and cemiplimab combination before the surgery for HNSCC.
II. To evaluate the tolerability of the neoadjuvant cetuximab and cemiplimab combination before the surgery for HNSCC.
EXPLORATORY OBJECTIVES:
I. To identify potential biomarkers related to T-cell memory response to neoadjuvant cetuximab and cemiplimab combination in patients undergoing surgery for HNSCC.
II. To evaluate biomarkers including neutrophil lymphocyte ratio (NLR), human leukocyte antigen-I loss of heterozygosity (HLA class I LOH), TIM characterization using multiplex immunohistochemistry (mIHC) including PD-L1 expression, detection of minimal residual disease (MRD) using circulating tumor deoxyribonucleic acid (DNA), and gene expression profiling (GEP) to predict tumor response.
OUTLINE:
Patients receive cemiplimab intravenously (IV) on day 1 of each cycle and cetuximab IV on days 1, 8, and 15 of cycle 1 and on day 1 of cycle 2. Cycles repeat every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care (SOC) surgical resection 7-21 days after cycle 2 day 1. Patients also undergo computed tomography (CT) and blood sample collection throughout the trial. Patients may undergo tissue biopsy throughout the study and may undergo magnetic resonance imaging (MRI) and/or positron emission tomography (PET)/CT as clinically indicated.
After completion of study treatment, patients are followed up at 42 days and then 16, 32, 48, and 96 weeks from SOC surgical resection.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMoffitt Cancer Center
Principal InvestigatorChristine H. Chung
- Primary IDMCC-23204
- Secondary IDsNCI-2025-01687
- ClinicalTrials.gov IDNCT06855212