Results of a placebo-controlled phase III trial of immunotherapy with APC8015 for patients with hormone refractory prostate cancer (HRPC)

Abstract

4500 Background APC8015 is an immunotherapy cellular product consisting of autologous peripheral blood mononuclear cells enriched for a dendritic cell fraction pulsed with PA2024, a Prostatic Acid Phosphatase (PAP)-GM-CSF construct. We previously reported results including time to objective progression (TTP) and time to onset of disease related pain (TDRP) from a randomized trial in metastatic HRPC. Reported here are final overall survival (OS) data from this trial, as well as results of immunologic testing. Methods Patients (pts) with asymptomatic, metastatic HRPC were randomized (2:1) to receive APC8015 (n=82) or placebo (n=45) every 2 weeks x 3. Eligible pts had > 25% of cancer cells positive for PAP by central pathology review. The primary endpoint was TTP. TDRP was a secondary endpoint and pts were monitored for OS at 36 months. Monitoring was by weekly pain logs and serial radiologic imaging. Progression and pain were centrally reviewed and pts were followed per protocol for survival for 3 years following randomization. T-cell proliferation to PA2024 was evaluated by 3H-thymidine uptake. The T-Cell Stimulation Index (TCSI) was defined as: counts per minute (cpm) with antigen/cpm without antigen. The TCSI-ratio was defined as the median TCSI at 8 weeks/median TCSI at pre-treatment. Results 127 pts were randomized between 1/00 and 10/01. In an intent-to-treat (ITT) analysis, median OS was 25.9 months for pts on APC8015 compared with 22.0 months for those on placebo (p=0.020, log-rank, hazard ratio 1.625). At 36 months, 33% of APC8015 pts were alive, compared with 11% of placebo pts. The TCSI-ratio was 16.9 for APC8015 and 1.99 for placebo (p=.003, Wilcoxon Rank Sum). Treatment was generally well tolerated. Grade 1 and 2 fevers and rigors were the most common treatment-related AEs. Conclusions In an ITT analysis, treatment with APC8015 resulted in a statistically significant OS advantage of 3.9 months in pts with asymptomatic HRPC, representing the first survival advantage attributed to an immunotherapy product in prostate cancer. APC8015 pts also had an 8-fold increase in the TCSI-ratio. These data support this approach in the treatment of pts with metastatic HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dendreon Dendreon Dendreon Dendreon Dendreon Dendreon