T-Cell Therapy for Advanced Breast Cancer

A Phase I Clinical Trial to Evaluate the Safety and Tolerability of Mesothelin-Specific Chimeric Antigen Receptor-Positive T Cells in Patients With Metastatic Mesothelin-Expressing Breast Cancer

The purpose of this study is to test the safety of different doses of specially prepared T cells collected from the blood. The investigators want to find a safe dose of these modified T cells for patients who have metastatic HER2-negative breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Metastatic HER2-negative Breast
• Intervention / Treatment: Drug: Cyclophosphamide; Biological: Mesothelin-targeted T cells; Drug: AP1903

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States
      • Memorial Sloan Kettering Cancer Center (Consent and follow-up only)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Consent and Follow-Up only)
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen (Consent and follow-up only)
  • New York
    • Commack, New York, United States
      • Memorial Sloan Kettering Cancer Center at Commack (Consent and follow-up only)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (Consent and Follow-Up only)
    • West Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (Consent and follow-up only)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged ≥18 years with metastatic breast cancer
• Karnofsky performance status ≥70%

• Patients with breast cancer that is pathologically confirmed at MSKCC (pathology from outside institutions is acceptable for the screening phase of the protocol) and defined by the following:

  • HER2 negative (in cases of mixed HER2 results, the most recent pathology results considered reflective of the active cancer will be considered)
  • Previously treated with at least 1 chemotherapy regimen for metastatic disease and documented progression

• Expression of mesothelin must be confirmed by meeting 1 of the following criteria:

  • Mesothelin expression (>10% of the tumor expressing mesothelin) by IHC
  • Elevated serum SMRP levels (>1.0 nM/L)
• Presence of measurable or evaluable disease

• Chemotherapy, targeted therapy (such as a tyrosine kinase inhibitor), or radiotherapy must have been completed at least 14 days before administration of T-cells. Prior immunotherapy with checkpoint blockade (i.e., PD1 inhibitor, PDL1 inhibitor, or CTL4-antagonist or similar agent) must have been completed more than 1 month before the T-cell infusion.

  *Chemotherapy must have been completed at least 7 days prior to leukapheresis

• Any major operation must have occurred at least 28 days before study enrollment.
• All acute toxic effects of any previous radiotherapy, chemotherapy, or surgical procedures must have resolved to grade 1 or lower according to CTCAE

• Lab requirements (hematology):

  • White blood cell (WBC) count ≥3000 cells/mm^3
  • Absolute neutrophil count ≥1500 neutrophils/mm^3
  • Platelet count ≥100,000 platelets/mm^3

• Lab requirements (serum chemistry):

  • Bilirubin <1.5x upper limit of normal (ULN)
  • Serum alanine aminotransferase/serum aspartate aminotransferase (ALT/AST) <5x ULN
  • Serum creatinine <1.5x ULN or Cr >1.5x ULN, but calculated clearances of >60
• Negative screen for human immunodeficiency virus (HIV), hepatitis B virus (HBV) antigen, and hepatitis C virus (HCV). If testing was performed during the previous 3 months, there is no need to repeat testing, as long as documentation of results is provided to the study site. Subjects must receive counseling and sign a separate informed consent form for HIV testing.
• Subjects and their partners with reproductive potential must agree to use an effective form of contraception during the period of drug administration and for 4 weeks after completion of the last administration of the study drug. An effective form of contraception is defined as oral contraceptives plus 1 form of barrier or double-barrier method contraception (condom with spermicide or condom with diaphragm).
• Subjects must be able to understand the potential risks and benefits of the study and must be able to read and provide written, informed consent for the study.
• Availability of archival tumor tissues (FFPE tissue block or 10-15 unstained slides)

Exclusion Criteria:

• Untreated or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:

  • Presence of measurable or evaluable disease outside of the CNS;
  • 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 ≥8 weeks prior to the screening radiographic study;
  • Discontinuation of corticosteroids and anticonvulsants ≥4 weeks prior to the screening radiographic study.
• History of seizure disorder
• Patients currently receiving treatment for concurrent active malignancy. Prior immunotherapy with checkpoint blockade (i.e., PD1 inhibitor, PDL1 inhibitor, or CTL4-antagonist or similar agent) must have been completed more than 1 month prior to the T-cell infusion.
• Autoimmune or antibody-mediated disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis (patients with a history of hypothyroidism will not be excluded)
• Clinically significant cardiac disease (New York Heart Association class III/IV) or severe debilitating pulmonary disease
• Pregnant or lactating women
• Known active infection requiring antibiotics within 7 days of the start of treatment (Day 0)
• A requirement for daily systemic corticosteroids for any reason or a requirement for other immunosuppressive or immunomodulatory agents. Topical, nasal, and inhaled steroids are permitted.
• Administration of live, attenuated vaccine within 8 weeks before the start of treatment (Day 0) and throughout the study
• Any other medical condition that, in the opinion of the PI, may interfere with a subject's participation in or compliance with the study
• Participation in a therapeutic research study or receipt of an investigational drug within 30 days of T-cell infusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: T-cell infusion; A single blood volume leukapheresis for harvesting of PBMCs will be performed, As the transduced T cells will be frozen, the timing of leukapheresis is not defined & can vary from patient to patient. Subsequently, a single dose of mesothelin-targeted T cells will be infused via intravenous catheter or central line (i.e., mediport). Patients will be monitored in the hospital and discharged home after a minimum of 48 hours. Patients will be monitored closely as outpatients for the next 2 months. Patients will be followed weekly as outpatients for the first 8 weeks after treatment. All patients will be hydrated intravenously, premedicated with acetaminophen & diphenhydramine, & administered cyclophosphamide at 1.5 g/m2 2 to 7 days (Day -7 to Day -2) before administration of mesothelin-targeted T cells.

Drug: Cyclophosphamide; Biological: Mesothelin-targeted T cells; Drug: AP1903

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated does (MTD)	We have designed the dose-escalation using a standard 3+3 design. In this design, patients will be treated in sequential groups of 3 to 6 patients per T cell dose. With 4 dose levels, the projected trial size for this study is a minimum of 4 and a maximum of 24 patients.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Shanu Modi, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 2, 2016
• First Submitted That Met QC Criteria: June 6, 2016
• First Posted (Estimated): June 7, 2016

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; T-Cell; CAR; Triple-negative breast cancer; CAR T cells; Chimeric antigen receptor (CAR); Immunotherapy T-cell therapy; 16-040
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: 16-040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No