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Malignant Pleural DiseasePhase 1/2NCT02414269

Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin

A Phase 1/2 study testing iCasp9M28z T cell infusions, cyclophosphamide and pembrolizumab in people with Malignant Pleural Disease and Mesothelioma, run by Memorial Sloan Kettering Cancer Center at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this Phase I study is to test the safety of different doses of specially prepared immune cells (called "T cells") collected from blood. The Investigators want to find a safe dose of these modified T cells for patients who have malignant pleural disease. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
iCasp9M28z T cell infusions, cyclophosphamide and pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
113 participants
Where
6 sitesUnited States
Study dates
May 2015to 30 Apr 2027
Phase
Phase 1/2
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

  • Patients with MPD aged ≥18 years
  • Karnofsky performance status ≥70%
  • Patients with malignant pleural disease (MPD), pathologically confirmed at MSKCC (radiographic confirmation is acceptable for screening phase eligibility), and defined as one of the following (patients who have not yet received treatment may enroll in the screening portion only):
  • Malignant pleural mesothelioma - previously treated with at least one prior treatment regimen.
  • Non-small cell lung cancer metastatic to the pleura-previously treated with at least one prior treatment regimen (chemotherapy or targeted agent) and documented progression of disease. Patients with disease outside of the pleura will be discussed among study PI and Co-PIs prior to considered eligible for the study. Disease outside of the pleura must not require any immediate therapy per PI's discretion.
  • Breast cancer metastatic to the pleura- previously treated with at least one prior treatment regimen (chemotherapy or targeted agent) and documented progression of disease. Patients with disease outside of the pleura will be discussed among study PI and Co-PIs prior to be considered eligible for the study. Disease outside of the pleura must not require any immediate therapy per PI's discretion.
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  • Only patients with a diagnosis of malignant pleural mesothelioma will be included in cohort 9 and in the Phase II portion of the study
  • Expression of mesothelin must be confirmed by meeting one of the following criteria.
  • Mesothelin expression (>10% of the tumor expressing mesothelin) by immunohistochemical (IHC) analysis
  • Elevated serum SMRP levels (>1.0 nM/L).
  • Free flowing pleural effusion requiring management by placement of a pleural catheter. Patients with a functional pleural catheter already in place are eligible for the study, as long as there are no clinical concerns of infection.
  • OR
  • No free-flowing pleural effusion: an Interventional Radiologist has agreed that radiology-guided intrapleural or peritumoral injection of the CAR T cells is feasible.
  • Chemotherapy, targeted therapy (such as a tyrosine kinase inhibitor) or therapeutic radiotherapy must have been completed at least 14 days prior to administration of T cells. Continuation of hormonal therapy (ie for breast cancer) is acceptable. Prior immunotherapy with checkpoint blockade (i.e. PD1 inhibitor, PDL1 inhibitor or CTL4-antagonist or similar agent) must have been completed more than 1 month1prior to the T cell infusion.
  • Chemotherapy must have been completed at least 7 days prior to leukapheresis
  • Palliative radiotherapy must be completed at least 2 days prior to administration of cyclophosphamide
  • 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 I or lower according to CTCAE (version 4.0).
  • Lab requirements (hematology)
  • White blood cell (WBC) count ≥3000 cells/mm3
  • Absolute neutrophil count ≥1500 neutrophils/mm3
  • Platelet count ≥100,000 platelets/mm3 Lab requirements (serum chemistry)
  • Bilirubin ≤ 1.5x upper limit of normal (ULN)
  • Serum alanine aminotransferase and serum aspartate aminotransferase (ALT/AST) ≤.5x ULN
  • Serum creatinine ≤ 1.5x ULN or Cr > 1.5x ULN, but calculated clearances of >60
  • Negative screen for human immunodeficiency virus (HIV), hepatitis B virus (HBV) antigen, and hepatitis C virus (HCV). If testing was performed during the previous 3 months, there is no need to repeat testing, as long as documentation of results is provided to the study site. Subjects must receive counseling and sign a separate informed consent form for HIV testing.
  • Subjects and their partners with reproductive potential must agree to use an effective form of contraception during the period of drug administration and for 4 weeks after completion of the last administration of the study drug. An effective form of contraception is defined as oral contraceptives plus 1 form of barrier or double-barrier method contraception (condom with spermicide or condom with diaphragm).
  • Subjects must be able to understand the potential risks and benefits of the study and must be able to read and provide written, informed consent for the study

