NCT06623396RecruitingPhase 1
A Phase I Trial of Intraperitoneal Mesothelin-Targeted CAR T-Cell Therapy in Patients With Mesothelin-Positive Esophagogastric Adenocarcinoma With Peritoneal Carcinomatosis
Memorial Sloan Kettering Cancer Center7 sites in 1 country18 target enrollmentStarted: September 30, 2024Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 18
- Locations
- 7
- Primary Endpoint
- Number of treatment-emergent adverse events
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •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.
- •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
Arms & Interventions
Participants with Mesothelin-Positive Esophagogastric Adenocarcinoma with Peritoneal Carcinomatosis
Experimental
Participants will be diagnoses with Mesothelin-Positive Esophagogastric Adenocarcinoma with Peritoneal Carcinomatosis
Intervention: M28z1XXPD1DNR CAR (Biological)
Outcomes
Primary Outcomes
Number of treatment-emergent adverse events
Time Frame: 1 year
The primary objective of this study is to assess the safety of M28z1XXPD1DNR CAR T cells administered through the peritoneal cavity. CTCAE v5.0 will be used to assess the severity of all treatment-emergent toxicities and adverse events, regardless of reporting requirements
Maximum Tolerated Dose of M28z1XXPD1DNR CAR T cells
Time Frame: Up to 1 year
Determine the maximum tolerated dose of M28z1XXPD1DNR CAR T cells administered through the peritoneal cavity.
Secondary Outcomes
No secondary outcomes reported
Investigators
Study Sites (7)
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