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

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Median Overall Survival (OS) [Up to 18 months]. Median, years (90% Confidence Interval). Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 0.934 (0.934 to NA) [Median survival (MS) is calculated by using the Kaplan-Meier (KM) curve. The MS is found by seeing where the estimated KM curve intersects with the horizontal line indicating 50% survival (HL-50). The upper 90% confidence value for the MS is found by seeing where the upper confidence band (CB) for the KM estimate intersects with HL-50. For this analysis, the upper CB is 1 for the whole time period under study; which means that it never intersects with HL-50; and thus is not available to report].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Biomarker Analysis (Including CD3, CD4, CD8, PD1, PDL1, Monocytes, MDSC, IFN-gamma, IL-10, and TILs) Assessed Using Immunohistochemistry [Up to 18 months].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Incidence of Toxicity (CTCAE Version 4.0) [Up to 18 months]. Count Of Participants, Participants. Anorexia: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 1. Anxiety: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 1. Chills: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 2. Depression: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 1. Diarrhea: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 2. Dizziness: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 1. Dry Mouth: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 1. Fatigue: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 2. Fever: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 2. Gastroesophageal reflux disease: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 1. Headache: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 2. Myalgia: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 1. Nausea: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 2. Rash maculo-papular: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 2. Vomiting: Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS) [Up to 18 months]. Median, Years (90% Confidence Interval). Treatment (Anti-CD3 x Anti-EGFR BATs) (n=2): 0.934 (0.934 to NA) [Median survival (MS) is calculated by using the Kaplan-Meier (KM) curve. The MS is found by seeing where the estimated KM curve intersects with the horizontal line indicating 50% survival (HL-50). The upper 90% confidence value for the MS is found by seeing where the upper confidence band (CB) for the KM estimate intersects with HL-50. For this analysis, the upper CB is 1 for the whole time period under study; which means that it never intersects with HL-50; and thus is not available to report].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Quantitative Immune Response [Up to 18 months].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

TTP [Up to 18 months].