| Eligibility |
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
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