Who cannot join

  • Untreated or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that all of 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 CNS-directed therapy and the screening radiographic study;
  • Completion of radiotherapy ≥8 weeks prior to the screening radiographic study;
  • Discontinuation of corticosteroids and anticonvulsants ≥4 weeks prior to the screening radiographic study.
  • Non-small cell lung cancer metastatic to the pleura that extends outside of the pleura requiring immediate therapy
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  • Breast cancer metastatic to the pleura that extends outside of the pleura requiring immediate therapy
  • Prior history of seizure disorder
  • Patients currently receiving treatment for concurrent active malignancy Continuation of hormonal therapy (i.e. for breast cancer) is acceptable. Prior immunotherapy with checkpoint blockade (i.e. PD1 inhibitor, PDL1 inhibitor or CTL4-antagonist or similar agent) must have been completed more than 1 month prior to the T cell infusion.
  • Autoimmune or antibody-mediated disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis (Patients with a history of hypothyroidism will not be excluded)
  • History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry
  • Subjects with left ventricular ejection fraction (LVEF) less than 50%
  • Patients with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids
  • Baseline pulse oximetry is less than 92% on Room air
  • Pregnant or lactating women
  • An infection requiring antibiotic treatment within 7 days before the start of treatment (day 0)
  • A requirement for daily systemic corticosteroids for any reason or a requirement for other immunosuppressive or immunomodulatory agents. Topical, nasal, and inhaled steroids are permitted.
  • Administration of live, attenuated vaccine within 8 weeks before the start of treatment (day 0) and throughout the study
  • Any other medical condition that, in the opinion of the PI, may interfere with a subject's participation in or compliance with the study

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Memorial Sloan Kettering Basking Ridge (Consent and Follow-Up)

    Basking Ridge, New Jersey

  • Memorial Sloan Kettering Commack (Consent and Follow-Up)

    Commack, New York

  • Memorial Sloan Kettering Westchester (Consent and Follow-Up)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Consent and Follow-Up)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Consent and Follow-Up)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (Consent and Follow-Up)

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I/II Clinical Trial of Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin

The purpose of this Phase I study is to test the safety of different doses of specially prepared immune cells (called "T cells") collected from blood. The Investigators want to find a safe dose of these modified T cells for patients who have malignant pleural disease. They want to find out what effects these T cells have on the patient and the cancer (MPD).

Phase 2 part of the study, the investigators will test the dose in combination with another drug, pembrolizumab, to see what effects the study treatment has on malignant pleural mesothelioma.

Read the detailed description

This is an open-label, dose-escalating, non randomized, single-center, phase I/II study of mesothelin-targeted T cells administered intrapleurally as an infusion in patients with a diagnosis (histologically or cytologically documented) of MPD from mesothelioma, lung cancer, or breast cancer. Patients receiving pembrolizumab in cohort 9 only includes patients with a diagnosis of mesothelioma. The total number of patients studied will depend on the number of dose levels tested, up to a maximum dose of 6×10^7 mesothelin-targeted T cells/kg or until the maximum tolerated dose (MTD) is reached. In Phase I of this study, we anticipate infusing a minimum of 4 and a maximum of 54 evaluable patients. The total number of enrolled patients in Phase II of this study depends on the number of observed responses and ranges from 13-21 evaluable patients, including 6 patients treated at the final dose in Phase I.

For patients who were treated and were removed from study, duplicate enrollment is permitted if it is determined the patients could receive benefit. If the patients meet all eligibility criteria, they may receive treatment in a higher dose level cohort. Patients who are re-treated with CAR T cell therapy will not be considered new accruals. Outcomes of re-treated patients will be analyzed separately.

Patients may receive palliative radiotherapy for symptom management prior to or following the CAR T cell infusion. If a patient receives palliative radiotherapy, the study PI, treating Radiation Oncologist, and treating Medical Oncologist will decide whether to proceed with the infusion. Palliative radiotherapy must be completed at least 2 days prior to the administration of cyclophosphamide.

Patients in cohort 9 and in the Phase II portion of the study will begin treatment with pembrolizumab 4 weeks (+3/-1 week window) after completing CAR T cell administration. Patients will receive 3 doses of pembrolizumab given on a recurring schedule followed by reassessment. Patients responding or deriving clinical benefit, without unacceptable toxicity, will be followed for up to 6 months after the first dose of pembrolizumab and may continue pembrolizumab. Patients who cannot receive all 6 doses of pembrolizumab at MSK will be followed and medical records including images will be obtained from the treating physician.

