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

NCT04847466 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10000096000096-C
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastroesophageal Junction (GEJ) Cancers; Advanced HNSCC

Keywords

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

Outcome Measures

Primary Outcomes (1)

• To determine the clinical response rate (CR+PR) with irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab in patients with head and neck squamous cell carcinoma and gastric/GEJ cancer.

  Clinical response rate (CR+PR)

  every 6 weeks

Secondary Outcomes (3)

• To assess the progression free survival (PFS) in patients with HNSCC and/or gastric/GEJ cancer treated with irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab

  Until progression or death

• To assess the safety and tolerability of irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab in patients with head and neck squamous cell carcinoma and/or gastric/GEJ cancer

  28 days after treatment (Study Calendar-Last AE evaluation)

• To assess duration of response in patients with HNSCC and/or gastric/GEJ cancer treated with irradiated PD-L1 CAR-NK cells in combination with N-803 plus pembrolizumab

  Until progression or death

Study Arms (1)

1/Arm 1

EXPERIMENTAL

1-week lead in for PD-L1 CAR NK cell monotherapy followed by combination therapy of Pembrolizumab plus N-803

Drug: N-803; Drug: Pembrolizumab; Biological: PD-L1 t-haNK

Interventions

N-803 DRUG

N-803 will be given via subcutaneous injection at a dose of 15 mcg/kg every 4 weeks (1 week after starting treatment with the PDL-1 CAR-NK cells).

1/Arm 1

Pembrolizumab DRUG

Pembrolizumab 400 mg will be administered as a 30-minute IV infusion every 6 weeks. Pembrolizumab will be administered on the same day as the PD-L1 CAR-NK cells.

1/Arm 1

PD-L1 t-haNK BIOLOGICAL

PD-L1 CAR NK cells (2x109) will be administered by IV infusion over approximately 30 minutes every week. After the week 6 treatment, these cells will be given every 2 weeks.

1/Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neoplasms

Interventions

ALT-803; pembrolizumab

Study Officials

• Charalampos Floudas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2021
• First Posted: April 19, 2021
• Study Start: December 14, 2021
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 8, 2026

Record last verified: 2025-12-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)