Introduction

Patients who have recurrences of superficial urothelial carcinoma after BCG have limited therapeutic options. We are conducting a randomized phase II clinical trial in which patients who have recurrence after prior BCG undergo either repeat induction BCG or BCG combined with a cancer vaccine (PANVAC). In this study, we report our analysis of the initial immunologic response for the patients enrolled thus far.

Methods

The immunologic responses of all patients enrolled thus far were assessed. Three tumor-specific antigens (Brachyury, CEA, and MUC1) were assessed using an overlapping 15-mer peptide pool spanning the entire length of each of the peptides. HLA was used as a negative control and CEFII was used as a positive control. The tumor associated antigen (TAA) response was evaluated at an early time point (1 month after therapy initiation/1 week after 2nd vaccine administration) and at a later time point (3-4 months after therapy initiation/1 week after 4th vaccine administration). A positive response was defined as antigen levels above 250 (absolute number of cells producing cytokine) after subtracting for background.

Results

There were a total of 16 patients enrolled thus far: Eight patients were randomized to the BCG-only arm and eight patients were randomized to the BCG+PANVC arm. The median number of BCG instillations prior to enrollment in both groups was 6 (range 5-19). 25% of patients also had intravesical chemotherapy prior to enrollment (2 patient had Mitomycin C, 2 patients had Valrubicin). There was a higher rate of all responses in the BCG+PANVAC (mean TAA value 734) arm than in the BCG alone arm (mean TAA value 434) (p<0.01), and a higher rate of responses attributable to the brachyury antigen (p=0.03). There was also a higher rate of response when CEA and MUC1 were evaluated together. The CD8 response appeared to be greater than the CD4 response for patient in the PANVAC arm but not in the BCG only arm. _x000D_

Conclusions

BCG + PANVAC appears to induce an immunological response that is greater than BCG alone in many patients. The impact of this immunological response on patient outcomes will continue to be assessed as the trial matures. _x000D_

Funding

NIH intramural funding