Phase 1 Study With Dose Expansion of the Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma
National Cancer Institute (NCI)
Summary
Background: Mesothelioma is an aggressive cancer that grows in the linings of the body; this can include the membranes that line the heart, lungs, and internal organs. Mesothelin (MSLN) is a protein that appears in high numbers in many tumors, including mesothelioma. Researchers are developing a new treatment that collects a person s own immune cells (T cells); the T cells are genetically modified to target and kill tumor cells with high levels of MSLN. Objective: To test a new treatment (TNhYP218 CAR T cells) in people with solid tumors including mesothelioma. Eligibility: People aged 18 and older with solid tumors including mesothelioma that returned or spread after standard treatment. Design: Participants will be screened. A small piece of tissue will be cut from a tumor (biopsy). The sample will be tested to see if it has enough MSLN. Participants will undergo leukapheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein. Participant s T cells will be modified in a lab to produce TNhYP218 CAR T cells. Participants will enter the hospital. For 7 days, they will receive drugs to prepare their bodies for the study treatment. TNhYP218 CAR T cells will be administered into a vein. Participants will remain in the hospital for at least 7 more days. After discharge, participants will have follow-up visits for 5 years. These visits may include imaging scans, blood and heart tests, and a new biopsy. Long-term follow-up will continue another 10 years.
Description
Background: * Mesothelin (MSLN), a cell surface glycoprotein, normally expressed on the mesothelial cells lining the pleura, peritoneum, and pericardium, is highly expressed in many cancers including mesothelioma, ovarian, lung, thymic, colorectal, pancreatic, and gastric cancers, making it an attractive target for immunotherapy. * Adoptive cell therapy using CAR T cells exploits the ability of these modified T cells to recognize and kill their target. Several mesothelin directed CAR T cell therapies have been evaluated in clinical trials, but thus far have not resulted in significant anti-tu…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria. For this protocol, treatment initiation is defined as the first day of lymphodepleting chemotherapy. * Participant must have unresectable, locally advanced, or metastatic, or recurrent mesothelioma and other mesothelin expressing solid tumors. For participants with mesothelioma only those with epithelioid or biphasic histology (with \>80% epithelioid component) will be eligible. The diagnosis will be confirmed by the Laboratory of Pathology, CCR, NCI. * Participa…
Interventions
- Devicemesothelin expression testing
Assay done at screening to determine mesothelin expression levels
- BiologicalTNhYP217 CAR T Cells
Variable doses, administered intravenously on Day 0
- Drugfludarabine
30 mg/m\^2 IV infusion administered followed by cyclophosphamide on days both are given. Daily x 4 doses on Day -7, -6, -5 and -4
- Drugcyclophosphamide
600 mg/m\^2 IV infusion. Daily x 3 doses on Day -6, -5, -4
Location
- National Institutes of Health Clinical CenterBethesda, Maryland