Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma
- Conditions
- Stage IV Squamous Cell Carcinoma of the Head and NeckStage II Squamous Cell Carcinoma of the Head and NeckStage III Squamous Cell Carcinoma of the Head and Neck
- Interventions
- Registration Number
- NCT06161545
- Lead Sponsor
- National Cancer Institute (NCI)
- 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....
- Detailed Description
Background:
* Even in the potentially curative setting, human papillomavirus (HPV)-unrelated head and neck squamous cell carcinomas (HNSCC) are associated with dismal outcomes (compared to HPV-related) despite maximal surgical and adjuvant treatment (i.e., radiotherapy +/-chemotherapy).
* The window period between diagnosis and curative surgery provides a window of opportunity to administer therapies that may improve outcomes.
* Four published clinical trials suggest that neoadjuvant checkpoint blockade can improve recurrence-free survival (RFS) in resectable HNSCC (NCT02919683, NCT02488759, NCT02296684, NCT04247282). This includes NCI protocol 20C0024 (NCT04247282) where in addition to demonstrating improved 1-year RFS compared to historical values, our correlative studies provided insight into potential mechanisms of this benefit.
* N-803 (an IL-15 agonist) combined with anti-programmed cell death protein 1 (PD-1) therapies work toward maximization of T cell-mediated anti-tumor activity, a key component of anti-tumor immunity. However, expression of T cell inhibitory receptors and/or loss of antigen presentation and processing machinery, often driven by T cell activity s release of interferon-gamma renders some tumor cells invulnerable to T cell killing.
* Studies conducted by collaborators at the NCI have shown that programmed death-ligand (PD-L1) t-haNK can lyse such T-cell-resistant tumor cells. Additionally, in a murine model of oral cancer, the triplet of PD-L1 t-haNK combined with pembrolizumab and N-803 resulted in more tumor control than the doublet combinations of these agents.
* PD-L1 t-haNK cells is an allogenic, irradiated (no engraftment), off-the-shelf cell line currently being studied in combination with pembrolizumab and N-803 in advanced/metastatic HNSCC (NCI CCR protocol 000096, (NCT04847466)). As of November 2022, 10 participants have been treated and the regimen has been well tolerated.
* In addition to potentially improving outcomes, testing this triplet in the neoadjuvant setting with pre-and post-treatment tumor biopsies provides an opportunity to gain insight into the mechanisms of this regimen s anti-tumor activity.
Objective
-To determine the pathologic tumor response (pTR) rate (viable tumor in 50% or less of the surgically resected primary tumor bed) in Arm 1 and Arm 2.
Eligibility 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.
* Age \>= 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 and adequate organ function.
Design
* This is an open-label, single-site, non-randomized, phase II study to evaluate the efficacy of combined treatment of PD-L1 t-haNK cells, pembrolizumab, and N-803.
* The first 15 participants will be enrolled in Arm 1 and treated with pembrolizumab and N-803, the following participants will be enrolled in Arm 2 and treated with pembrolizumab, N-803, and PD-L1 t-haNK cells.
* All participants (Arm 1 and Arm 2) will receive treatment consisting of one intravenous (IV) infusion of pembrolizumab and one subcutaneous (SC) injection of N-803 on Day 1.
* Participants in Arm 2 will receive additional treatment with IV infusion of PD-L1 t-haNK cells on Days 1, 5, 8, 12, and 15.
* Participants will be monitored for 2 years.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 2 PD-L1 t-haNK cells N-803 + pembrolizumab + PD-L1 t-haNK cells Arm 2 pembrolizumab N-803 + pembrolizumab + PD-L1 t-haNK cells Arm 1 N-803 N-803 + pembrolizumab Arm 2 N-803 N-803 + pembrolizumab + PD-L1 t-haNK cells Arm 1 pembrolizumab N-803 + pembrolizumab
- Primary Outcome Measures
Name Time Method pTR rate (viable tumor in 50% or less of the surgically resected primary tumor bed) 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. 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.
- Secondary Outcome Measures
Name Time Method Median time from diagnosis to definitive surgery time of surgery Record the date of diagnosis and date of definitive surgery.
Time from diagnosis to definitive surgery time of surgery Record the date of diagnosis and date of definitive surgery.
Overall survival 1 and 2 years After treatment, contact the participant on days 49, 105 and every 9 weeks until death or 2 years after treatment initiation. Determined on each arm separately using a Kaplan-Meier curve. The one-year and two-year OS and RFS will be determined and reported on each arm along with a 95% confidence interval.
Recurrence free survival 1 and 2 years CT scans of chest and neck with contrast. Determined on each arm separately using a Kaplan-Meier curve. The one-year and two-year OS and RFS will be determined and reported on each arm along with a 95% confidence interval.
Safety Days 1-105 Arm 1: Any toxicities identified on Days 1, 15, 21, on Days 49 and 105 Safety Follow Up visits which occurs 105 (+14) days after the study agent(s) was/were last administered. Beyond 105 days after the last intervention, only adverse events which are serious and related to the study intervention need to be recorded at each follow up visit (every 9 weeks) until participants are off study.Arm 2: Any toxicities identified on Days 1, 5, 8, 12, 15, 21, on Days 49 and 105 Safety Follow Up visits which occurs 105 (+14) days after the study agent(s) was/were last administered. Beyond 105 days after the last intervention, only adverse events which are serious and related to the study intervention need to be recorded at each follow up visit (every 9 weeks) until participants are off study.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States