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Her2-BATs for the Treatment of Breast Cancer Leptomeningeal Metastases

Trial Status: Active

This phase I trial studies the best dose and side effects of Her2-BATs in treating patients with breast cancer that has spread to the meninges (the thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal metastases). Her2-BATs is an anti-cancer agent created from patients own immune cells (T-cells) coated ('armed") with and experimental drug made up of bispecific antibodies called Herceptin and OKT3. The Her2-BATs antibody is able to react against human breast cancer. An antibody is a type of protein that helps protect the body from bacteria and disease. Her2-BATs works by seeking out certain cancer cells like on breast tumor cells that have a molecule called Her2 on their surface. The Her2-BATs antibody may target the Her2 receptor on the cancer cell and use the body's own immune system to destroy those cancer cells.

Inclusion Criteria

  • Be willing and able to provide written informed consent for the trial
  • 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
  • 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
  • Karnofsky performance status (KPS) of >= 60
  • Eligible for intraventricular (IVENT) catheter/reservoir placement as determined by neurosurgery
  • Absolute lymphocyte count >= 500/mm^3 (performed within 10 days of confirmation of eligibility)
  • Absolute neutrophil count (ANC) >= 1,000 /mcL (performed within 10 days of confirmation of eligibility)
  • Platelets >= 100,000 / mcL (performed within 10 days of confirmation of eligibility)
  • Hemoglobin >= 8 g/dL (performed within 10 days of confirmation of eligibility)
  • Blood urea nitrogen (BUN) =< 1.5 X upper limit of normal (ULN) (performed within 10 days of confirmation of eligibility)
  • Serum creatinine within the normal limits OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min/1.73 m^2 (performed within 10 days of confirmation of eligibility)
  • Serum total bilirubin =< 2 X ULN (performed within 10 days of confirmation of eligibility)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X ULN (performed within 10 days of confirmation of eligibility)
  • Albumin >= 2.5 mg/dL (performed within 10 days of confirmation of eligibility)
  • Note: Patients with brain metastases in addition to LM are eligible for this protocol

Exclusion Criteria

  • Current severe increased intracranial pressure with clinical or imaging findings suggestive of herniation, status epilepticus, or other serious complications requiring emergency or urgent intervention
  • Patients who cannot have magnetic resonance imaging (MRI) studies for any reason (intolerance, medical contraindication, etc.)
  • 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
  • Patients with unresolved autoimmune toxicity
  • Patients with a known disorder that increases the risk of bleeding (e.g., Hemophilia, von Willebrands disease, or clinically significant clotting factor deficiency)
  • 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
  • Administration of any investigational agents, immunomodulating agents, radiation therapy or chemotherapy for metastatic breast cancer (MBC) within the 7 days before the 80 mL blood draw to collect cells for study treatment
  • Has human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or known active hepatitis B (e.g. hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Pregnancy or lactation at the time of registration
  • Psychiatric or addictive disorders or other conditions that in the opinion of the investigator would preclude the patient from complying with the study protocol


University of Virginia Cancer Center
Status: ACTIVE
Contact: Camilo Enrique Fadul
Phone: 434-982-4415


I. To determine the safety and feasibility of intraventricular (IVENT) infusions of HER2Bi-armed activated T cells (Her2 BATs) therapy in a phase I dose escalation trial in participants with leptomeningeal metastases (LM) from breast cancer.

II. To determine the maximum tolerated dose (MTD) for Her2 BATs in participants with LM from breast cancer.


I. To determine if the IVENT injection of Her2 BATs will cause a shift in the immune biomarkers in the blood and cerebrospinal fluid (CSF).

II. To correlate immune response in the CSF with imaging and clinical response.

III. To estimate objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

IV. To estimate changes in symptom burden from the brain/spine tumor before and following Her2 BATs treatment, as measured by the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP).

OUTLINE: This is a dose-escalation of HER2Bi-armed activated T cells.

Patients receive methotrexate via intraventricular infusion twice weekly for 3-4 weeks. Beginning 7 days after chemotherapy infusion, patients receive test dose of HER2Bi-armed activated T cells via intraventricular infusion over 30 minutes. Patients then receive HER2Bi-armed activated T cells via intraventricular infusion over 30 minutes weekly for 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 week, 30 days, and every 3 months for 2 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Virginia Cancer Center

Principal Investigator
Camilo Enrique Fadul

  • Primary ID 20805
  • Secondary IDs NCI-2019-06212, BATS Breast LM
  • ID NCT03661424