Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to 120 Years
• SexAll
• Healthy volunteersNo

You may be able to join if

• INCLUSION CRITERIA:
• 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.
• Women of child-bearing potential (WOCBP) must agree to use a highly effective method of contraception (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).
• Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 4 months after the last dose of the study drug (s). A participant may request a female partner to use an effective form of contraception to fulfill this requirement. Men must not freeze or donate sperm within the same period.
• 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.

You cannot join if

• History of allergic reactions attributed to compounds of similar chemical or biological composition to drugs used in the study.
• Active immunosuppressive treatment equivalent of > 10mg of prednisone daily. Note: Short-course systemic corticosteroids (e.g., prevention/treatment for transfusion reaction) or use for a non-cancer indication (e.g., adrenal replacement) is acceptable.
• History of autoimmune disease with the exception of controlled thyroid disease, psoriasis not requiring medications, vitiligo, and alopecia.
• Participants with a history of hepatitis B (HBV).
• Prior malignancy active within the previous 2 years except for locally curable cancer that is currently considered cured and does not require an additional standard of care treatment, such as cutaneous basal or squamous cell carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental histological finding of prostate cancer.
• Prior therapy with the investigational drug within 2 weeks prior to the treatment initiation.
• Pregnancy (confirmed with Beta-human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test performed in individuals of childbearing potential at screening).
• Uncontrolled intercurrent illness or medical condition(s) evaluated by medical history and physical exam or situations that are not stable (e.g., recent hospitalization, Emergency Room visit or undergoing medication changes) that the investigator assesses would unacceptably increase of participation in the trial for the participant or impair the ability to evaluate the endpoints of the study.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Treatments listed in the registry

• PD-L1 t-haNK cells (Biological): Irradiated PD-L1 t-haNK cells at a dose of 2 x 10^9 administered via IV infusion over 30 minutes on Days 1, 5, 8, 12, and 15
• pembrolizumab (Drug): 400 mg administered as a 30 minute IV infusion on Day 1
• N-803 (Drug): 15 ug/kg via subcutaneous injection on Day 1

Non Randomized · Sequential · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• surgery: Part of the study plan
• radiation: Part of the study plan

Main goals

• pTR rate (viable tumor in 50% or less of the surgically resected primary tumor bed) (From enrollment to 5 days after the last infusion of PD-L1 t-hank cells or at least 20 days after pembrolizumab/N-803 administration.)

Other goals

• Safety
• Recurrence free survival
• Overall survival
• Median time from diagnosis to definitive surgery

Planned enrollment: 40 (estimated).

• National Institutes of Health Clinical Center, Bethesda, Maryland

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06161545

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 17, 2026. Public record; not medical advice.