A Study of Cemiplimab With Chemotherapy and Immunotherapy in People With Head and Neck Cancer
A Study of Cemiplimab With Chemotherapy and Immunotherapy in People With Head and Neck Cancer
The purpose of this study is to find out whether combining the standard chemotherapy for head
 and neck cancer with the immunotherapy drugs cetuximab and cemiplimab (the study drug) is a
 safe treatment for head and neck cancer, and whether receiving this combination treatment
 before surgery may allow participants to forgo the standard radiation treatment after
 surgery.
Inclusion Criteria:

 -  Pathologically (histologically or cytologically) proven diagnosis of squamous cell
 carcinoma of the head and neck that has arisen from the oral cavity, oropharynx, nasal
 cavity, paranasal sinuses, larynx, or hypopharynx

 -  Clinical stage T1, N2-3; T2, N1-3, T3/T4a, Any N (AJCC, 8th ed.) without evidence of
 distant metastasis (M0) based on PET/CT or CT chest, abdomen, and pelvis, for which
 standard-of-care treatment would entail surgical resection with adjuvant radiation +/-
 chemotherapy.

 ° Patients with recurrent and multiple primary head and neck cancers that are
 surgically resectable are eligible if the patient did not receive prior radiation or
 systemic therapy.

 -  Disease must be amenable to surgical resection.

 -  The patient must be a surgical candidate.

 1. Hemoglobin > 9.0 g/dL

 2. Absolute neutrophil count (ANC) >1.5 x 10^9/L

 3. Platelet count >100 x 10^9/L

 4. Serum creatinine <1.5 upper limit of normal (ULN) or estimated creatinine
 clearance (CrCl) >30 mL/min

 5. Adequate hepatic function:

 -  Total bilirubin <1.5 x upper limit of normal ULN)

 -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both < 3 x ULN

 -  Alkaline phosphatase (ALP) <2.5 x ULN Note: For patients with Gilbert syndrome, total
 bilirubin <3x ULN. Upper central must be documented appropriately as past medical
 history.

 -  Men and woman >18 years old

 -  Eastern cooperative oncology group performance status < 1

 Exclusion Criteria:

 -  Prior radiation and systemic therapy for a head and neck cancer.

 -  Oral cavity cancer that is not amenable to surgical resection or the patient is not a
 surgical candidate.

 -  Active or prior documented autoimmune or inflammatory disorders that have been treated
 with steroids or immunomodulator therapy in the past 5 years.

 Exceptions: Patients with vitiligo, type 1 diabetes mellitus, and endocrinopathies
 (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone
 replacement, childhood asthma that is resolved, or psoriasis it does not require systemic
 treatment are permitted.

 -  Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily
 prednisone equivalents) or other immunosuppressant medications within 14 days of
 treatment on study.

 -  Receipt of live attenuated vaccine within 30 days prior initiating treatment on study.

 -  Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.

 -  Any infection requiring hospitalization and/or intravenous antibiotic therapy within 2
 weeks of the start of treatment.

 -  Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or
 hepatitis C virus (HBV or HCV) infection; or diagnosis of immunodeficiency.

 1. Patients with known HIV infection who have controlled infection (undetectable
 viral load (HIV RNA PCR) and CD4 count above 350, either spontaneously or on a
 stable antiviral regimen) are permitted. For patients with controlled HIV
 infection monitoring will be performed per local standards

 2. Patients with HBV (hepatitis B surface antigen positive; HBsAg+) who have
 controlled infection (serum HBV DNA PCR that is below the limit of detection and
 receiving anti-viral therapy for HBV) are permitted. Patients with controlled
 infections must undergo periodic monitoring of HBV DNA. Patients must remain on
 anti-viral therapy for at least 6 months be on the last dose of Cemiplimab.

 3. Patients were HCV antibody positive (HCV Ab+) who have controlled infection
 (undetectable HCV RNA by PCR, either spontaneously or in response to successful
 prior course of anti-HCV therapy) are permitted.

 -  History of immune-related pneumonitis with the last 5 years.

 -  History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing
 pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses
 of leuko-corticoids to assist with management.

 -  Known hypersensitivity or allergy to any of the excipients in the cemiplimab drug
 product.

 -  Patients with a history of solid organ transplant (exception: corneal transplant)

 -  Any medical comorbidity, physical examination finding, or metabolic dysfunction, or
 clinical laboratory abnormality that in the opinion of the investigator renders the
 patient unsuitable for participation in a clinical trial due to high safety risks.

 -  Women with a positive serum or urine beta-hCG pregnancy test at screening/baseline
 visit. If positive, pregnancy must be ruled out by ultrasound for patient to be
 eligible.

 -  Breast-feeding women

 -  Women of childbearing potential who are sexually active and aren't willing to practice
 highly effective contraception prior to the first dose of Cemiplimab, during the
 study, and for at least 180 days after the last dose. Highly effective contraceptive
 measures include:

 1. Stable use of combined estrogen and progesterone containing hormonal
 contraception or progesterone and-only hormonal contraception associated with
 inhibition of ovulation initiated 2 or more menstrual cycles prior to screening

 2. Intrauterine device; intrauterine hormone-releasing system

 3. Bilateral tubal ligation

 4. Vasectomized partner and/or

 5. Sexual abstinence