Malignant Pleural Mesothelioma (MPM)Phase 1NCT04577326
Mesothelin-targeted CAR T-cell Therapy in Patients With Mesothelioma
A Phase 1 study testing cyclophosphamide and CAR T cells in people with Malignant Pleural Mesothelioma (MPM), run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma (MPM)
- What is being tested?
- cyclophosphamide and CAR T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2020to 30 Sep 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- 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.
- 9. 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.
- 10. All acute toxic effects of any previous therapeutic or palliative radiotherapy, chemotherapy, or surgical procedures must have resolved to grade 1 (CTCAE v5.0).
- 11. Lab requirements (hematology):
- Absolute neutrophil count ≥1.5 K/mcL b. Platelet count ≥100 K/mcL
- 12. Lab requirements (serum chemistry):
- Bilirubin ≤1.5x upper limit of normal (ULN) b. Serum alanine aminotransferase and serum aspartate aminotransferase (ALT/AST) level ≤5x ULN c. Serum creatinine level ≤1.5x ULN or creatinine >1.5x ULN but calculated clearances of >60 by Cockcroft-Gault Equation
- 13. Negative screen for infectious disease markers including Hepatitis B core antibody, Hepatitis B surface antigen, Hepatitis C antibody, HIV 1-2 antibody, HTLV 1-2 and Syphilis (rapid plasma regain profile) Note - Patients with history of prior hepatitis B virus (HBV) infection are eligible if the HBV viral load is undetectable. Patients with a history of hepatitis C virus (HCV) infection who were treated for hepatitis C and cured are eligible if hepatitis C viral load is undetectable.
- 14. Life expectancy at the time of screening ≥4 months
Who cannot join
- Patients receiving therapy for concurrent active malignancy
- 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
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- 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)
- 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
- History of myocarditis
- Serious uncontrolled cardiac arrhythmia, unstable angina, or uncontrolled infection
- Patients with left ventricular ejection fraction ≤40%
- Patients with active interstitial lung disease/pneumonitis or a history of interstitial lung disease/pneumonitis requiring treatment with systemic steroids
- Baseline pulse oximetry <90% on room air at the screening timepoint
- Pregnant or lactating women
- Subjects and their partners with reproductive potential must agree to use an effective form of contraception during treatment and for 1 year following treatment.
- Known active infection requiring antibiotic treatment 7 days before the start of treatment (Day 0). Note: treatment can be delayed at the discretion of the treating physician to allow the patient to recover from the infection.
- Administration of live, attenuated vaccine within 8 weeks before the start of treatment (Day 0) and for 100 days following treatment.
- Any other medical condition that, in the opinion of the PI, may interfere with a subject's participation in or compliance with the study
- Any patient deemed to be noncompliant by the study team for administration of a high risk treatment agent and for close follow-up after treatment as required by the protocol
- Patients with known hematologic malignancy requiring treatment in the preceding 5 years or a known history of lymphoid malignancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065
About this study
Official title: A Single-Arm, Open-Label, Phase I Trial to Assess the Safety of Genetically Engineered Autologous T Cells Targeting the Cell Surface Antigen Mesothelin With Cell-Intrinsic Checkpoint Inhibition in Patients With Mesothelioma
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)
- Being tested
- cyclophosphamide, CAR T cells
- Keywords
- Genetically Engineered Autologous T Cells, 20-328
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
A preconditioning regimen of one dose of intravenous (IV) cyclophosphamide 1.5 g/m^2 will be administered 2-7 days before the infusion.
CAR T cellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: cyclophosphamide; Biological: CAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of M28z1XXPD1DNR
CTCAE v5.0 will be used to assess the severity of all treatment emerging toxicities/adverse events regardless
Measured: 2 years
Secondary outcomes (1)
overall response rate (ORR)
modified RECIST (mRECIST; v1.0)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2020
- Study start30 Sep 2020
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Pleural Mesothelioma (MPM)Studies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase I dose-escalation trial.
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Atara Biotherapeutics
- Responsible party
- Sponsor
- Investigators
- Roisin O'Cearbhaill, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04577326
- Sponsor's protocol ID
- 20-328
- Status last verified
- Oct 2026
- First submitted
- 30 Sep 2020
- Last updated
- 29 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm, Open-Label, Phase I Trial to Assess the Safety of Genetically Engineered Autologous T Cells Targeting the Cell Surface Antigen Mesothelin With Cell-Intrinsic Checkpoint Inhibition in Patients With Mesothelioma
- ClinicalTrials.gov ID
- NCT04577326
- Acronym / sponsor ID
- 20-328
- Conditions
- Malignant Pleural Mesothelioma (MPM)
- Keywords
- Genetically Engineered Autologous T Cells, 20-328
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Atara Biotherapeutics
- Study start
- 30 Sep 2020 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 6 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase I dose-escalation trial.
| Arm | Type | Receives |
|---|---|---|
| Engineered Autologous T Cells | Experimental | Drug: cyclophosphamide, Biological: CAR T cellsFollowing 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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Aged ≥18 years
- Karnofsky performance status ≥70%
- Pathologically confirmed MPM
- 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)
Key exclusion criteria (27 listed)
- Patients receiving therapy for concurrent active malignancy
- 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:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamideA preconditioning regimen of one dose of intravenous (IV) cyclophosphamide 1.5 g/m^2 will be administered 2-7 days before the infusion. | Drug | Engineered Autologous T Cells |
| CAR T cellsA 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. | Biological | Engineered Autologous T Cells |
Primary outcome
MTD of M28z1XXPD1DNR
Time frame: 2 years
CTCAE v5.0 will be used to assess the severity of all treatment emerging toxicities/adverse events regardless
1 secondary outcome
overall response rate (ORR)
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roisin O'Cearbhaill, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cyclophosphamide and CAR T cells in people with Malignant Pleural Mesothelioma (MPM), run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD of M28z1XXPD1DNR (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.