Ignite Creation Date:
2025-12-24 @ 4:01 PM
Ignite Modification Date:
2025-12-27 @ 9:31 AM
Study NCT ID:
NCT04847466
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-24
First Post:
2021-04-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Immunotherapy Combination: Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 for Subjects With Recurrent/Metastatic Gastric or Head and Neck Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase II Study of Immunotherapy Combination: Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 for Subjects With Recurrent/Metastatic Gastric or Head and Neck Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-12-12
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:
Immunotherapy is a powerful tool in the fight against cancer. It uses the body s own immune system to fight the cancer. Unfortunately, cancer cells can find ways to escape from destruction by the body s immune system, even when immunotherapy is used.
Natural killer (NK) cells are an important part of the body s immune system and can help fight cancer. In combination with immunotherapy, researchers are using engineered NK cells that recognize and kill cancer cells trying to escape destruction by the immune system.
Objective:
To test the effectiveness of irradiated PD-L1 CAR-NK cells, combined with pembrolizumab and N-803, in people with advanced forms of gastric or head and neck cancer.
Eligibility:
Adults ages 18 and older with advanced gastric or head and neck cancer who have already had standard cancer treatment.
Design:
Participants will be screened with a medical history and physical exam. Their symptoms and ability to do normal activities will be assessed. They will have blood and urine tests. They will have imaging scans of the chest, abdomen, and pelvis.
Participants will get PD-L1 CAR-NK cells by intravenous (IV) infusion. They will get the cells once a week for 6 weeks. Then they will get the cells once every 2 weeks. Before each infusion, an IV catheter will be placed in a large arm vein for infusion of these treatments.
Participants will get pembrolizumab by IV every 6 weeks. They will get N-803 under the skin every 4 weeks.
Participants will get the study drugs for up to 2 years. They will have study visits every 1-2 weeks during treatment. They will have a safety visit 28 days after treatment ends.
After treatment ends, participants will be contacted for follow-up every 2 months for a year. Then they will be contacted every 6 months. They will have tumor scans every 6-12 weeks until their cancer gets worse.
Immunotherapy is a powerful tool in the fight against cancer. It uses the body s own immune system to fight the cancer. Unfortunately, cancer cells can find ways to escape from destruction by the body s immune system, even when immunotherapy is used.
Natural killer (NK) cells are an important part of the body s immune system and can help fight cancer. In combination with immunotherapy, researchers are using engineered NK cells that recognize and kill cancer cells trying to escape destruction by the immune system.
Objective:
To test the effectiveness of irradiated PD-L1 CAR-NK cells, combined with pembrolizumab and N-803, in people with advanced forms of gastric or head and neck cancer.
Eligibility:
Adults ages 18 and older with advanced gastric or head and neck cancer who have already had standard cancer treatment.
Design:
Participants will be screened with a medical history and physical exam. Their symptoms and ability to do normal activities will be assessed. They will have blood and urine tests. They will have imaging scans of the chest, abdomen, and pelvis.
Participants will get PD-L1 CAR-NK cells by intravenous (IV) infusion. They will get the cells once a week for 6 weeks. Then they will get the cells once every 2 weeks. Before each infusion, an IV catheter will be placed in a large arm vein for infusion of these treatments.
Participants will get pembrolizumab by IV every 6 weeks. They will get N-803 under the skin every 4 weeks.
Participants will get the study drugs for up to 2 years. They will have study visits every 1-2 weeks during treatment. They will have a safety visit 28 days after treatment ends.
After treatment ends, participants will be contacted for follow-up every 2 months for a year. Then they will be contacted every 6 months. They will have tumor scans every 6-12 weeks until their cancer gets worse.
Detailed Description:
Background:
* Natural killer (NK) cells are an important component of an anti-tumor immune response.
* PD-L1 CAR-NK (PD-L1 t-haNKs) is an off the shelf, irradiated human, allogeneic, NK cell line that is frozen, shipped, thawed and then infused.
* PD-L1 CAR-NK cells have been engineered to have 3 adaptive modifications:
* Expression of a chimeric antigen receptor (CAR) targeting the tumor-associated antigen PD-L1
* Expression of the high-affinity variant (158V) of the human Fc gamma receptor (Fc gamma RIIIa/CD16a)
* An endoplasmic reticulum-retained version of the human interleukin-2 (ERIL-2) cytokine.
* To improve the safety profile, PD-L1 CAR-NK cells are irradiated, thus inhibiting proliferation while maintaining cytotoxicity.
* Irradiated PD-L1 CAR-NK cells are highly effective at lysing PD-L1 expressing tumor cells as well as PD-L1 null tumor cells (via expression of native NK cell receptors).
* Preliminary clinical data from 10 participants treated with PD-L1 CAR-NK cells (NCT04050709) suggest PD-L1 CAR-NK are well tolerated at a dose of 2x10\^9 cells intravenous (IV) twice per week. An additional 8 participants have received irradiated PDL1 CAR-NK under single patient INDs. PD-L1 CAR-NK cell treatment combined with PD-1 blockade and cytokine therapy may synergistically activate the T-cell and NK cell arms of the immune system and enhance anti-tumor activity.
* The combination of N-803 + PD-1/PD-L1 interaction blockade has a manageable safety profile
Objectives:
* Determine the 6-month progression free survival with irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab in participants with gastric/GEJ cancer.
* Determine the clinical response rate (CR+PR) with irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab in participants with Head and neck squamous cell carcinoma.
Eligibility:
* Gastric/GEJ cancer Cohort
* Participants must have metastatic or unresectable locally advanced Gastric/GEJ cancer.
