RECRUITING

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

Conditions

Mesothelin Positive Mesothelin-Expressing Tumors Esophageal Adenocarcinoma Esophageal Adenocarcinomas Esophagogastric Adenocarcinoma Peritoneal Carcinomatosis Breast Neoplasms Diabetes Mellitus esophagastric adenocarcinoma CAR T-Cell Therapy 24-214

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase I Trial of Intraperitoneal Mesothelin-Targeted CAR T-Cell Therapy in Patients With Mesothelin-Positive Esophagogastric Adenocarcinoma With Peritoneal Carcinomatosis

Quick Facts

Study Start:2024-09-30

Study Completion:2028-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06623396

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 before the informed consent form signing date * Completion of systemic therapy at least 7 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 * 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 leukapheresis * 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 * 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) * 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 * 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	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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 before the informed consent form signing date
* Completion of systemic therapy at least 7 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
* 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 leukapheresis
* 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
* 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)
* 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
* 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

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Geoffrey Ku, MD

CONTACT

646-888-4588

kug@mskcc.org

Parastoo Dahi, MD

CONTACT

646-608-3733

dahip@mskcc.org

Principal Investigator

Geoffrey Ku, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Geoffrey Ku, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-30

Study Completion Date2028-09-30

Study Record Updates

Study Start Date2024-09-30

Study Completion Date2028-09-30

Terms related to this study

Keywords Provided by Researchers

mesothelin positive
mesothelin-expressing tumors
esophageal adenocarcinoma
esophageal adenocarcinomas
esophagastric adenocarcinoma
peritoneal carcinomatosis
CAR T-Cell Therapy
24-214

Additional Relevant MeSH Terms

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