This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug to learn whether the drug works in treating a
specific disease. "Investigational" means that the drug or combination of interventions is
Nivolumab is approved by the U.S. Food and Drug Administration (FDA) for the treatment of
recurrent or advanced head and neck cancer (head and neck cancer that has come back or is
incurable) but is considered investigational for head and neck cancer patients who have not
received prior chemotherapy.
- Subject must have histologically or cytologically confirmed, resectable or
unresectable, Stage III or Stage IV locoregionally advanced squamous cell carcinoma of
the larynx or hypopharynx, as defined by 2017 American Joint Committee on Cancer
(AJCC), 8th edition
- Willing to provide tissue from diagnostic biopsy and blood samples before, during, and
- Any smoking history is permitted
- Patients must have HPV negative disease. Those patients with a supraglottic primary
are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory
HPV PCR or ISH testing to rule out oropharyngeal origin with laryngeal extension
- Age 18 years or older
- ECOG performance status ≤ 1 (Karnofsky ≥ 80%, see Appendix A)
- Participant must have normal organ and marrow function as defined below within 21 days
prior to study registration:
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin ≤2.0 g/dL
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine within normal institutional limits OR
- creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal
- Ability to understand and the willingness to sign a written informed consent document
- Women of childbearing potential (WOCBP) must agree to use appropriate method(s) of
contraception. WOCBP should plan to use an adequate method to avoid pregnancy for 5
months (30 days plus the time required for nivolumab to undergo five half-lives) after
the last dose of investigational drug
- Women of childbearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 iu/l or equivalent units of hcg) within 24 hours prior to the
start of nivolumab
- Women of childbearing potential (WOCBP)" is defined as any female who has experienced
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral
oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12
months of amenorrhea in a woman over 45 in the absence of other biological or
physiological causes. In addition, women under the age of 55 must have a documented
serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
- Men who are sexually active with WOCBP must agree to use any contraceptive method with
a failure rate of less than 1% per year. Men who are sexually active with WOCBP will
be instructed to adhere to contraception for a period of 7 months after the last dose
of investigational product. Women who are not of childbearing potential (ie, who are
postmenopausal or surgically sterile as well as azoospermic men) do not require
- Existing severe autoimmune conditions (at the discretion of the treating physician).
Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone
therapy are not excluded. Short-term corticosteroid dosing is permitted (i.e.
dexamethasone for chemotherapy-induced nausea prevention during induction
chemotherapy) as long as steroids are discontinued within 1 week (7 days) of receiving
the first dose of nivolumab during the induction phase of treatment.
- Subject who has had prior chemotherapy for head and neck cancer and/or radiotherapy to
the head and neck.
- Subject who has been treated with immunotherapy. This includes prior treatment with
anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or immune checkpoint pathways.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
- Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency. Any
positive test result for hepatitis B virus or hepatitis C virus indicating presence of
virus, e.g., Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or
Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).
- Known non-infectious pneumonitis or any history of interstitial lung disease.
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer, and
low-risk prostate adenocarcinoma being managed with active surveillance. A history of
another separate malignancy in remission without evidence of active disease in the
last 5 years is permitted.