Abstract P5-16-06: A phase 2 randomized trial of docetaxel (DOC) alone or in combination with therapeutic cancer vaccine, CEA-, MUC-1-TRICOM (PANVAC)
Authors: Heery CR , Ibrahim NK , Mohebtash M , Madan RA , Arlen PM , Bilusic M , Kim JW , Singh NK , Hodge S , McMahon S , Steinberg SM , Hodge JW , Schlom J , Gulley J 
Published: August 2014

Abstract
Background: A previous phase 1/2 trial of PANVAC, a poxviral based cancer vaccine, suggested clinical efficacy in some patients (pts) with breast and ovarian cancer and evidence of immunologic activity. Preclinical data showed DOC can modify tumor phenotype, making tumor cells more amenable to T-cell mediated killing. The goal was to determine if DOC and PANVAC could synergize and improve clinical outcomes compared with DOC alone.
Methods: This is an open-label randomized phase 2 multi-center trial designed to enroll 48 pts with metastatic breast cancer to receive DOC in combination with PANVAC (A) or alone (B). Cross-over was allowed so that pts randomized to B could receive the vaccine upon progression. Eligibility included ECOG performance status &lt;1 and normal organ and immune function with no limits on previous lines of therapy, but pts may not have received DOC for metastatic disease. Her2+ pts on trastuzumab were allowed to continue trastuzumab on trial. All pts received DOC 35mg/m2 weekly × 3 doses during 28-day cycles. Pts on A were “primed” with recombinant vaccinia-PANVAC study day 1. Three weeks later, they began 28-day cycles of DOC with “boost” recombinant fowlpox-PANVAC given on day 1, given until progression. CT and bone scans were performed after 3 cycles and then every 2 cycles. 1° endpoint was PFS., with a phase 2.5 statistical design, with the intent of identifying a trend toward benefit to guide a larger trial design. A p value of 0.10 is considered a strong trend. 2° endpoints included overall survival and immunologic correlative studies. Immunologic assays included analysis of T cell and NK cell activation, presence and activity of regulatory T cells, and ELISPOT assays. Immune correlative analysis was done using multiparametric flow cytometry analysis of immune cell subpopulations from peripheral blood mononuclear cells (PBMCs) of pts and comparing those findings using Boolean logic with the immune assays and clinical outcomes.
Results: Enrollment of 48 pts completed in February 2012 (A, n=25; B, n=23). Five pts remain on treatment (2 on A, 3 on B). Pt and tumor characteristics were well matched. Analysis through August 2, 2012 (median follow-up of 5.1 months for pts on study), indicates PFS is 6.6 vs. 3.8 months in A vs. B (p = 0.12, HR=0.67, 95% CI: 0.34 to 1.31). Analysis of the adverse events on both arms demonstrated very little difference between the two groups. The only statistically significant differences were increases in the frequency of grade 1 and 2 edema (p = 0.018) and injection site reactions (p &lt;0.0001) in the combination arm. Immune analysis and correlation to pt clinical outcomes are ongoing and will be available for presentation at the time of the meeting. There are not yet enough events to perform a comparison of overall survival in the two groups.
Conclusion: This randomized study suggests the combination of PANVAC with DOC in metastatic breast cancer may provide a clinical benefit compared to DOC alone. The clear separation of the curves indicates potential benefit, which is not statistically significant, likely due to the small number of pts enrolled. This study was hypothesis generating and may provide both rationale and statistical assumptions for a larger definitive randomized study.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-16-06.