RecruitingPhase 2NCT06161545

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


Sponsor

National Cancer Institute (NCI)

Enrollment

40 participants

Start Date

Sep 24, 2025

Study Type

INTERVENTIONAL

Conditions

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....


Eligibility

Min Age: 18 YearsMax Age: 120 Years

Plain Language Summary

Simplified for easier understanding

This study tests combinations of immunotherapy drugs — pembrolizumab, N-803 (an immune activator), and targeted therapy (PD-L1 t-haNK cells) — in people with advanced cancers that have not responded to prior PD-1/PD-L1 immunotherapy. The goal is to re-engage the immune system to fight the cancer. **You may be eligible if...** - You are 18 or older with a solid tumor cancer that has progressed on prior anti-PD-1/PD-L1 therapy - Your cancer is measurable on imaging - Your general health score is 0–1 (ECOG), meaning you can carry out normal activities - Your organ function is within acceptable ranges **You may NOT be eligible if...** - You have active autoimmune disease requiring systemic treatment - You have active or untreated brain metastases - You have serious infections, HIV, or active hepatitis - You are pregnant or breastfeeding - You have had organ transplant or are on immunosuppressive therapy Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BIOLOGICALPD-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

DRUGpembrolizumab

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

DRUGN-803

15 ug/kg via subcutaneous injection on Day 1


Locations(1)

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

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NCT06161545