CAR T Cells for Mesothelioma

Overseen By Raffit Hassan, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic corticosteroids

Disqualifiers: Autoimmune disease, Immunodeficiency, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating mesothelioma, a challenging cancer affecting the lining of certain organs. The treatment uses a patient's own T cells, modified in a lab to target and destroy cancer cells displaying a specific protein called mesothelin (MSLN). This modified cell therapy is known as TNhYP218 CAR T Cells. Ideal participants have mesothelioma or other solid tumors that produce this protein and have not responded to standard treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain treatments like systemic therapy, investigational therapy, or radiation within 14 to 21 days before starting the trial, and you must not be on therapeutic doses of systemic corticosteroids within 14 days before treatment.

Is there any evidence suggesting that TNhYP218 CAR T cells are likely to be safe for humans?

Previous studies have shown that TNhYP218 CAR T cells effectively target and destroy tumors with high levels of mesothelin, a protein linked to mesothelioma. Research indicates that these cells may remain in the body longer, potentially increasing their effectiveness. This treatment resembles other CAR T-cell therapies that have successfully treated blood cancers.

However, CAR T-cell therapies can sometimes cause side effects, such as flu-like symptoms, low blood counts, or cytokine release syndrome, which can lead to fever and low blood pressure. As this is an early-stage trial, the main goal is to ensure the treatment's safety and determine the appropriate dose.

This trial is in its first phase, meaning the treatment is still being tested for safety. While specific safety data for TNhYP218 CAR T cells is not yet available, the early stage of the trial means researchers are closely monitoring how well participants tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for mesothelioma, which often include surgery, chemotherapy, and radiation, TNhYP218 CAR T cells offer a novel approach by harnessing the body's immune system to specifically target cancer cells. Most treatments work by directly attacking the tumor itself, but TNhYP218 CAR T cells are engineered to recognize and destroy mesothelin-expressing tumor cells, which could lead to more precise targeting and fewer side effects. Researchers are excited because this method has the potential to provide a more personalized and effective treatment, marking a significant advancement in the fight against mesothelioma.

What evidence suggests that TNhYP218 CAR T cells might be an effective treatment for mesothelioma?

Research has shown that TNhYP218 CAR T cells, which are specially altered immune cells, could effectively treat mesothelioma tumors. This trial includes two treatment arms: a dose escalation arm and a dose expansion arm. Participants in the dose escalation arm will receive TNhYP218 CAR T cells at increasing doses, while those in the dose expansion arm will receive the recommended phase 2 dose determined in the first arm. Studies have found that these cells excel at attacking tumors with high levels of mesothelin, a protein often present in mesothelioma. In early tests, these CAR T cells effectively killed tumors and remained active in the body for extended periods. This prolonged activity suggests they might outperform past treatments against mesothelioma. While CAR T-cell therapies have mostly been used for blood cancers, these results are promising for solid tumors like mesothelioma. ^{1 2 3 4 6}

Who Is on the Research Team?

Raffit Hassan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with solid tumors, including mesothelioma, that have not responded to standard treatments. Participants must have enough of a protein called MSLN in their tumors and will undergo procedures like leukapheresis and biopsies.

Inclusion Criteria

Ability of participant to understand and the willingness to sign a written informed consent document.

Participant must have at least 1 measurable lesion by RECIST version 1.1.

My side effects from previous treatments are mild.

Exclusion Criteria

Participants with any form of primary immunodeficiency (e.g. severe combined immunodeficiency).

History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.

I do not have any ongoing illnesses that could affect my safety or participation in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis and Cell Manufacturing

Participants undergo leukapheresis to collect T cells, which are then modified in a lab to produce TNhYP218 CAR T cells

2-3 weeks

1 visit (in-person)

Lymphodepletion and Treatment

Participants receive lymphodepletion with chemotherapeutic drugs followed by infusion of TNhYP218 CAR T cells

2 weeks

Daily visits during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular visits including imaging scans, blood and heart tests, and biopsies

Long-term Follow-up

Long-term safety monitoring for up to 15 years as per FDA requirement

10 years

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• TNhYP218 CAR T Cells

Trial Overview The study tests TNhYP218 CAR T cells, which are the participant's own immune cells modified to attack tumor cells with high levels of MSLN. It includes pre-treatment drugs, infusion of the CAR T cells, and extensive follow-up visits for up to 15 years.

How Is the Trial Designed?

Group I: 2/Dose Expansion Experimental Treatment 4 Interventions

Participants with mesothelioma will undergo lymphodepletion and will receive TNhYP218 CAR T cells at the RP2D determined in Arm 1

Group II: 1/Dose Escalation Experimental Treatment 4 Interventions

Participants with mesothelin expressing tumors will undergo lymphodepletion and will receive TNhYP218 CAR T cells at escalating doses

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

CAR T-cell therapy, which involves engineering a patient's T cells to target cancer cells, has shown impressive success in treating leukemia and lymphoma, particularly with the CD19 target.

Research is ongoing to adapt CAR T-cell therapy for solid tumors like lung cancer and esophageal cancer, but there are significant challenges that need to be addressed to improve its effectiveness in these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor (CAR) T-Cell Therapy for Thoracic Malignancies. Kiesgen, S., Chicaybam, L., Chintala, NK., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06885697

Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T ... We hypothesize that TNaive/SCM anti-mesothelin, TNhYP218 CAR T cells will have enhanced anti-tumor activity and increased persistence in participants with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9256778/

Development of Highly Effective Anti-Mesothelin hYP218 ... Our results show that hYP218 CAR T cells, targeting mesothelin epitope close to cell membrane, are very effective against mesothelin-positive tumors.

3. asbestos.com asbestos.com/news/2025/07/22/clinical-trial-to-test-new-mesothelioma-car-t-cell-immunotherapy/

CAR T-Cell Therapy Trial Launches for Mesothelioma ... While CAR T-cell therapies have shown success in treating blood cancers, they have struggled to work against solid tumors like mesothelioma.

4. trialx.com trialx.com/clinical-trials/listings/299277/anti-mesothelin-tnaivescm-hyp218-tnhyp218-car-t-cells-in-participants-with-mesothelin-expressing-solid-tumors-including-mesothelioma/

Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T ... hYP218 CAR T cells target membrane-proximal region of mesothelin and in pre-clinical studies have shown increased tumor killing and persistence ...

5. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/5567/701352/Abstract-5567-hYP218-CAR-T-cells-targeting-a

Abstract 5567: hYP218 CAR-T cells targeting a membrane ... Increased accumulation of hYP218 CAR-T cells in the tumor may explain their increased efficacy. These results support its clinical development ...

6. mesothelioma.net mesothelioma.net/chimeric-antigen-receptor-car-t-cell-clinical-trial/

CAR T-Cell Clinical Trials for Mesothelioma Anti-Mesothelin TNaive/​SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma.