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....
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.
Participant must have progressed on at least one FDA-approved systemic therapy considered standard of care for their tumor type. There is no limit on the number of prior treatment regimens. Note: Given the aggressive nature of pancreatic cancer, otherwise eligible individuals with this cancer type can undergo leukapheresis before or while they are getting their frontline treatment as long as they meet all other inclusion criteria. However, TNhYP218 CAR T cells will only be administered after progression on first line standard of care therapy.
Participant must have at least 1 measurable lesion by RECIST version 1.1.
Tumor must have MSLN positivity of 2+ to 3+ in >= 50% cancer cells by immunohistochemistry on freshly collected biopsy or archival tissue.
Prior systemic therapy, an investigational therapy, radiation, and/or surgery within 14 days prior to leukapheresis and 21 days prior to lymphodepleting chemotherapy.
Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation.
Participants with any form of primary immunodeficiency (e.g. severe combined immunodeficiency).
Participants with active or history of autoimmune or immune mediated disease such as multiple sclerosis, lupus, inflammatory bowel disease, rheumatoid arthritis, or small vessel vasculitis. NOTE: Participants with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
National Cancer Institute (NCI)
Lead sponsor