Nivolumab, Carboplatin, and Paclitaxel in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma That Can Be Removed by Surgery

Inclusion Criteria:

• Patients must be 18 years of age and older.

• Pathologically confirmed SCCHN, not previously treated, with a plan to undergosurgery

• Patients who have stage III-IV disease without distant metastases (M0) of 1) oralcavity, 2) larynx, 3) hypopharynx 4) oropharynx (human papillomavirus [HPV] neg)using American Joint Committee on Cancer (AJCC) 8th edition

• Patients who have oropharyngeal cancer that HPV positive, stage II-III diseasewithout distant metastases (M0) using AJCC 8th edition

• All patients with oropharyngeal SCCHN must be tested for HPV (by p16 and/or HPV insitu hybridization [ISH] or polymerase chain reaction [PCR])

• Patients must be evaluated by a head and neck surgeon and be deemed surgicallyresectable at baseline

• Tumor sample must be available for HPV p16 and PD-L1 testing and if oropharyngeal,must be tested for HPV p16

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• While blood cells 2000/ul or more

• Absolute neutrophil count 1500/ul or more

• Platelets 100,000/ul or more

• Hemoglobin 9 g/dl or more; (transfusion permitted)

• Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjectswith Gilbert syndrome, who can have total bilirubin < 3 mg/dl)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than orequal to 3 x the upper limit of normal

• Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using theCockcroft-Gault formula or serum creatinine less than or equal to 1.5 x upper limitof normal (ULN)

• Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 21 days of study enrollment

• Women of reproductive potential must use highly effective contraception methods toavoid pregnancy for 23 weeks after the last dose of study drugs; "women ofreproductive potential" is defined as any female who has experienced menarche andwho has not undergone surgical sterilization (hysterectomy or bilateraloophorectomy) or who is not postmenopausal; menopause is defined clinically as 12months of amenorrhea in a woman over 45 in the absence of other biological orphysiological causes; in addition, women under the age of 55 must have a documentedserum follicle stimulating hormone (FSH) level less than 40 mIU/mL

• Men of reproductive potential who are sexually active with women of reproductivepotential must use any contraceptive method with a failure rate of less than 1% peryear; men who are receiving the study medications will be instructed to adhere tocontraception for 31 weeks after the last dose of study drugs; men who areazoospermic do not require contraception

• All subjects must be able to comprehend and sign a written informed consent document

Exclusion Criteria:

• Primary nasopharyngeal carcinoma

• Patients who have participated in a study with an investigational agent or devicewithin 2 weeks of initiation of treatment

• Any prior radiotherapy to the neck

• Any prior treatment for SCCHN

• Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any otherantibody or drug specifically targeting T-cell co-stimulation or immune checkpointpathways

• Any history of a sever hypersensitivity reaction to any monoclonal antibody

• Any history of allergy to the study drug components

• Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin,squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervicalcancer that has undergone potentially curative therapy; patients with a history ofother prior malignancy must have been treated with curative intent and must haveremained disease-free for 3 years post-diagnosis

• Any diagnosis of immunodeficiency or current immunosuppressive therapy including >10mg/day of prednisone within 14 days of enrollment is not permitted (excludesemergency transient steroid use at discretion of the treating physician).

• Patients that have an active autoimmune disease requiring systemic treatment withinthe past 3 months or a documented history of clinically severe autoimmune disease,or a syndrome that requires systemic steroids (> 10 mg daily prednisone equivalents)or immunosuppressive agents. Subjects with vitiligo, type I diabetes mellitus, orresolved childhood asthma/atopy would be an exception to this rule. Inhaled ortopical steroids, and adrenal replacement steroid doses ≤10 mg daily prednisoneequivalent, are permitted in the absence of active autoimmune disease. Subjects withhypothyroidism stable on hormone replacement or Sjorgen's syndrome will not beexcluded from the study.

• Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) oracquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis Bsurface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV]ribonucleic acid [RNA] [qualitative] is detected)

• Patients with evidence of non-infectious pneumonitis or history of interstitial lungdisease

• Patients who have received a live vaccine within 30 days prior initiation of thesystemic regimen

• Patients must not be receiving any other investigational agents

• Patients with uncontrolled intercurrent illnesses including, but not limited to anactive infection requiring systemic therapy or a known psychiatric or substanceabuse disorder(s) that would interfere with cooperation with the requirements of thetrial

• Women must not be pregnant (as above) or breastfeeding