This protocol will confirm toxicities and estimate the clinical efficacy of combining anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed activated T cells (EGFR BATs) given to patients with locally advanced or metastatic pancreatic cancer who have received at least one dose of first line chemotherapy and may have responding, stable or progressive disease. Phase Ib will confirm a safe dose of 8 infusions, given twice weekly, of EGFR-BATs in 3 to 6 subjects. The phase II portion of the trial will test the clinical efficacy of this dose in 22 patients (including those in Phase Ib).
Once subjects are determined eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure at approximately 3 to 4 weeks prior to first EGFR-BATs infusion. 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 the OKT3 and cetuximab to produce bispecific antibody armed T cells (BATs). Cells are then frozen and stored until scheduled to be infused. Within one to two weeks prior to infusion of the study treatment, subjects will receive one dose of chemotherapy. The choice of chemotherapy agent(s) is at the discretion of the treating physician. At approximately 4 weeks following leukapheresis procedure, twice weekly or weekly infusions of the BATs cells will take place (twice weekly for participants enrolled before DATE and weekly for participants enrolled after DATE). A total of eight twice weekly infusions or four weekly infusions will be given over a four week period. Please note that the weekly dose for both groups of participants is the same; participants that received twice weekly dosing received half of the weekly dose at each infusion. Follow-up appointment schedule will include clinic visits at 1 to 2 weeks, 4 to 5 weeks, 2 months, 4 months and 6 months following the last infusion of BATs cells.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Subjects will receive one dose of standard of care chemotherapy prior to twice weekly or weekly infusions of EGFR BATs for 4 weeks.
University of Virginia
Charlottesville, Virginia, United States
Incidence of adverse events
Safety will be assessed by incidence and severity of adverse events, changes in laboratory findings, physical examinations, vital signs, and the number of dose limiting toxicities and other discontinuations due to adverse events.
Time frame: From the beginning of treatment (bridging chemotherapy) until no sooner than 30 days following the last study treatment
Overall survival
An improvement in median overall survival (OS), defined as an increase from historical data of 8.7 months to 18.0 months.
Time frame: Until subject's death or study closure (whichever occurs first) for an average of 36 months from study treatment completion
Cellular or humoral anti-pancreatic cancer responses
These will be measured in peripheral blood mononuclear cells
Time frame: Every 2-6 months after the last EGFR BATs infusion for as long as the response lasts -- an average of 4 months
Clinical Efficacy
Progression-free survival, measured by immune-related response criteria (irRC)
Time frame: Imaging will be performed prior to treatment, 2 months after the last BATs infusion, then according to standard of care for an average of 12 months
Examine tumor tissue for immune system cells, cytokines and proteins to estimate whether the type and number of immune cells correlates with clinical responses
These immune system cells, cytokines and proteins include CD3, CD4, CD8, PD1/PDL1, monocytes subpopulations, MDSCs, and cytoplasmic IFN-y, tumor infiltrating lymphocytes, and IL-10. This will be measured using immunohistochemical staining to quantitate type and number of immune system cells, cytokines, and proteins to estimate whether the type and number correlate with clinical responses.
Time frame: Tumor paraffin blocks from tissue collected prior to treatment will be batched and analyzed within 1 year of completion of study accrual
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