Abstract C241: Phase I trial of EUS-guided intratumoral vaccination with recombinant Panvac-F and systemic Panvac-V in patients with locally advanced pancreatic cancer.

Abstract

Abstract Preclinical studies in our laboratory were the first to demonstrate the superiority of intratumoral poxvirus vaccines in overcoming immune escape and effectively treating murine solid tumor models. We present here the translation of these findings to a Phase I trial in six patients with locally advanced inoperable adenocarcinoma of the pancreas (NCT00669734). The first dose cohort of patients were treated using a combination of EUS (Endoscopic Ultrasound)-guided intrapancreatic tumor injection of recombinant Panvac-F (Fowlpox encoding MUC-1, CEA, TRICOM, 108 PFU) in addition to systemic Panvac-V (vaccinia, 2 × 108 PFU) and Panvac-F (109 PFU) boosts (accompanied by subcutaneous rH-GM-CSF, 100 mcg × 4 days). Patients received a total of 2 intrapancreatic injections of Panvac-F (2 weeks apart) with systemic Panvac-V and Panvac-F boosts given with GMCSF extending to day 71 (total of 2 intrapancreatic Panvac-F, 1 sc Panvac-V, 4 sc Panvac-F). Patients were allowed to transition to standard care at day 31. Patients were evaluated for toxicity, tumor progression, and serum CA 19–9 and CEA levels. Two of six patients were removed from study after approximately two weeks due to rapid disease progression and died one and six months after trial initiation. Of the remaining four, one had received prior treatment with gemcitabine followed by capecitabine and radiation and received no further treatment after vaccination; three received post-vaccination standard treatment with gemcitabine. Of the 4 patients with followup of greater than 6 mos, all have clinically stable disease (15 mos, 13 mos, 12 mos, 9 mos). One pt had a DLT (pancreatitis) that resolved allowing completion of protocol therapy. Results demonstrate that the “first in human” intrapancreatic administration of the full recombinant poxvirus regimen was well tolerated with encouraging stable disease duration. The trial is currently accruing patients at intrapancreatic dose level 2 (109 PFU). This study is supported by the NCI Cancer Therapy Evaluation Program (CTEP) and by NCI U01-CA07031 and P30-CA72720. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C241.