A Phase II Sequential Window of Opportunity Trial of Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma
Background: Squamous cell carcinoma is a type of cancer that can cause tumors on the head and neck (HNSCC). Even with treatment, less than 50% of people with certain types of HNSCC survive for 5 years.
Objective: To test a new drug treatment (N-803 and pembrolizumab, with or without PD-L1 t-haNK cells) in people with HNSCC. These drugs may help the immune system to fight cancer.
Eligibility: People aged 18 years and older who have HNSCC that is not linked to human papillomavirus infection. They must not yet have received any treatment and be scheduled for surgery to remove the tumors.
Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and a test of their heart function. They will have a biopsy: A sample of tissue will be removed from the tumor. Pembrolizumab is given through a tube attached to a needle inserted into a vein in the arm (intravenous infusion). N-803 is injected under the skin of the abdomen. All participants will receive these 2 treatments on day 1. They will have follow-up visits on days 8 and 15. Some participants will also receive PD-L1 t-haNK cells by intravenous infusion. These are cells that attack cancer cells. These participants will receive this treatment on days 1, 5, 8, 12, and 15. All participants will have a clinic visit on day 21. They will have a second biopsy. Follow-up visits will occur on days 49 and 105. Visits will continue by phone or email every 9 weeks for 2 years....
• Histologically or cytologically confirmed previously untreated intermediate/high risk, p16-negative (if oropharyngeal primary tumor), squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV). Note: p16 status will be determined by a history of p16 immunohistochemistry (IHC) staining conducted per standard of care.
• Age \>= 18 years.
• ECOG performance status \<= 1.
• Planned for cancer removal surgery per standard of care.
• Participants must have adequate organ and marrow function as defined below:
‣ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 3.0 x upper limit of normal (ULN)
⁃ Total bilirubin \<= 1 x ULN. Note: Participants with Gilbert's syndrome can have total bilirubin \< 3.0 mg/dL
⁃ Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
⁃ Hemoglobin (Hgb) \>= 10.0 g/dL
⁃ Platelet count \>= 100 x 10\^9/L
⁃ Prothrombin time (PT) and partial thromboplastin time (PTT) \<= 1 x ULN. Note: Participants with prolonged PTT determined to be due to lupus anticoagulant are eligible
⁃ Creatinine \<= 1.5 x ULN
• Participants with a history of human immunodeficiency virus (HIV) infection must:
‣ be on effective anti-retroviral therapy; and
⁃ have the viral load \< 400 copies/mL; and
⁃ have the CD4 count \> 150 cells/microL
• Participants with a history of Hepatitis C virus (HCV) infection must
‣ received curative treatment; and
⁃ have an undetectable viral load.
• Individuals of child-bearing potential (IOCBP) and those who can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device (IUD), surgical sterilization) for the duration of the study treatment and up to 4 months after the last dose of the study drug (s).
• Nursing participants must be willing to discontinue nursing from study treatment initiation through 4 months after the last dose of the study drug(s).
• Participants must have a primary tumor site that is amenable to biopsy and be willing to undergo pre-and post-treatment biopsies.
• The ability of a participant to understand and the willingness to sign a written informed consent document.