Extended survival in second-line pancreatic cancer after therapeutic vaccination

2576 Background: Therapeutic vaccines represent a novel approach for the treatment of pancreatic cancer. The generation of cytotoxic T cells requires at least 2 signals: antigen presentation to the T cell receptor and T cell costimulation. PANVAC-VF contains the genes for CEA, MUC-1, and 3 costimulatory molecules (B7.1, LFA-3, and ICAM-1) in 2 viral vectors to optimize presentation of antigen to T cells. Previous studies utilizing this approach have demonstrated a correlation between the generation of tumor-specific cytotoxic T cells and overall survival (OS) following administration of pox virus-based therapeutic anti-tumor vaccines. Here, we update the previously reported results of two Phase I studies of related vaccines in patients with advanced pancreatic cancer. Methods: Safety was the primary objective of both studies. Twenty-two patients with pancreatic cancer (Stage III or IV) were enrolled (20 with metastatic disease; all had received prior therapy). Based on preclinical and clinical studies, an optimized regimen of a priming dose on day 0 followed by boosting doses on days 14, 28, and 42 was utilized. GM-CSF (100 μg) was given on the day of each injection and for 3 consecutive days. Patients who were clinically stable were able to continue vaccinations monthly. All patients continue to be followed for survival. Results: The most common adverse event (AE) related to the vaccines was grade 1 injection site reaction (erythema, swelling, pruritis, blister, induration, and pain). Other common AEs were fatigue, anorexia, nausea, vomiting, fever, headache, and myalgia. No serious adverse events related to vaccine occurred. Median OS in the two studies was 7.9 and 6.3 months. One year survival was 33% and 30%. 18 month survival in the first study is 25% and has not been reached in the second trial. Conclusions: Historical control data suggest that the expected median OS in patients with metastatic pancreatic cancer in the second-line setting is approximately 3 months. Although these studies were small and uncontrolled, these data suggest that treatment with PANVAC-VF is well tolerated and results in prolonged OS in this patient population. A randomized, controlled Phase III trial is underway to test this hypothesis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Therion Biologics Therion Biologics