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

Status: administratively complete

This phase Ib/II trial studies the side effects and best dose of bispecific antibody armed activated T-cells when given together with aldesleukin and sargramostim and to see how well they work in treating patients with pancreatic cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Bispecific antibody armed activated T-cells are the patient's own T cells that are coated with a bispecific antibody comprising 2 antibodies chemically joined together. These antibodies have specific targets and binding properties that may give the T cells a greater ability to seek out, attach to, and kill more cancer cells.

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
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; 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
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

PRIMARY OBJECTIVES:

I. Confirm in a single dose phase I (3 to 6 patients [pts]) that 8 infusions of 10^9 epidermal growth factor receptor (EGFR) bispecific antibody armed activated T cells (BATs) (anti-CD3 OKT3/anti-EGFR bispecific antibody armed activated T lymphocytes) 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 10^9 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.

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 OKT3/anti-EGFR bispecific antibody armed activated T lymphocytes 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 OKT3/anti-EGFR bispecific antibody armed activated T lymphocytes 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 T-cell infusion and continuing twice weekly until the final infusion.

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

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

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