Pembrolizumab plus N-803, with or without PD-L1 t‑haNK cells, for operable HPV‑negative head and neck cancer
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
This trial will test whether giving N‑803 with pembrolizumab, and in some patients adding PD‑L1 t‑haNK immune cells before surgery, can improve outcomes for people with HPV‑negative resectable head and neck squamous cell carcinoma.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 18 Years to 120 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | prednisone, pembrolizumab, chemotherapy |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT06161545 on ClinicalTrials.gov |
What this trial studies
This Phase 2 neoadjuvant trial enrolls adults with previously untreated, p16/HPV‑negative resectable head and neck squamous cell carcinoma who are scheduled for curative surgery. Participants receive pembrolizumab intravenously and N‑803 subcutaneously prior to their planned surgery, and a subset will also receive PD‑L1 t‑haNK cell infusions. Clinical exams, blood and urine tests, imaging, cardiac evaluation, and tumor biopsies are collected before and after treatment to measure safety, immune changes, and signals of anti-tumor activity. The approach builds on prior neoadjuvant PD‑1 work and explores whether adding an IL‑15 agonist and engineered NK cells can overcome mechanisms that make some tumors resistant to T cell killing.
Who should consider this trial
Good fit: Adults (age ≥18) with previously untreated, resectable, p16/HPV‑negative stage II–IV head and neck squamous cell carcinoma who are surgical candidates with ECOG ≤1 and adequate organ function are the intended participants.
Not a fit: Patients with HPV‑positive tumors, prior treatment for their cancer, poor performance status, inadequate organ function, or those not eligible for surgery are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could strengthen anti-tumor immune responses and lower the risk of cancer recurrence after surgery.
How similar studies have performed: Neoadjuvant PD‑1 blockade has shown improved recurrence-free survival in several trials for resectable HNSCC and combining IL‑15 agonists with PD‑1 inhibitors has supportive preclinical and early clinical rationale, while adding PD‑L1 t‑haNK cells is a more novel component.
Eligibility criteria
Show full inclusion / exclusion criteria
* 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.
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Charalampos Floudas, M.D. — National Cancer Institute (NCI)
- Study coordinator: NCI Medical Oncology Referral Office
- Email: ncimo_referrals@nih.gov
- Phone: (240) 760-6050
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.