NCT02620865

BATS With in Combination With Low Dose IL-1 and GM-CSF for Advanced Pancreatic Cancer

Phase Ib/II Treatment of Advanced Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Bispecific Antibody Armed Activated T-Cells (BATs) in Combination With Low Dose IL-2 and GM-CSF

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Barbara Ann Karmanos Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Metastatic Pancreatic Adenocarcinoma
• Recurrent Pancreatic Carcinoma
• Stage III Pancreatic Cancer
• Stage IV Pancreatic Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Aldesleukin	Given SC
BIOLOGICAL	Antibody Therapy	Given anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV
DRUG	Fluorouracil	Given IV
DRUG	Gemcitabine Hydrochloride	Given IV
DRUG	Irinotecan Hydrochloride	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Leucovorin Calcium	Given IV
DRUG	Oxaliplatin	Given IV
DRUG	Paclitaxel Albumin-Stabilized Nanoparticle Formulation	Given IV
BIOLOGICAL	Sargramostim	Given SC

Timeline

• Start date: 2015-12-01
• Primary completion: 2021-06-21
• Completion: 2021-06-21
• First posted: 2015-12-03
• Last updated: 2023-05-15
• Results posted: 2023-05-15

Locations

1 site across 1 country: United States