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 undergo surgery
* Patients who have stage III-IV disease without distant metastases (M0) of 1) oral cavity, 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 disease without distant metastases (M0) using AJCC 8th edition
* All patients with oropharyngeal SCCHN must be tested for HPV (by p16 and/or HPV in situ hybridization \[ISH\] or polymerase chain reaction \[PCR\])
* Patients must be evaluated by a head and neck surgeon and be deemed surgically resectable 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 subjects with Gilbert syndrome, who can have total bilirubin \< 3 mg/dl)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x the upper limit of normal
* Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or serum creatinine less than or equal to 1.5 x upper limit of 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 to avoid pregnancy for 23 weeks after the last dose of study drugs; "women of reproductive potential" 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 of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year; men who are receiving the study medications will be instructed to adhere to contraception for 31 weeks after the last dose of study drugs; men who are azoospermic 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 device within 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 other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
* 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 cervical cancer that has undergone potentially curative therapy; patients with a history of other prior malignancy must have been treated with curative intent and must have remained 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 (excludes emergency transient steroid use at discretion of the treating physician).
* Patients that have an active autoimmune disease requiring systemic treatment within the 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, or resolved childhood asthma/atopy would be an exception to this rule. Inhaled or topical steroids, and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
* Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B surface 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 lung disease
* Patients who have received a live vaccine within 30 days prior initiation of the systemic regimen
* Patients must not be receiving any other investigational agents
* Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial
* Women must not be pregnant (as above) or breastfeeding