The purpose of this study is to understand the safety and estimate the efficacy of anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) armed fresh peripheral blood mononuclear cells (HER2 FPBMC) for patients with metastatic breast or prostate cancer. Participants receive 5 weekly doses of CD33 FPBMC by intravenous infusion followed by 4 infusions every other week.
Once subjects are determined to be eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure. The T cells in the mononuclear cells are coated with bispecific antibody to activate the T cells and the mononuclear cells are re-infused into the patients so the T cells can multiply and kill cancer cells. At least 72 hours after the leukapheresis procedure, study treatment will start. After 5 HER2 FPBMC infusions, participants will have another leukapheresis procedure. Before, throughout and following study treatment, research blood will be collected to better understand immune response. Disease status will be checked regularly during and after study treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Participants will receive 5 weekly infusions of HER2 FPBMC infusions followed by 4 additional infusions every other week.
University of Virginia
Charlottesville, Virginia, United States
RECRUITINGDose limiting toxicities (DLTs)
DLTs in the dose escalation phase
Time frame: During the first 5 infusions (5 weeks) for each participant
Total cells collected
Total cells collected for each participant (for creation of cell product) at each timepoint for collection
Time frame: For each participant, prior to starting study treatment (induction) and then prior to boost/retreatment infusions (about 9-10 weeks later)
Overall response rate
Percent of participants that have a response (complete or partial) to study treatment
Time frame: During and immediately after study treatment for each participant (a maximum of ~20 weeks)
Progression free survival
Time from start of study treatment through first disease progression afterward (for each participant)
Time frame: For up to 3 years after last infusion for each participant (about 3 1/2 years)
Overall survival
Time from start of study treatment through death from any cause (for each participant)
Time frame: For up to 3 years after last infusion for each participant (about 3 1/2 years)
Adverse events
As described using CTCAE v5.0
Time frame: During and through ~30 days after end of study treatment (maximum of about 24 weeks)
Development of specific cytotoxicity by PBMCs (of participants) as measured by cytotoxicity or IFN-γ EliSpots responses
To breast and prostate cancer cell lines, respectively
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Time frame: Multiple timepoints during and through ~30 days after end of study treatment (maximum of about 24 weeks)
Serum antibodies to breast or prostate cancer cell lines and ELISA for IgG-specific antibody to HER2 and EGFR2
Time frame: Multiple timepoints during and through ~30 days after end of study treatment (maximum of about 24 weeks)
Survival kinetics of HER2 FPBMCs after a single infusion
Time frame: Multiple timepoints before and after the first 5 infusions (week 5)