T-Cell Therapy for Advanced Breast Cancer

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 (>0.4 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) <2.5x
ULN; for patients with liver metastases, ALT/AST <5x ULN is acceptable.

- 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