Abstract B100: Panvac-F and Panvac-V: Phase I study of intratumoral and systemic vaccination
Authors: Poplin Elizabeth A. , August David A. , Moss Rebecca A. , Ben-Menachem Tamir , Michael Hazar , Repaka Aparna , Artymyshyn Renee , Chan Chang , Gulley James L. , DiPaola Robert S. , Lattime Edmund C. 
Published: October 2015

Abstract
Patients with adenocarcinoma of the pancreas were treated using a combination of EUS-guided intrapancreatic tumor injection and systemic boost using PANVAC-F and PANVAC-V in this first-in-man Phase I trial. The study represents the translation of our unique demonstration in murine models of bladder and orthotopic mammary tumors that anergy to systemic immunization using antigen encoding vaccinia recombinants could be overcome by immunization into the tumor microenvironment. Consented patients with locally advanced or minimally metastatic pancreatic cancer received EUS-guided intrapancreatic injections (IT) of recombinant Panvac-F (Fowlpox encoding MUC-1, CEA, TRICOM), systemic subcutaneous (SC) Panvac-V (vaccinia) and SC Panvac-F boosts. Systemic SC vaccines were accompanied by subcutaneous rH-GM-CSF, 100 mcg X 4 days. Patients received 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 IT 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 and tumor progression. Follow-up care was provided by referring oncologists. In this dose escalation study, the first cohort of 6 pts received IT Panvac-F (10 8 PFU), SC Panvac-V (2 X 10 8 PFU), and SC Panvac-F (10 9 PFU). The second dose cohort of 8 pts received IT Panvac-F (10 9 PFU), SC Panvac-V (2 X 10 8 PFU), and SC Panvac-F (10 9 PFU ). At dose level 1, 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. At dose level 2, one patient was removed due to rapidly progressive disease and died at 1 mo and a second patient withdrew following 1 IT inoculation and died at month 16. Of the remaining 10 pts, 3 presented with distant metastatic disease (Median Survival 7 mos, range 1-25) and 7 presented without distant metastases (Median Survival 16 mos, range 3-35). Of note, none of the 7 patients presenting without metastatic disease developed distant visceral metastases, by imaging available to us but died of sequellae associated with progressive local disease. Of the above 10 pts, all but one transitioned initially to treatment with gemcitabine-based therapy. (the remaining pt did not begin systemic treatment). Initial RNAseq transcriptome analysis of Fine Needle Aspirate (FNA) comparing Day 1 and Day 14 samples demonstrated a significant increase in a series of chemokines associated with the induction of an immune response in the tumor microenvironment. A planned series of immunologic and genetic analyses are underway. Results demonstrate that the “first in man” intrapancreatic administration of recombinant poxvirus was well tolerated with the complete regimen suggesting an encouraging period of stable disease. The finding that none of the patients who presented without distant visceral metastases developed such would be consistent with the generation of a systemic immune response with effects on seeded metastatic cells. Analysis of local and systemic immune responses is currently proceeding and may provide further insights. This study is supported by the NCI Cancer Therapeutics Evaluation Program (CTEP) and by NCI U01-CA07031 and P30-CA72720.
Citation Format: Elizabeth A. Poplin, David A. August, Rebecca A. Moss, Tamir Ben-Menachem, Hazar Michael, Aparna Repaka, Renee Artymyshyn, Chang Chan, James L. Gulley, Robert S. DiPaola, Edmund C. Lattime. Panvac-F and Panvac-V: Phase I study of intratumoral and systemic vaccination. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B100.