RecruitingPhase 1NCT06623396
A Study of Mesothelin-Targeted CAR T-Cell Therapy in People With Esophagogastric Cancer
A Phase I Trial of Intraperitoneal Mesothelin-Targeted CAR T-Cell Therapy in Patients With Mesothelin-Positive Esophagogastric Adenocarcinoma With Peritoneal Carcinomatosis
Sponsor
Memorial Sloan Kettering Cancer Center
Enrollment
18 participants
Start Date
Sep 30, 2024
Study Type
INTERVENTIONAL
Conditions
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.
Eligibility
Min Age: 18 Years
Inclusion Criteria43
- 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 Criteria27
- 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
Interventions
BIOLOGICALM28z1XXPD1DNR 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.
Locations(7)
View Full Details on ClinicalTrials.gov
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NCT06623396
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