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.
Inclusion Criteria:
1. Histological or cytological proof of pancreatic adenocarcinoma. Must have locally
advanced or metastatic pancreatic cancer and received at least one dose of
chemotherapy (any treatment line) and may have responding, stable or progressive
disease
2. Expected survival ≥ 3 months
3. ECOG Performance Status 0 or 1
4. Left Ventricular Ejection Fraction (LVEF) ≥ 45% at rest (MUGA or Echo)
5. Age ≥ 18 years at the time of consent (Written informed consent and HIPAA
authorization for release of personal health information)
6. Females of childbearing potential, and males, must be willing to use an effective
method of contraception
7. Females of childbearing potential must have a negative pregnancy test within 10 days
prior to "on study" status. If a urine or serum test is positive or cannot be
confirmed as negative, the other (urine or serum pregnancy test, whichever was not
performed first) will be required.
8. Demonstrate adequate hepatic, renal, and bone marrow function as defined below; all
hematological, renal, and hepatic screening labs should be performed within 10 days
prior to "on study" status (alpha gal testing must be within the regular screening
period).
- Absolute lymphocyte count ≥ 400/mm3
- Absolute neutrophil count (ANC) ≥ 1,000/mm3
- Platelets ≥ 75,000/mm3
- Hemoglobin ≥ 8 g/dL
- Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be
used in place of creatinine or CrCl) < 2.0 mg/dl OR ≥50 ml/mm
- Serum total bilirubin ≤ 2 mg/dl (biliary stent is allowed)
- AST (SGOT) and ALT (SGPT) < 5.0 times normal
- Alpha 1,3 Galactose IgE ("alpha gal") < 0.35 IU/ml or "negative"
Exclusion Criteria:
1. Known hypersensitivity to cetuximab or other EGFR antibody
2. Treatment with any investigational agent within 14 days prior to first study
intervention (apheresis) for protocol therapy
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to first study
intervention (apheresis). Replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.
4. Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy
or significant traumatic injury within 28 days prior to "on-study" status
5. Active liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis
6. Is HIV positive or has evidence of active Hepatitis C virus or active Hepatitis B
virus. If initial Hepatitis C test shows a positive result, the patient should have a
Hepatitis viral load test to confirm. If initial HIV or Hepatitis B virus testing
shows a positive result, no further testing will be done.
7. Active bleeding or a pathological condition that is associated with a high risk of
bleeding (therapeutic anticoagulation is allowed)
8. Has an active infection requiring systemic therapy
9. A serious uncontrolled medical disorder that in the opinion of the Investigator may be
jeopardized by the treatment with protocol therapy
10. Has a known history of active TB (Bacillus Tuberculosis)
11. Has had prior chemotherapy, radiation, hormonal, monoclonal antibody (mAb) or targeted
small molecule therapy, within 2 weeks prior to the first study procedure (apheresis).
Subjects who have not recovered to <Grade 3 from an adverse event due to a previously
administered agent are not eligible.
12. Has received a live vaccine within 30 days of first study procedure (apheresis).
13. History of a recent myocardial infarction (within one year), a past myocardial
infarction (more than one year ago) along with current coronary symptoms requiring
medications.
14. Has history of another malignancy within the past 5 years. Exceptions include
- basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has
undergone potentially curative therapy
- in situ cervical cancer.
15. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
17. Females must not be breastfeeding
18. Pt may be excluded if, in the opinion of the PI and investigator team, the pt is not
capable of being compliant
