RECRUITING

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

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

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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....

Official Title

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

Quick Facts

Study Start:2025-07-18

Study Completion:2028-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06161545

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

NCI Medical Oncology Referral Office

CONTACT

(240) 760-6050

ncimo_referrals@nih.gov

Principal Investigator

Charalampos Floudas, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Charalampos Floudas, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-18

Study Completion Date2028-12-01

Study Record Updates

Study Start Date2025-07-18

Study Completion Date2028-12-01

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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