Phase I study of intravesical recombinant fowlpox-GM-CSF (rF-GMCSF) and/or recombinant Fowlpox-TRICOM (rF-TRICOM) in patients with advanced bladder cancer

Abstract

4755 Background: We have shown that TCC biopsies express high levels of IL10 mRNA and in preclinical models that this IL10 suppresses antigen presenting cell (APC) activity and antitumor immunity. To enhance APC activity and antitumor immunity, we are accruing a Phase I study of intravesical recombinant fowlpox encoding GMCSF, or LFA-3, ICAM-1, B7.1 (TRICOM) genes in pts with advanced bladder cancer. Methods: In this three arm study (A. rF-GMCSF, B. rF-TRICOM, C. Combination), pts with bladder cancer scheduled for cystectomy receive 4 weekly doses of intravesical virus (3 pts per dose level, initial dose 5.7 - 7 X 107 PFU). Study endpoints are toxicity, MTD, bioavailability (degree of gene transfer in cystectomy specimen); immunity to vector and reporter genes; and local cellular and cytokine responses in the bladder wall. Results: Six pts with high grade invasive bladder cancer have been treated in this ongoing study. Overall, treatment was well tolerated. 3/3 Arm B pts experienced transient elevations in liver transaminases with 1/3 reaching DLT. 2/3 each Arm A, B pts had similar stage and grade disease in cystectomy specimen as in pretreatment biopsy. 1/3 Arm A pts had no tumor identified in the bladder or nodes following treatment. 1/3 Arm B pts had no residual tumor in the bladder but 2/8 positive nodes. H&E staining of the cystectomy specimen showed variable immune cell infiltration of bladder wall and enlarged lymph nodes in both arms. Conclusions: Pts receiving intravesical rF-GMCSF and rF-TRICOM at the initial dose level tolerated therapy. Pathology showed variable immune infiltration of bladder wall, tumor, and enlarged draining lymph nodes. Bioavailability, immunohistochemistry and immune studies are ongoing. No significant financial relationships to disclose.