Once subjects are determined eligible, white blood cells (lymphocytes) are collected via
leukapheresis procedure approximately 3 to 4 weeks prior to the first BATs infusion. The
white blood cells, specifically T cells, are then mixed with two proteins in order to
activate 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 leukapheresis, 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 leukapheresis 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.
Inclusion Criteria:
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
neurosurgery.
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
Exclusion Criteria:
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
contraindication, etc.).
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
study requirements.
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.
