A Study of Mesothelin-Targeted CAR T-Cell Therapy in People With Esophagogastric Cancer

NCT ID: NCT06623396

Last Updated: 2025-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-30

Study Completion Date

2028-09-30

Brief Summary

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Participants will have a sample of their white blood cells, called T cells, collected using a procedure called leukapheresis. The collected T cells will be sent to a laboratory at Memorial Sloan Kettering to be changed (modified) to become MSLN-targeted CAR T cells, the CAR T-cell therapy that participants will receive during the study. Participant study therapy will take about 3-4 weeks.

Detailed Description

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Conditions

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Mesothelin Positive Mesothelin-Expressing Tumors Esophageal Adenocarcinoma Esophageal Adenocarcinomas Esophagogastric Adenocarcinoma Peritoneal Carcinomatosis Breast Neoplasms Diabetes Mellitus

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Participants with Mesothelin-Positive Esophagogastric Adenocarcinoma with Peritoneal Carcinomatosis

Participants will be diagnoses with Mesothelin-Positive Esophagogastric Adenocarcinoma with Peritoneal Carcinomatosis

Group Type EXPERIMENTAL

M28z1XXPD1DNR CAR

Intervention Type BIOLOGICAL

Participants with esophagastric adenocarcinoma will be treated with an intraperitoneal infusion of different doses of autologous T cells that have been genetically modified ex vivo to express the M28z1XXPD1DNR CAR. The CAR T cells will be manufactured in MSK's Center for Cell Engineering.

Interventions

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M28z1XXPD1DNR CAR

Participants with esophagastric adenocarcinoma will be treated with an intraperitoneal infusion of different doses of autologous T cells that have been genetically modified ex vivo to express the M28z1XXPD1DNR CAR. The CAR T cells will be manufactured in MSK's Center for Cell Engineering.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Aged ≥18 years
* Diagnosis of pathologically confirmed EG adenocarcinoma
* Diagnosis of metastatic or recurrent disease
* ECOG performance status of 0-1
* Life expectancy of ≥4 months


* Written informed consent for the study (from participant)
* Life expectancy of ≥4 months
* ECOG performance status of 0-1
* Histologic diagnosis that \& \>25% of the tumor expresses MSLN by IHC analysis. Archival tissue obtained up to 2 years before study enrollment is acceptable. IHC testing of a cell block from cytology (e.g., ascitic fluid) is acceptable if approved by the study pathologist. If adequate archival tissue is not available at screening, a fresh tumor biopsy should be obtained
* Stage IV disease with gross peritoneal carcinomatosis on imaging and/or microscopic peritoneal involvement by cytology or noted during diagnostic laparoscopy
* Disease progression or treatment intolerance after receiving at least 1 treatment regimen in the metastatic setting; patients with disease recurrence within 6 months of completing curative systemic therapy (chemotherapy, chemoradiation or adjuvant immunotherapy) are also eligible
* Patients with Her2 positive disease must have received ≥1 line of anti-Her2 based therapy
* At least 1 measurable or evaluable lesion per RECIST 1.1. Screening imaging must be obtained within 6 weeks of signing the informed consent form
* Completion of systemic therapy at least 7 days before leukapheresis

o Immune checkpoint inhibitor therapy must be completed at least 14 days before leukapheresis
* Lab requirements (hematology):

* Absolute neutrophil count ≥1.0 K/mcL
* Hemoglobin ≥9 gm/dL
* Platelet count ≥75 K/mcL
* Blood product transfusion or growth factor support cannot occur within 7 days of testing
* Lab requirements (serum chemistry):

* Bilirubin ≤1.5× upper limit of normal (ULN)
* Serum alanine aminotransferase and serum aspartate aminotransferase (ALT/AST) level ≤3× ULN
* Calculated clearance of ≥50 mL/min by Cockcroft-Gault equation
* Negative screen for infectious disease markers, including hepatitis B core antibody, hepatitis B surface antigen, hepatitis C antibody, HIV 1-2 antibody, HTLV antibody and syphilis antibody

o Note: Patients with a history of hepatitis B virus infection are eligible if the hepatitis B viral load is undetectable. Patients with a history of hepatitis C virus infection who were treated for hepatitis C and cured are eligible if the hepatitis C viral load is undetectable
* Serum pregnancy test with negative result at screening and preconditioning and must be willing to use effective and reliable contraception for at least 12 months after T cell infusion (for female participants of childbearing age)
* Resolution of all acute toxic effects of any previous therapeutic or palliative chemotherapy, radiotherapy, or surgical procedures to grade ≤1 (CTCAE v5.0), except for neuropathy and alopecia


