CIML NK Cells and Nogapendekin Alfa Alone or in Combination with Ipilimumab and With or Without Cetuximab for the Treatment of Recurrent or Metastatic Head and Neck Cancer

Inclusion Criteria

• Histologically or cytologically confirmed, recurrent or metastatic squamous cell carcinoma of the head neck (including oral cavity, oropharynx, larynx, hypopharynx, paranasal sinuses) or salivary gland carcinoma (including adenoid cystic carcinoma and non-adenoid cystic carcinoma histologies)
• Any human papillomavirus (HPV) status or smoking history is permitted. Oropharyngeal cancer patients are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV polymerase chain reaction (PCR) or in-situ hybridization (ISH) testing
• Available haploidentical donor that is willing and eligible for non-mobilized collection
• Prior exposure to a platinum-containing regimen (either in the definitive or advanced, recurrent/metastatic setting) and exposure to a PD-1/L1 inhibitor is required for the squamous cell carcinoma of the head and neck (SCCHN) patients only
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• No systemic corticosteroid therapy (=< 10 mg of prednisone or equivalent dose of systemic steroids for non-autoimmune indications for at least 2 weeks prior to NK cell infusion)
• Ability to understand and the willingness to sign a written informed consent document
• Negative pregnancy test for women of childbearing potential only. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours before the start of ipilimumab
• The effects of CIML NK cells and N-803 on the developing human fetus are unknown. For this reason, WOCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for up to 26 weeks after the last dose of all investigational products (up to 16 weeks after the last N-803 dose), in such a manner that the risk of pregnancy is minimized. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Willing to provide blood and tissue from diagnostic biopsy and at the time of surgery
• Leukocytes >= 2,500/mcL
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 90,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
• Oxygen saturation: >= 90% on room air
• Left ventricular ejection fraction (cardiac function) > 40%
• No laboratory evidence of ongoing hemolysis in opinion of investigator

Exclusion Criteria

• Patients with nasopharyngeal carcinoma are not eligible
• Participants who have had anti-tumor chemotherapy or other investigational agents within 2 weeks prior to cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 3 weeks prior, or those who have not recovered from adverse events due to agents administered more than 3 weeks prior
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to N-803 or other agents used in study
• Solid organ transplant (allograft) recipients
• Participants who are receiving any other investigational agents
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [Wegener’s granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis). Patients with Hashimoto thyroiditis are eligible
• 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 study requirements
• Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and N-803 and with the potential for teratogenic or abortifacient effects by fludarabine/cyclophosphamide chemotherapy regimen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and N-803, breastfeeding should be discontinued if the mother is treated on this study
• Human immunodeficiency virus (HIV)-positive participants are ineligible because of the potential for pharmacokinetic interactions with anti-retroviral agents used in this study. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy
• Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high-risk of lethal treatment-related hepatotoxicity in the setting of marrow suppression
• Known non-infectious pneumonitis or any history of interstitial lung disease
• Receipt of a live vaccine within 30 days of start of study treatment
• Prior history of grade 2 or higher hemolytic anemia ( >= 2g decrease in hemoglobin plus laboratory evidence of hemolysis) from any cause