Being tested
iCasp9M28z T cell infusions, cyclophosphamide, pembrolizumab
Keywords
modified T cells, cyclophosphamide, CAR T cells, 15-007, CAR, immunotherapy
Medical subject headings
Mesothelioma, Neoplasm Metastasis, Lung Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • iCasp9M28z T cell infusionsGenetic

    Administration through the pleural catheter- On day 0 patients will be treated with genetically modified T cells. Thirty to 60 minutes before T cell infusion, patients will be given 650 mg of acetaminophen orally and 25- 50 mg of diphenhydramine orally or intravenously, to prevent infusion-related reactions. The genetically modified T cells will be infused for at least 15 minutes and no more than 2 hours through the indwelling pleural catheter depending on the volume of the T cells. A physician will be available during the infusion. Please note, during formulation of iCasp9M28z T cells, under or over estimation of CAR modified T Cells may occur. Patient may receive an altered fractionation of the total dose or up to 35% over or under total cell dose with approval of the PI. Patients who do not have enough cells to match the current dose cohort will be treated in the cohort in which they have cells available

  • cyclophosphamideDrug

    Patients will receive cyclophosphamide intravenously (at 1.5 g/m^2)

  • pembrolizumabDrug

    Pembrolizumab will be given as 200 mg flat dose infusion intravenously.

Study groups in NCT02414269
Study groupRoleWhat they receive
modified T cells alone (without chemotherapy)ExperimentalFollowing enrollment, leukapheresis product will be obtained in the blood donor facility at MSKCC and cryopreserved in the Cell Therapy and Cell Engineering Facility (CTCEF). Before protocol treatment, the leukapheresis product will be thawed, and T cell isolation, transduction, and expansion of iCasp928z T cells will be performed in the MSKCC CTCEF Facility. It is estimated that it will take approximately 3 to 6 weeks to generate T cells for treatment.
Receives: Genetic: iCasp9M28z T cell infusions
modified T cells with cyclophosphamideExperimentalPatients will receive cyclophosphamide intravenously (at 1.5 g/m^2) , 2 - 7 (Day (-7) -(-2) days before T cell infusion. On Day 1 , patients will be admitted to the MSKCC Inpatient Service (if not already inpatients) for intravenous hydration, clinical monitoring, and blood work for immune monitoring. Standard MSKCC antiemetic therapy will be administered prior to chemotherapy to prevent nausea/vomiting. Administration of corticosteroids will be avoided as steroids may impede the efficacy of CAR T cells.
Receives: Genetic: iCasp9M28z T cell infusions; Drug: cyclophosphamide
CAR T cell and pembrolizumabExperimentalPembrolizumab 4 weeks (+3/-1 week window) after completing CAR T cell administration. Patients will receive 3 doses of pembrolizumab given on a recurring schedule followed by reassessment. Those responding or deriving clinical benefit, without unacceptable toxicity, will continue pembrolizumab. Patients will be followed weekly for the first four weeks. Patients in cohorts 9 and in Phase II will receive pembrolizumab 4 weeks(+3/- 1 week window) following CAR T cell administration.
Receives: Drug: pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite measure of severity and number of adverse events (AEs); changes in (clinical laboratory test findings (hematologic and chemistry); and physical examination. (Phase I)

    All AEs and laboratory toxicities will be graded using version 4 of the CTCAE.

    Measured: 1 year

  2. clinical benefit rate (phase II)

    rate will be defined as the proportion of patients with a response of complete response (CR), partial response (PR), and stable disease (SD) as measured by mRECIST criteria.

    Measured: at 12 weeks following the first dose of pembrolizumab

Secondary outcomes (1)

  1. Changes in serum levels of the biomarker soluble mesothelin related peptide (SMRP) (Phase I)

    Mesothelin is an immunogenic cell surface antigen, that is expressed at high levels in MPD and mesothelioma pleural fluid will be drained from the chest by thoracentesis or through a pleural catheter and will be preserved for analysis .

    Measured: 60 days (+/-5 days) after treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2015 (estimated)
  2. Study startMay 2015
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
113 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02414269
Sponsor's protocol ID
15-007
Status last verified
Jul 2026
First submitted
2 Apr 2015
Last updated
22 Jul 2026
Results posted
No

Publications

  • Barr T, Ma S, Li Z, Yu J. Recent advances and remaining challenges in lung cancer therapy. Chin Med J (Engl). 2024 Mar 5;137(5):533-546. doi: 10.1097/CM9.0000000000002991. Epub 2024 Feb 7.

    PubMed 38321811

  • Ghosn M, Cheema W, Zhu A, Livschitz J, Maybody M, Boas FE, Santos E, Kim D, Beattie JA, Offin M, Rusch VW, Zauderer MG, Adusumilli PS, Solomon SB. Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial. Lung Cancer. 2022 Mar;165:1-9. doi: 10.1016/j.lungcan.2022.01.003. Epub 2022 Jan 6.

    PubMed 35045358

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing iCasp9M28z T cell infusions, cyclophosphamide and pembrolizumab in people with Malignant Pleural Disease and Mesothelioma, run by Memorial Sloan Kettering Cancer Center at 6 sites 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 28 inclusion and 19 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 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Composite measure of severity and number of adverse events (AEs); changes in (clinical laboratory test findings (hematologic and chemistry); and physical examination. (Phase I) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02414269, which also lists 2 linked publications.

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 22 Jul 2026.

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