* Participants must have evaluable disease with or without measurable disease by RECISTv1.1.
* Participants must have completed, had disease progression on, or been ineligible to receive first-line systemic chemotherapy for advanced/metastatic disease and anti-PD-1 therapy for advanced/metastatic disease.
* Participants with HER2 positive disease must have received HER2-targeted systemic therapy.
* Head and neck squamous cell carcinoma Cohort
* Participants must have metastatic or unresectable locally advanced HNSCC.
* Participants must have measurable disease by RECISTv1.1. If the participant is one of the first six participants enrolled on study and is part of the safety-lead in, either measurable or evaluable (e.g., ascites, elevated tumor marker, or lesion visualized on imaging) disease will be permitted.
* Participants must have received or been ineligible to receive first-line systemic chemotherapy and must have received systemic anti-PD-1 therapy (in the first-line or subsequent-line setting).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Age \>= 18 years
Design:
* This is an open label, single center, phase II trial using a safety lead-in to assess the safety and tolerability of irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab in participants with head and neck squamous cell carcinoma and/or gastric/GEJ cancer.
* The phase II objectives of this study is to assess 6-month progression free survival (PFS) and clinical response rate (CR+PR) in participants with gastric/GEJ cancer and head and neck squamous cell carcinoma, respectively.
* Participants will enroll and receive 1 dose of PD-L1 CAR-NK cell monotherapy (week -1) for PK/PD studies before starting the combined treatment of Pembrolizumab and N-803 one week later (week 0). PD-L1 CAR-NK cells (2x10\^9) will be given intravenously every week until week 6 and then every two weeks from 6 week onward.
* The accrual is 50 evaluable participants. To allow for a small number of inevaluable participants, the accrual ceiling will be set at 55 participants.
* Natural killer (NK) cells are an important component of an anti-tumor immune response.
* PD-L1 CAR-NK (PD-L1 t-haNKs) is an off the shelf, irradiated human, allogeneic, NK cell line that is frozen, shipped, thawed and then infused.
* PD-L1 CAR-NK cells have been engineered to have 3 adaptive modifications:
* Expression of a chimeric antigen receptor (CAR) targeting the tumor-associated antigen PD-L1
* Expression of the high-affinity variant (158V) of the human Fc gamma receptor (Fc gamma RIIIa/CD16a)
* An endoplasmic reticulum-retained version of the human interleukin-2 (ERIL-2) cytokine.
* To improve the safety profile, PD-L1 CAR-NK cells are irradiated, thus inhibiting proliferation while maintaining cytotoxicity.
* Irradiated PD-L1 CAR-NK cells are highly effective at lysing PD-L1 expressing tumor cells as well as PD-L1 null tumor cells (via expression of native NK cell receptors).
* Preliminary clinical data from 10 participants treated with PD-L1 CAR-NK cells (NCT04050709) suggest PD-L1 CAR-NK are well tolerated at a dose of 2x10\^9 cells intravenous (IV) twice per week. An additional 8 participants have received irradiated PDL1 CAR-NK under single patient INDs. PD-L1 CAR-NK cell treatment combined with PD-1 blockade and cytokine therapy may synergistically activate the T-cell and NK cell arms of the immune system and enhance anti-tumor activity.
* The combination of N-803 + PD-1/PD-L1 interaction blockade has a manageable safety profile
Objectives:
* Determine the 6-month progression free survival with irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab in participants with gastric/GEJ cancer.
* Determine the clinical response rate (CR+PR) with irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab in participants with Head and neck squamous cell carcinoma.
Eligibility:
* Gastric/GEJ cancer Cohort
* Participants must have metastatic or unresectable locally advanced Gastric/GEJ cancer.
* Participants must have evaluable disease with or without measurable disease by RECISTv1.1.
* Participants must have completed, had disease progression on, or been ineligible to receive first-line systemic chemotherapy for advanced/metastatic disease and anti-PD-1 therapy for advanced/metastatic disease.
* Participants with HER2 positive disease must have received HER2-targeted systemic therapy.
* Head and neck squamous cell carcinoma Cohort
* Participants must have metastatic or unresectable locally advanced HNSCC.
* Participants must have measurable disease by RECISTv1.1. If the participant is one of the first six participants enrolled on study and is part of the safety-lead in, either measurable or evaluable (e.g., ascites, elevated tumor marker, or lesion visualized on imaging) disease will be permitted.
* Participants must have received or been ineligible to receive first-line systemic chemotherapy and must have received systemic anti-PD-1 therapy (in the first-line or subsequent-line setting).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Age \>= 18 years
Design:
* This is an open label, single center, phase II trial using a safety lead-in to assess the safety and tolerability of irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab in participants with head and neck squamous cell carcinoma and/or gastric/GEJ cancer.
* The phase II objectives of this study is to assess 6-month progression free survival (PFS) and clinical response rate (CR+PR) in participants with gastric/GEJ cancer and head and neck squamous cell carcinoma, respectively.
* Participants will enroll and receive 1 dose of PD-L1 CAR-NK cell monotherapy (week -1) for PK/PD studies before starting the combined treatment of Pembrolizumab and N-803 one week later (week 0). PD-L1 CAR-NK cells (2x10\^9) will be given intravenously every week until week 6 and then every two weeks from 6 week onward.
* The accrual is 50 evaluable participants. To allow for a small number of inevaluable participants, the accrual ceiling will be set at 55 participants.
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 000096-C | None | None | View |