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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment TNhYP218 CAR T Cells for mesothelioma?

Research shows that CAR T cell therapy targeting mesothelin, a protein found in high levels in mesothelioma, can slow tumor growth in animal models and is considered relatively safe in clinical trials. However, its effectiveness is still being improved due to challenges like the tumor environment that suppresses the immune response. ^{1 2 3 4 5}

Is CAR T cell therapy safe for treating mesothelioma?

Clinical trials using CAR T cells for mesothelioma have shown that this treatment is relatively safe, with no significant toxicity reported in studies. However, the effectiveness of the treatment is still being improved, and ongoing research is addressing challenges like the tumor environment that can limit the therapy's success. ^{1 2 6 7 8}

How is the TNhYP218 CAR T Cells treatment different from other treatments for mesothelioma?

The TNhYP218 CAR T Cells treatment is unique because it uses genetically engineered T cells to specifically target and attack mesothelioma cells by recognizing a protein called mesothelin, which is commonly found on these cancer cells but not on healthy cells. This approach is different from traditional treatments like chemotherapy, as it aims to harness the body's immune system to fight the cancer more precisely. ^{1 2 3 4 7}

Research Team

Raffit Hassan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Mesothelin-targeted second generation CAR-T cells inhibit growth of mesothelin-expressing tumors in vivo. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Anti-Mesothelin CAR T cell therapy for malignant mesothelioma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Current Advances in CAR T Cell Therapy for Malignant Mesothelioma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Aberrant Lck Signal via CD28 Costimulation Augments Antigen-Specific Functionality and Tumor Control by Redirected T Cells with PD-1 Blockade in Humanized Mice. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor (CAR) T-Cell Therapy for Thoracic Malignancies. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

New Immunotherapy Combinations Enter the Battlefield of Malignant Mesothelioma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

CAR T-cell immunotherapy of MET-expressing malignant mesothelioma. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells. [2021]