Once subjects are determined eligible, blood will be collected in order to make the HER2
BATs. For HER2 BATs, the white blood cells, specifically T cells, are then mixed with two
proteins - OKT3 and IL-2 -- which activates the cells to multiply. After approximately 14
days in culture, the activated T cells are coated with OKT3 and trastuzumab/Herceptin
(HER2Bi), and washed to remove excess Herceptin in order to produce bispecific antibody armed
T cells (BATs). Cells are then frozen and stored until scheduled to be infused. Up to 2 weeks
following blood collection, participants will undergo surgery to place the catheter/reservoir
into the lateral ventricle of the brain to allow intraventricular administration of HER2 BATs
and a chemotherapy agent methotrexate. A few weeks later, participants will receive the
intraventricular methotrexate in order to control disease while the BATs product is being
manufactured. About 4-5 weeks following the initial blood collection and at least 7 days
after receiving methotrexate, study treatment will begin with a test dose of HER2 BATs. If
this dose is well tolerated by the participant, she will then receive 8 weekly doses of HER2
BATs at the assigned dose level.
1. Be willing and able to provide written informed consent for the trial.
2. Participants must be female.
3. Histologically confirmed breast cancer (any Her2, estrogen receptor (ER), or
progesterone receptor (PR) expression) with leptomeningeal metastasis (LM) as
determined by imaging and/or cerebrospinal fluid (CSF) cytology.
4. 18 years of age or older.
5. Women of reproductive potential must agree to use an effective method of contraception
during therapy. Effective methods include intrauterine device (IUD), vasectomy of the
male partner, diaphragm with spermicide, cervical cap with spermicide, contraceptive
sponge, male or female condom, or hormonal contraceptive.
6. Karnofsky Performance Status (KPS) of ≥60.
7. Eligible for intraventricular (IVENT) catheter/reservoir placement as determined by
8. Demonstrate adequate organ function as defined below. All screening labs should be
performed within 10 days of confirmation of eligibility.
Absolute lymphocyte count ≥ 500/mm3 Absolute neutrophil count ≥ 1000/mcL Platelets ≥
100,000 / mnL Hemoglobin ≥ 8 g/dL BUN ≤ 1.5 x upper limit of normal (ULN) Serum creatinine
within the normal limits OR measured or calculated creatinine clearance ≥ 60 mL/min 1.73m2
Serum total bilirubin ≤ 2 x ULN OR AST (SGOT) and ALT (SGPT) ≤ 5 x ULN Albumin ≥ 2.5 mg/dL
1. Current severe increased intracranial pressure with clinical or imaging findings
suggestive of herniation, status epilepticus, or other serious complications requiring
emergency or urgent intervention.
2. Patients who cannot have MRI studies for any reason (intolerance, medical
3. Patients with a history of another malignancy within 1 year of study enrollment with
the following exceptions: patients with history of ductal carcinoma in situ (DCIS),
squamous cell skin cancers, or other in situ carcinomas are not excluded.
4. Patients with unresolved autoimmune toxicity.
5. Patients with a known disorder that increases the risk of bleeding (e.g., Hemophilia,
von Willebrands disease, or clinically significant clotting factor deficiency).
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
7. Administration of any investigational agents, immunomodulating agents, radiation
therapy or chemotherapy for MBC within the 7 days before the 80 mL blood draw to
collect cells for study treatment.
8. Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known active Hepatitis
B (e.g. HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
9. Pregnancy or lactation at the time of registration.
10. Psychiatric or addictive disorders or other conditions that in the opinion of the
investigator would preclude the patient from complying with the study protocol.