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

NCT06161545 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001564001564-C
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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 IV Squamous Cell Carcinoma of the Head and Neck; Stage II Squamous Cell Carcinoma of the Head and Neck; Stage III Squamous Cell Carcinoma of the Head and Neck

Keywords

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

Outcome Measures

Primary Outcomes (1)

• pTR rate (viable tumor in 50% or less of the surgically resected primary tumor bed)

  Digital pathology software assessment of H and E slides from the surgical specimen. The fraction of participants on each arm who experience a pathologic tumor response (pTR) will be reported along with a 95% confidence interval.

  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.

Secondary Outcomes (4)

• Safety

  90 days after surgery

• Recurrence free survival

  2 years

• Overall survival

  2 years

• Median time from diagnosis to definitive surgery

  time of surgery

Study Arms (2)

Arm 1

EXPERIMENTAL

N-803 + pembrolizumab

Drug: pembrolizumab; Drug: N-803

Arm 2

EXPERIMENTAL

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

Biological: PD-L1 t-haNK cells; Drug: pembrolizumab; Drug: N-803

Interventions

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

Arm 2

pembrolizumab DRUG

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

Arm 1; Arm 2

N-803 DRUG

15 ug/kg via subcutaneous injection on Day 1

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; ALT-803

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Charalampos Floudas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI Medical Oncology Referral Office

CONTACT

(240) 760-6050; ncimo_referrals@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2023
• First Posted: December 8, 2023
• Study Start: September 24, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 8, 2026

Record last verified: 2025-10-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: This study will comply with the NIH Data Management and Sharing (DMS) Policy. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Data from this study may be requested by contacting the PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)