Bispecific Antibody Armed Activated T-cells With Aldesleukin and Sargramostim in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

PRIMARY OBJECTIVES:

I. Confirm in a single dose phase I (3 to 6 patients [pts]) that 8 infusions of 10^10
epidermal growth factor receptor (EGFR) bispecific antibody armed activated T cells (BATs)
given twice per week in combination with interleukin (IL)-2 (aldesleukin) (300,000
IU/m^2/day) and granulocyte-macrophage colony stimulating factor (GM-CSF) (sargramostim) (250
ug/m^2/twice weekly) beginning 3 days before the 1st infusion and ending on the day of the
last infusion is safe.

II. Perform a phase II clinical trial to estimate the clinical efficacy of 8 infusions of
10^10 EGFR BATs in combination with IL-2 and GM-CSF in 39 evaluable pts (including the 3-6
pts in the single dose phase I).

SECONDARY OBJECTIVES:

I. Determine if infusions of EGFR BATs significantly increase cellular or humoral
anti-pancreatic cancer (PC) responses by peripheral blood mononuclear cells (PBMC) at
different time points after last EGFR BATs infusion and if those responses persist beyond 2
months (mos).

II. Obtain original tumor paraffin blocks prior to treatment and evaluate blocks for cluster
of differentiation (CD)3, CD4, CD8, programmed cell death (PD)1/programmed cell death ligand
(PDL)1, monocytes subpopulations, myeloid-derived suppressor cells (MDSC), and cytoplasmic
interferon (IFN)-gamma and IL-10 by immunohistochemical staining to quantitate type and
number of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment to estimate
whether the type and number correlate with clinical responses.

III. To determine the time to progression (TTP).

OUTLINE: This is a phase Ib, dose-escalation study of anti-CD3 x anti-EGFR-bispecific
antibody armed activated T-cells followed by a phase II study.

Patients receive one of the following standard chemotherapy regimens at the discretion of the
treating physician: gemcitabine hydrochloride intravenously (IV) over 30 minutes; gemcitabine
hydrochloride IV over 30 minutes and paclitaxel albumin-stabilized nanoparticle formulation
IV over 30-40 minutes; oxaliplatin IV over 2 hours, fluorouracil IV over 46 hours and
leucovorin calcium IV over 2 hours; or fluorouracil IV over 46 hours, leucovorin calcium IV
over 2 hours, irinotecan hydrochloride IV, and oxaliplatin IV over 2 hours. Approximately 2
weeks after standard chemotherapy completion, patients receive anti-CD3 x
anti-EGFR-bispecific antibody armed activated T-cells IV over 5-30 minutes twice weekly for 4
weeks. Patients also receive aldesleukin subcutaneously (SC) and sargramostim SC on day -3
before the first anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells infusion
and continuing twice weekly until the final infusion.

After completion of study treatment, patients are followed up for 18 months.

Inclusion Criteria:

- Histological or cytological proof of pancreatic adenocarcinoma; must have locally
advanced or metastatic pancreatic cancer who have received at least first line
chemotherapy and may have responding, stable or progressive disease

- Expected survival >= 3 months

- Karnofsky performance scale (KPS) >= 70% or Southwestern Oncology Group (SWOG)
performance status 0 or 1

- Absolute neutrophil count (ANC) >= 1,000/mm^3

- Lymphocyte count >= 400/mm^3

- Platelet count >= 75,000/mm^3

- Hemoglobin >= 8 g/dL

- Serum creatinine < 2.0 mg/dl, creatinine clearance >= 50 ml/mm (can be calculated or
measured)

- Total bilirubin =< 2 mg/dl (biliary stent is allowed)

- Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic
transaminase (SGOT) < 5.0 times normal

- Left ventricular ejection fraction (LVEF) >= 45% at rest (multigated acquisition scan
[MUGA] or echocardiogram [Echo])

- Females of childbearing potential, and males, must be willing to use an effective
method of contraception

- Females of childbearing potential must have a negative pregnancy test within 7 days of
being registered for protocol therapy

Exclusion Criteria:

- Any chemotherapy related toxicities from prior treatment (> grade 2 per Common
Terminology Criteria for Adverse Events [CTCAE] version [v]4.0)

- Known hypersensitivity to cetuximab or other EGFR antibody

- Treatment with any investigational agent within 14 days prior to being registered for
protocol therapy

- Symptomatic brain metastasis

- Chronic treatment with systemic steroids or another immuno-suppressive agent

- Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy
or significant traumatic injury within 28 days prior to being registered for protocol
therapy

- Active liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis

- Known human immunodeficiency virus (HIV) infection

- Active bleeding or a pathological condition that is associated with a high risk of
bleeding (therapeutic anticoagulation is allowed)

- Has an active infection requiring systemic therapy

- A serious uncontrolled medical disorder that in the opinion of the investigator may be
jeopardized by the treatment with protocol therapy

- Females must not be breastfeeding

- Patient (Pt) may be excluded if, in the opinion of the principal investigator (PI) and
investigator team, the pt is not capable of being compliant