t-cell therapy for advanced breast cancer

Conditions: Breast Cancer; Metastatic HER2-negative Breast

Summary: 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.


Eligibility criteria:
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, 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

Keywords: t-cell chimeric antigen receptor (car) car t cells triple-negative breast cancer immunotherapy t-cell therapy 16-040 immunotherapy car