Ignite Creation Date:
2024-05-06 @ 7:52 PM
Last Modification Date:
2024-10-26 @ 3:15 PM
Study NCT ID:
NCT06161545
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2023-12-04
Brief Title:
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
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 ie 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 andor 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 advancedmetastatic 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 intermediatehigh 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
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 ie 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 andor 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 advancedmetastatic 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 intermediatehigh 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001564-C | None | None | None |