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

NCT06623396 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 24-214
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of treatment-emergent adverse events

  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

  1 year

• Maximum Tolerated Dose of M28z1XXPD1DNR CAR T cells

  Determine the maximum tolerated dose of M28z1XXPD1DNR CAR T cells administered through the peritoneal cavity.

  Up to 1 year

Study Arms (1)

Participants with Mesothelin-Positive Esophagogastric Adenocarcinoma with Peritoneal Carcinomatosis

EXPERIMENTAL

Participants will be diagnoses with Mesothelin-Positive Esophagogastric Adenocarcinoma with Peritoneal Carcinomatosis

Biological: M28z1XXPD1DNR CAR

Interventions

M28z1XXPD1DNR CAR BIOLOGICAL

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.

Participants with Mesothelin-Positive Esophagogastric Adenocarcinoma with Peritoneal Carcinomatosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Peritoneal Neoplasms; Breast Neoplasms; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Geoffrey Ku, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Geoffrey Ku, MD

CONTACT

646-888-4588; kug@mskcc.org

Parastoo Dahi, MD

CONTACT

646-608-3733; dahip@mskcc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 2, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (7)