ACTIVE_NOT_RECRUITING

Immunotherapy Combination: Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 for Subjects With Recurrent/Metastatic Gastric or Head and Neck Cancer

Conditions

Gastroesophageal Junction (GEJ) Cancers Advanced HNSCC PD-L1 t-haNK cells GEJ cancer Cellular Therapy Keytruda

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2021-12-14

Study Completion:2027-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04847466

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Gastric/GEJ cancer Cohort: * Participants must have metastatic or unresectable locally advanced Gastric/GEJ cancer that has been histologically confirmed. * Participants must have radiologically evaluable disease, with or without measurable lesions by RECISTv1.1. Evaluable but non-measurable disease include small lesions (longest diameter \<10mm or pathological lymph nodes with \>=10 to \<15mm short axis), ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly identified by physical exam that is not measurable by reproducible imaging techniques. * Participants must have received or been ineligible to receive first line systemic chemotherapy for Gastric/GEJ cancer. Participants with HER2 positive disease must have received HER2-targeted therapy. * Head and neck squamous cell carcinoma Cohort * Participants must have metastatic or unresectable locally advanced HNSCC that has been histologically confirmed. * 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). * Age \>=18 years. Because no dosing or adverse event data are currently available on the use of this investigation combination therapy in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. * ECOG performance status \<2 (Karnofsky \>60%) * Participants must have adequate organ and marrow function as defined below: * leukocytes \>=3,000/mcL * absolute neutrophil count \>=1,500/mcL * platelets \>=100,000/mcL * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) \<=2.5 X institutional upper limit of normal * creatinine Creatinine within 1.5X upper limit of normal institutional limits * Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. * Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first 7 weeks of therapy. * Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Participants on therapeutic anticoagulation with warfarin must have an international normalized ratio (INR) that is within target range for their condition at the time of enrollment. * The effects of PD-L1 t-haNKs with N-803 and pembrolizumab on the developing human fetus are unknown. For this reason and because these investigational agents teratogenicity is unknown, individuals of child-bearing potential and individuals who can father a child must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation and for at least 4 months after last dose of study drug pembrolizumab. * Ability of subject to understand and the willingness to sign a written informed consent document.	* Participants who are receiving any other investigational agents or concurrent anticancer treatment. Palliative radiotherapy is allowed. * Participants with concurrent use of systemic steroids (within 10 days of enrollment), except for physiologic doses of systemic steroid replacement or local (topical, nasal, intraarticular or inhaled) steroid use. * Participants with active systemic autoimmune disease (e.g., lupus erythematosus, rheumatoid arthritis, Addison s disease, autoimmune disease associated with lymphoma, inflammatory bowel disease). Participants with autoimmune endocrine disorders controlled with medical management (e.g. thyroid disorders, type 1 diabetes, or adrenal insufficiency) will not be excluded * Participants with a history of grade 3 or higher immune-related adverse events attributed to pembrolizumab or other anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. This exclusion does not apply to participants with permanent endocrine insufficiencies (e.g. adrenal insufficiency or hypothyroidism) under satisfactory medical management. Additionally, participants with grade 2 adverse events attributed to these classes of agents will be excluded with the exception of rash, transient hyperthyroidism, transient liver enzyme abnormalities or other transient events that resolved without steroids or immunomodulatory agents. * HIV or HBV infection due to unknown effect of PD-L1 targeting via a CAR or N-803 in these chronic viral infections. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled serious cardiac arrhythmia, clinically significant coagulopathy or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant individuals are excluded from this study because PD-L1 targeting via a CAR has unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PD-L1 targeting via a CAR and N-803, nursing should be discontinued if the mother is treated on this study for the duration of study participation and for at least 4 months after last dose of any study drug.

Inclusion Criteria

Exclusion Criteria

* Gastric/GEJ cancer Cohort:
* Participants must have metastatic or unresectable locally advanced Gastric/GEJ cancer that has been histologically confirmed.
* Participants must have radiologically evaluable disease, with or without measurable lesions by RECISTv1.1. Evaluable but non-measurable disease include small lesions (longest diameter \<10mm or pathological lymph nodes with \>=10 to \<15mm short axis), ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly identified by physical exam that is not measurable by reproducible imaging techniques.
* Participants must have received or been ineligible to receive first line systemic chemotherapy for Gastric/GEJ cancer. Participants with HER2 positive disease must have received HER2-targeted therapy.
* Head and neck squamous cell carcinoma Cohort
* Participants must have metastatic or unresectable locally advanced HNSCC that has been histologically confirmed.
* 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).
* Age \>=18 years. Because no dosing or adverse event data are currently available on the use of this investigation combination therapy in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
* ECOG performance status \<2 (Karnofsky \>60%)
* Participants must have adequate organ and marrow function as defined below:
* leukocytes \>=3,000/mcL
* absolute neutrophil count \>=1,500/mcL
* platelets \>=100,000/mcL
* total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) \<=2.5 X institutional upper limit of normal
* creatinine Creatinine within 1.5X upper limit of normal institutional limits
* Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
* Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first 7 weeks of therapy.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Participants on therapeutic anticoagulation with warfarin must have an international normalized ratio (INR) that is within target range for their condition at the time of enrollment.
* The effects of PD-L1 t-haNKs with N-803 and pembrolizumab on the developing human fetus are unknown. For this reason and because these investigational agents teratogenicity is unknown, individuals of child-bearing potential and individuals who can father a child must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation and for at least 4 months after last dose of study drug pembrolizumab.
* Ability of subject to understand and the willingness to sign a written informed consent document.

* Participants who are receiving any other investigational agents or concurrent anticancer treatment. Palliative radiotherapy is allowed.
* Participants with concurrent use of systemic steroids (within 10 days of enrollment), except for physiologic doses of systemic steroid replacement or local (topical, nasal, intraarticular or inhaled) steroid use.
* Participants with active systemic autoimmune disease (e.g., lupus erythematosus, rheumatoid arthritis, Addison s disease, autoimmune disease associated with lymphoma, inflammatory bowel disease). Participants with autoimmune endocrine disorders controlled with medical management (e.g. thyroid disorders, type 1 diabetes, or adrenal insufficiency) will not be excluded
* Participants with a history of grade 3 or higher immune-related adverse events attributed to pembrolizumab or other anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. This exclusion does not apply to participants with permanent endocrine insufficiencies (e.g. adrenal insufficiency or hypothyroidism) under satisfactory medical management. Additionally, participants with grade 2 adverse events attributed to these classes of agents will be excluded with the exception of rash, transient hyperthyroidism, transient liver enzyme abnormalities or other transient events that resolved without steroids or immunomodulatory agents.
* HIV or HBV infection due to unknown effect of PD-L1 targeting via a CAR or N-803 in these chronic viral infections.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled serious cardiac arrhythmia, clinically significant coagulopathy or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant individuals are excluded from this study because PD-L1 targeting via a CAR has unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PD-L1 targeting via a CAR and N-803, nursing should be discontinued if the mother is treated on this study for the duration of study participation and for at least 4 months after last dose of any study drug.

Contacts and Locations

Principal Investigator

Charalampos Floudas, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Charalampos Floudas, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-12-14

Study Completion Date2027-12-31

Study Record Updates

Study Start Date2021-12-14

Study Completion Date2027-12-31

Terms related to this study

Keywords Provided by Researchers

PD-L1 t-haNK cells
GEJ cancer
Advanced HNSCC
Cellular Therapy
Keytruda

Additional Relevant MeSH Terms

Gastroesophageal Junction (GEJ) Cancers
Advanced HNSCC