CAR T-cell Therapy for Mesothelioma

Overseen By Adam Schoenfeld, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticonvulsants, Corticosteroids, Immunosuppressives, others

Disqualifiers: Active malignancy, CNS metastases, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

14 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that chemotherapy, targeted therapy, or radiotherapy be stopped at least 7 days before a procedure called leukapheresis, and at least 14 days before receiving T cells. Immunotherapy with CPI must be stopped at least 42 days before receiving T cells. If you're on these treatments, you will need to stop them for a certain period before participating.

What data supports the effectiveness of the treatment MSLN-targeted CAR T-cell Therapy for Mesothelioma?

Research shows that MSLN-targeted CAR T-cell therapy has been safe in initial trials for mesothelioma, and similar therapies have shown promise in slowing tumor growth in other cancers like pancreatic cancer. However, the effectiveness in mesothelioma is still being improved with strategies to enhance the therapy's ability to reach and persist in tumors. ^{1 2 3 4 5}

Is CAR T-cell therapy targeting mesothelin safe for humans?

Clinical trials have shown that mesothelin-targeted CAR T-cell therapy is generally safe, but there have been rare cases of severe lung-related side effects, especially at high doses. It's important for patients with lung conditions to be cautious and discuss potential risks with their doctors. ^{1 2 4 6 7}

How is MSLN-targeted CAR T-cell therapy different from other treatments for mesothelioma?

MSLN-targeted CAR T-cell therapy is unique because it uses genetically engineered T cells to specifically target and attack mesothelin, a protein highly expressed in mesothelioma tumors but not in healthy tissues. This approach is different from traditional treatments like chemotherapy and radiation, as it aims to enhance the body's immune response directly against the cancer cells. ^{1 2 3 4 8}

What is the purpose of this trial?

This study will test the safety of MSLN-targeted CAR-T cells at different doses to find the safest dose to give to people with MPM. The researchers want to see what effects, if any, the study treatment has on people with this type of cancer. This study is the first time that an MSLN-targeted CAR-T cell treatment with an anti-PD1 component is being given to people.

Research Team

Roisin O'Cearbhaill, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with mesothelioma who've had at least one treatment regimen, are not on high-dose steroids, and don't have other active cancers or certain heart/lung conditions. They must be in good physical condition (Karnofsky score ≥70%) and have a life expectancy of more than 4 months.

Inclusion Criteria

My mesothelioma affects both the lining of my abdomen and lungs, confirmed by tests.

I can finish palliative radiotherapy 2 days before starting lymphodepletion.

Your blood tests need to show a certain level of white blood cells and platelets, and your liver and kidney function need to be within a certain range.

Exclusion Criteria

I have had treatment for blood cancer or lymphoid malignancy in the last 5 years.

I am taking high doses of corticosteroids every day.

I am currently being treated for another cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Manufacturing

Patients undergo leukapheresis for the collection of PBMCs, followed by CAR T-cell manufacturing

4-6 weeks

Preconditioning

A preconditioning regimen of one dose of intravenous cyclophosphamide is administered 2-7 days before CAR T-cell infusion

1 week

Treatment

A single dose of M28z1XXPD1DNR CAR T cells is administered, followed by a minimum of 48 hours of hospital monitoring

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• MSLN-targeted CAR T-cell Therapy

Trial Overview The trial is testing different doses of MSLN-targeted CAR-T cells to find the safest dose for treating mesothelioma. It's the first time this therapy, which includes an anti-PD1 component, is being used in humans.

Participant Groups

Group I: Engineered Autologous T Cells Experimental Treatment 2 Interventions

Following eligibility screening and enrollment, patients will undergo leukapheresis for the collection of peripheral blood mononuclear cells (PBMCs), to enable generation of M28z1XXPD1DNR. Following successful M28z1XXPD1DNR CAR T-cell manufacturing, patients will be reevaluated for eligibility. A preconditioning regimen of one dose of intravenous (IV) cyclophosphamide 1.5 g/m2 will be administered 2-7 days before the infusion. A single dose of M28z1XXPD1DNR CAR T cells will be instilled into the pleural cavity via a pleural catheter or through an interventional radiology-guided needle. All patients will be monitored in the hospital for a minimum of 48 h following the administration of CAR T cells.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Atara Biotherapeutics

Industry Sponsor

Trials

14

Recruited

740+

Findings from Research

Anti-MSLN CAR-T-cell therapy has demonstrated a high safety profile in clinical trials, making it a promising option for treating solid tumors, although its efficacy remains limited.

Combining anti-MSLN CAR-T-cell therapy with standard treatments has shown significantly better outcomes than using the therapy alone, suggesting that combination strategies may enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges of Anti-Mesothelin CAR-T-Cell Therapy. Zhai, X., Mao, L., Wu, M., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Greece pubmed.ncbi.nlm.nih.gov

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor (CAR) T Cell Therapy for Malignant Pleural Mesothelioma (MPM). [2021]

4. England pubmed.ncbi.nlm.nih.gov

Mesothelin-targeted CAR-T cell therapy for solid tumors. [2021]

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

Therapeutic effiacy of T cells expressing chimeric antigen receptor derived from a mesothelin-specific scFv in orthotopic human pancreatic cancer animal models. [2022]

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

Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Challenges of Anti-Mesothelin CAR-T-Cell Therapy. [2023]

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

A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab. [2022]