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

NCT ID: NCT06623396

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

Conditions: Official terms:
Adenocarcinoma
Breast Neoplasms
Esophageal Neoplasms
Carcinoma
Peritoneal Neoplasms

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

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: M28z1XXPD1DNR CAR
Description: 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.
Arm group label: Participants with Mesothelin-Positive Esophagogastric Adenocarcinoma with Peritoneal Carcinomatosis

Summary: 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.

Criteria for eligibility:
Criteria:
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 Inclusion Criteria for Leukapheresis: - 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 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 Inclusion Criteria for lymphodepleting chemotherapy/CAR T cell infusion - 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 o Immune checkpoint inhibitor therapy must be completed at least 28 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 Participant Exclusion Criteria Exclusion Criteria for Leukapheresis or Lymphodepleting chemotherapy/CAR T cell infusion: Participants are excluded from enrollment if any of the following criteria apply: - 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Address:
City: Basking Ridge
Zip: 07920
Country: United States

Status: Recruiting