Phase I Study of Adoptive Immunotherapy for Advanced MUC1* Positive Breast Cancer with Autologous T Cells Engineered to Express a Chimeric Antigen Receptor, huMNC2-CAR44 Specific for a Cleaved Form of MUC1 (MUC1*)
1.Confirmation of diagnosis of breast cancer by internal pathology review of initial or subsequent biopsy or other pathologic material at FHCRC/SCCA. ER, PR, and HER2 status known and documented per ASCO/CAP guidelines.
2.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.
a.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.
b.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.
c.Patients with triple negative disease must have received at least 2 prior lines of chemotherapy in the metastatic setting.
3.MUC1* membrane expression =30% by immunohistochemistry on a tumor specimen obtained at screening or previous tumor specimen.
4.Patients must be 18 years of age or older, of any gender, race or ethnicity.
5.Patients must be capable of understanding and providing a written informed consent.
6.Patients must have a Karnofsky performance status of = 60%.
7.Patients must have measurable disease by at least one of the criteria below:
a.Extra skeletal disease that can be accurately measured by CT or MRI per RECIST 1.1,
b.Skeletal or bone-only metastases measurable by FDG PET imaging
8.Negative serum pregnancy test within 14 days before leukapheresis and within 28 days before 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.
9.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-CAR44 T cell infusion.
Other eligibility criteria may apply.
1.Patients requiring ongoing daily corticosteroid therapy at a dose of >15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable.
2.Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the PI.
3.Major organ dysfunction defined as:
a.Serum creatinine > 2 mg/dL
b.Bilirubin = 1.5 mg/dL with the following exception: Patients with known Gilbert disease, serum bilirubin > 3 mg/dL
c.AST or ALT = 2.5 x upper institutional limit of normal with the following exception: Patients with known hepatic metastases, AST or ALT > 3 x upper institutional limit of normal
d.Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing. Those with an FEV1 of
e.Significant cardiovascular abnormalities as defined by any one of the following:
i. NYHA class III or IV congestive heart failure, ii. clinically significant hypotension, iii. uncontrolled symptomatic coronary artery disease, or iv. a documented ejection fraction of
7.Treatment with investigational agent(s) within 30 days of planned lymphodepletion.
9.Uncontrolled active infection.
10.Anticipated survival of
12.Patients who have a contraindication to cyclophosphamide chemotherapy.
13.Known second malignancy that is progressing or requires active treatment.
14.Untreated CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate with documented stable disease as defined by no evidence of progression by imaging or symptoms for at least 4 weeks prior to enrollment.
15.Have psychiatric illness, social situation, or other medical condition that would preclude informed consent to limit compliance with study requirements, as determined by the investigator.
Other exclusion criteria may apply.