Recruiting
Phase 2

N-803 & Pembrolizumab

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06161545

Conditions

Stage II Squamous Cell Carcinoma of the Head and Neck

Stage III Squamous Cell Carcinoma of the Head and Neck

Stage IV Squamous Cell Carcinoma of the Head and Neck

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

PD-L1 t-haNK cells

pembrolizumab

N-803

Study Details

Brief summary:

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....

Conditions

Stage II Squamous Cell Carcinoma of the Head and Neck

Stage III Squamous Cell Carcinoma of the Head and Neck

Stage IV Squamous Cell Carcinoma of the Head and Neck

Study ID

NCT06161545

Start date

Sep 24, 2025

Status verified date

Aug 20, 2026

Completion date

Dec 1, 2028

Anticipated

Primary completion date

Dec 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • 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.

Study Design

Enrollment

40 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1

N-803 + pembrolizumab

experimental: Arm 2

N-803 + pembrolizumab + PD-L1 t-haNK cells

Interventions

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

pembrolizumab

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

N-803

15 ug/kg via subcutaneous injection on Day 1

Primary outcome measure

  • pTR rate (viable tumor in 50% or less of the surgically resected primary tumor bed) [ Time Frame: 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. ]

Central Contacts and Locations

Central contacts

NCI Medical Oncology Referral Office

(240) 760-6050ncimo_referrals@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

National Cancer Institute Referral Office

888-624-1937

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 24, 2026

Last verified

Aug 20, 2026

Keywords

  • Anti PD-1
  • ALT-803
  • triplet
  • p-16 negative
  • HPV negative

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-24.