Autologous huMNC2-CAR44 or huMNC2-CAR22 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*)

Inclusion Criteria18

• Please note that results of tests and/or procedures conducted as per standard of care purposes may be used for research purposes if conducted within the protocol-defined window prior to screening/leukapheresis and/or T-Cell Therapy.
• Confirmation of diagnosis of breast cancer by pathology review of initial or subsequent biopsy or other pathologic material at the City of Hope Pathology department. ER, PR, and HER2 status known and documented per ASCO/CAP guidelines.
• For dose expansion cohorts, tumors with ER and/or PR ≥1% will be considered hormone receptor positive. Tumors with ER and PR \<1% will be considered hormone receptor negative. HER2 status will be determined by IHC or FISH per ASCO/CAP guidelines. Patients will be allocated to expansion cohorts according to guidelines in table below.
• Dose expansion cohorts
• Expansion Cohort Hormone Receptor status HER2 status Luminal ER and/or PR \>/=1% positive Negative by IHC or FISH HER2 positive Any ER or PR status Positive by IHC or FISH Triple Negative ER and PR \<1% Negative by IHC or FISH
• Patients must have received standard metastatic systemic therapy per NCCN guidelines or institutional practice which are known to confer benefit. No maximum on number of prior systemic treatment regimens.
• Patients with hormone receptor positive disease must have received at least 3 prior endocrine therapies and at least 2 prior lines of chemotherapy in the metastatic setting.
• Patients with HER2 positive breast cancer must have received at least 3 prior HER2- directed therapies (trastuzumab, pertuzumab, TDM-1 or others) in the metastatic setting.
• Patients with triple negative disease must have received at least 2 prior lines of chemotherapy in the metastatic setting.
• MUC1\* membrane expression ≥30% by immunohistochemistry on a tumor specimen obtained at screening or previous tumor specimen that is less than 6-months old (see Appendix I for examples of MUC1\* expression patterns).
• Patients must be 18 years of age or older, of any gender, race or ethnicity.
• Patients must be capable of understanding and providing a written informed consent.
• Patients must have a Karnofsky performance status of ≥60%.
• Patients must have measurable disease by at least one of the criteria below:
• Extra skeletal disease that can be accurately measured by CT or MRI per RECIST 1.1,
• Skeletal or bone-only metastases measurable by FDG PET imaging.
• Negative serum pregnancy test within 14 days of planned leukapheresis and within 28 days of lymphodepleting chemotherapy for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year.
• Fertile male and female patients must be willing to use an effective contraceptive method before, during, and for at least 4 months after the huMNC2-CAR T cell infusion.