Actively Recruiting
Phase 1 Study With Dose Expansion of Anti-Mesothelin TNhYP218 CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma
Led by National Cancer Institute (NCI) · Updated on 2026-06-05
100
Participants Needed
1
Research Sites
521 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new treatment called TNhYP218 CAR T cells for people with solid tumors, including mesothelioma, which is a fast-growing cancer affecting the linings of organs such as the lungs and heart. This treatment uses a person's own immune cells, which are modified in a lab to better target and attack tumor cells that have high levels of a protein called mesothelin. The study is a phase 1 trial aiming to find the right dose and observe early responses in participants with mesothelioma and other tumors expressing mesothelin. Participants will have their tumor tissue tested for mesothelin levels through a biopsy. Blood is collected to isolate T cells, which are then genetically changed to create TNhYP218 CAR T cells. Before receiving the modified cells, participants undergo chemotherapy to prepare the body. The TNhYP218 CAR T cells are given through a vein, and patients stay in the hospital for about two weeks during treatment and initial monitoring. The study includes a dose escalation phase and a dose expansion phase for mesothelioma patients at the recommended dose. During the study, participants will have regular follow-up visits for up to 5 years, including imaging scans, blood tests, heart exams, and possible additional biopsies to monitor response and safety. Long-term monitoring for an additional 10 years will assess ongoing safety and treatment effects. The main goals are to find a safe dose, evaluate early tumor response by imaging, and track side effects and overall health over time.
CONDITIONS
Brief Title
Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Diagnosis of unresectable, locally advanced, metastatic, or recurrent mesothelioma or other mesothelin-expressing solid tumors
- For mesothelioma, only epithelioid or biphasic histology with greater than 80% epithelioid component
- Progression after at least one FDA-approved standard systemic therapy
- At least one measurable lesion by RECIST version 1.1
- Tumor shows mesothelin positivity (2+ to 3+) in 50% or more cancer cells
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ and marrow function as defined by specified laboratory values
- Normal cardiac ejection fraction (≥ 45%) and no significant pericardial effusion
- Room air oxygen saturation of 90% or greater
- Resolved prior treatment-related toxicities to grade 2 or less
- Stable, treated central nervous system metastases with no recent corticosteroid or antiseizure medication use
- Agreement to use contraception or abstinence if of childbearing potential
- Willingness to discontinue nursing during treatment and follow-up
- Ability to understand and sign informed consent
You will not qualify if you...
- Prior systemic therapy, investigational therapy, radiation, or surgery within 14 days before leukapheresis and 21 days before lymphodepleting chemotherapy
- Prior use of anti-PD-1, anti-PD-L1, or agents affecting immune activity within 8 weeks before treatment
- Primary immunodeficiency disorders
- Active or history of autoimmune or immune-mediated diseases excluding certain controlled conditions
- Severe immediate hypersensitivity to cyclophosphamide or fludarabine
- Use of therapeutic systemic corticosteroids within 14 days before treatment initiation
- Lung fibrosis, inflammatory lung disease, or pneumonitis
- Other prior or concurrent malignancies except for specified treated cancers
- Electrocardiogram QTc interval above specified thresholds
- Active infections with HIV, hepatitis B or C, or HTLV
- Pregnancy or intention to become pregnant during required contraception period
- Receipt of live or virus-based vaccines within 30 days before treatment
- History of seizure disorder unless due to treated metastatic lesions
- Uncontrolled intercurrent illness or active infection impacting safety or compliance
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) for mesothelin expression testing and eligibility assessment
Duration - 4 days
Participants receive chemotherapy with fludarabine and cyclophosphamide to prepare for CAR T cell infusion.
Daily visits for 4 days for chemotherapy infusion
Duration - Single day infusion on Day 0
Participants receive an infusion of TNhYP218 CAR T cells targeting mesothelin-expressing tumors.
1 visit (in-person) for CAR T cell infusion
Duration - Up to 24 weeks
Participants are closely monitored for safety and adverse events following CAR T cell infusion.
Daily visits from Day 0 to Day 4, visits on Day 7, Day 10, Day 21, every 2 weeks from Week 4 to Week 8, then every 4 weeks through Week 24
Duration - Up to 15 years
Participants are followed for long-term safety and outcomes including survival for up to 15 years after treatment.
Visits at baseline, Weeks 4, 12, 24, 48, and annually thereafter if needed
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
M
Maria Gracia L Agra, R.N.
R
Raffit Hassan, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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