Mesothelin-targeted CAR T-cell Therapy in Patients With Mesothelioma

NCT04577326 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 20-328
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Pleural Mesothelioma (MPM)

Keywords

Genetically Engineered Autologous T Cells; 20-328

Outcome Measures

Primary Outcomes (1)

• MTD of M28z1XXPD1DNR

  CTCAE v5.0 will be used to assess the severity of all treatment emerging toxicities/adverse events regardless

  2 years

Secondary Outcomes (1)

• overall response rate (ORR)

  2 years

Study Arms (1)

Engineered Autologous T Cells

EXPERIMENTAL

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.

Drug: cyclophosphamide; Biological: CAR T cells

Interventions

cyclophosphamide DRUG

A preconditioning regimen of one dose of intravenous (IV) cyclophosphamide 1.5 g/m\^2 will be administered 2-7 days before the infusion.

Engineered Autologous T Cells

CAR T cells BIOLOGICAL

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. Cohorts of 3 patients will be treated at each dose level, up to a maximum of 3 x 10\^7 T cells/kg or until the MTD has been reached.

Engineered Autologous T Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years
• Karnofsky performance status ≥70%
• Pathologically confirmed MPM
• Epithelioid or biphasic histologic diagnosis provided that ≥10% of the tumor expresses MSLN by IHC analysis
• Patients with peritoneal mesothelioma with pleural involvement are eligible only if there is radiographic and pathologic confirmation of mesothelioma in the pleural cavity and ≥10% of the tumor expresses MSLN by IHC analysis.
• Previously treated with at least 1 treatment regimen
• Measurable or evaluable disease (disease is considered evaluable but not measurable if it does not meet the eligibility criteria for mRECIST but is a manifestation of malignancy that can be followed qualitatively as an indicator of disease progression or treatment response)
• Chemotherapy, targeted therapy, or radiotherapy must be completed at least 7 days before leukapheresis.
• a. CPI must be completed at least 21 days before leukapheresis.
• Chemotherapy, targeted therapy, or therapeutic radiotherapy must be completed at least 14 days before administration of T cells.
• Palliative radiotherapy can be completed 2 days before lymphodepletion. Immunotherapy with CPI must be completed at least 42 days before administration of T cells.
• \. Any major thoracic (thoracotomy with lung or esophageal resection) or abdominal (laparotomy with organ resection) operation must have occurred at least 28 days before study enrollment. Patients who have undergone diagnostic VATS or laparoscopy can be included in the study.
• \. All acute toxic effects of any previous therapeutic or palliative radiotherapy, chemotherapy, or surgical procedures must have resolved to grade 1 (CTCAE v5.0).
• \. Lab requirements (hematology):
• a. Absolute neutrophil count ≥1.5 K/mcL b. Platelet count ≥100 K/mcL

You may not qualify if:

• Patients receiving therapy for concurrent active malignancy
• a. Patients receiving treatment for in situ skin malignancies are not excluded.
• Patients who received prior CAR T-cell therapy
• Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible if all the following criteria are met:
• Presence of measurable or evaluable disease outside of the CNS
• Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between completion of CNSdirected therapy and the screening radiographic study
• Completion of radiotherapy ≥8 weeks before the screening radiographic study
• Discontinuation of corticosteroids and anticonvulsants ≥4 weeks before the screening radiographic study
• History of seizure disorder
• Active autoimmune disease that has required systemic treatment in the past year (with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
• a. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Patients who are receiving daily systemic corticosteroids that are above physiological doses for any reason or who are under immunosuppressive or immunomodulatory treatment
• Patients with the below cardiac conditions:
• New York Heart Association stage III or IV congestive heart failure
• Myocardial infarction ≤6 months before enrollment

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Atara Biotherapeutics: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Cyclophosphamide; Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Roisin O'Cearbhaill, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase I dose-escalation trial.

Study Record Dates

• First Submitted: September 30, 2020
• First Posted: October 6, 2020
• Study Start: September 30, 2020
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)