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

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

Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma (NCT06161545) is a Phase 2 interventional studying Stage II Squamous Cell Carcinoma of the Head and Neck and Stage III Squamous Cell Carcinoma of the Head and Neck, sponsored by National Cancer Institute (NCI). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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....

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Stage II Squamous Cell Carcinoma of the Head and Neck and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 40 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

* Who May Qualify: - diagnosed by tissue sample (biopsy-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 weakened immune system 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). ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

* 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. * 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. EXCLUSION CRITERIA: * 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.

Treatments Being Tested

BIOLOGICAL

PD-L1 t-haNK cells

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

DRUG

pembrolizumab

400 mg administered as a 30 minute IV infusion on Day 1

DRUG

N-803

15 ug/kg via subcutaneous injection on Day 1

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06161545), the sponsor (National Cancer Institute (NCI)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06161545 clinical trial studying?

Who can participate in NCT06161545?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06161545?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06161545. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06161545. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.