* Life expectancy of ≥4 months
* ECOG performance status of 0-1
* At least 1 measurable or evaluable lesion per RECIST 1.1. Screening imaging must be obtained within 4 weeks before the date of lymphodepletion
* Completion of systemic therapy at least 14 days before lymphodepleting chemotherapy

o Immune checkpoint inhibitor therapy must be completed at least 28 days before lymphodepleting chemotherapy
* Lab requirements (hematology):

* Absolute neutrophil count ≥1.5 K/mcL
* Hemoglobin ≥8 gm/dL
* Platelet count ≥75 K/mcL
* Lab requirements (serum chemistry):

* Bilirubin ≤1.5× upper limit of normal (ULN)
* Serum alanine aminotransferase and serum aspartate aminotransferase (ALT/AST) level ≤3× ULN
* Calculated clearance of ≥50 mL/min by Cockcroft-Gault equation
* Serum pregnancy test with negative result within 7 days of planned lymphodepletion date and must be willing to use effective and reliable contraception for at least 12 months after T cell infusion (for female participants of childbearing age)
* Resolution of all acute toxic effects of any previous therapeutic or palliative chemotherapy, radiotherapy, or surgical procedures to grade ≤1 (CTCAE v5.0), except for neuropathy and alopecia

Exclusion Criteria

* Pregnant or lactating
* HIV, active hepatitis C virus, or active hepatitis B virus infection, as determined by quantitative PCR (patients who have undergone negative testing prior to leukapheresis do not require repeat testing)
* Receiving therapy for concurrent active malignancy

* Note: Patients receiving treatment for in situ skin malignancies are not excluded.
* Patients with any malignancy diagnosed \>3 years before that is thought to be curatively treated and/or has a low risk of recurrence are eligible. Patients may continue to receive adjuvant therapy at the time of study enrollment (e.g., adjuvant hormonal therapy for curatively treated breast cancer).
* Known hematologic malignancy requiring treatment in the preceding 5 years or a known history of lymphoid malignancy
* Previous receipt of CAR T cell therapy or any other cellular therapy
* Previous mesothelin-directed therapy Any major abdominal surgery (laparotomy with resection of gastrointestinal tract or organ resection) that is completed \<28 days before study enrollment. Patients who have undergone diagnostic laparoscopy can be included in the study without regard to timing
* 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 of the following criteria are met:

* 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 ≥4 weeks before the screening radiographic study
* Active autoimmune disease that has required systemic treatment within 1 year before leukapheresis (with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)

o Note: 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.
* Receiving daily systemic corticosteroids ≥10 mg of prednisone daily or equivalent or receiving immunosuppressive or immunomodulatory treatment
* Any of the following 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
* Left ventricular ejection fraction ≤40%
* 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 time point
* Known active infection requiring antibiotic treatment 7 days before leukapheresis

o Note: Treatment can be delayed at the discretion of the treating physician to allow the patient to recover from the infection.
* Any other medical condition, e.g. fever \>38.0 degrees C, that, in the opinion of the PI, may interfere with the subject's participation in or compliance with the study
* Receipt of live, attenuated vaccine within 8 weeks before the planned lymphodepleting chemotherapy date
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geoffrey Ku, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Geoffrey Ku, MD

Role: CONTACT

646-888-4588

Parastoo Dahi, MD

Role: CONTACT

646-608-3733

Facility Contacts

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Geoffrey Ku, MD

Role: primary

646-888-4588

Geoffrey Ku, MD

Role: primary

646-888-4588

Geoffrey Ku, MD

Role: primary

646-888-4588

Geoffrey Ku, MD

Role: primary

646-888-4588

Geoffrey Ku, MD

Role: primary

646-888-4588

Geoffrey Ku, MD

Role: primary

646-888-4588

Geoffrey Ku, MD

Role: primary

646-888-4588

Related Links

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http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

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24-214

Identifier Type: -

Identifier Source: org_study_id

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