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

Launched by MEMORIAL SLOAN KETTERING CANCER CENTER · Sep 30, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new type of treatment called mesothelin-targeted CAR T-cell therapy for people with certain types of esophagogastric cancer, which includes esophageal adenocarcinoma and other related cancers. The treatment involves collecting a participant's white blood cells, specifically T cells, and sending them to a lab where they will be modified to better fight the cancer. After this process, participants will receive the modified T cells back, and the whole process takes about 3-4 weeks.

To participate in this trial, individuals must be at least 18 years old and have a confirmed diagnosis of metastatic or recurrent esophageal adenocarcinoma. They should also have a good performance status, meaning they can carry out daily activities with minimal issues. Participants will need to meet certain health criteria, such as having a life expectancy of at least 4 months and no active infections. If eligible, participants can expect close monitoring throughout the study, and the trial team will provide support and information about what to expect during the treatment. Overall, this trial aims to explore a promising new approach to treating a challenging form of cancer.

Gender

ALL

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 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
• • 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 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
• • 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