Login to Access Video or Poster Abstract: MP70-15
Sources of Funding: Sophiris Bio Corp.

Introduction

Intra-prostatic injection of PRX302 may provide a targeted approach to focally lysing tumor cells, avoiding the side-effects of radical treatment. It is a genetically modified pore-forming protein (aerolysin) activated by enzymatically active PSA. Our proof-of-concept IRB-approved study aimed to determine toxicity, side-effects and early efficacy as well as to determine optimum treatment delivery of MRI-ultrasound fusion-guided intra-prostatic injection of PRX302.

Methods

18 men with histologically proven, clinically significant, localized low-intermediate risk prostate cancer associated with an MRI lesion were recruited (PSA /=4mm (May/2015-Nov/2015). Patients had a single lesion injected transperineally using MRI-ultrasound image-fusion software (SmartTarget®), under general anaesthetic with up to 5mL of a standard dosing solution (20ug/mL) of PRX302. Follow-up occurred at 2 days and at 2, 6, 12, 24 and 26 weeks. A mpMRI-targeted transperineal biopsy of the treated area was performed at 24 weeks. All men who enrolled completed the study.

Results

Median age and PSA were 66.50 years (IQR 13.00) and 6.25ng/ml (IQR 2.45). 4 patients (22%) had high volume Gleason 6 and 14 (78%) had Gleason 7 cancer with median lesion size 0.3mL (IQR 0.2-0.5). The administration of PRX302 was well tolerated with no serious adverse events and no new safety signals. At 24 weeks following treatment, 2 had complete tumour ablation (no histological evidence of cancer). These 2 showed reductions in PSA of 3.0 to 2.2ng/mL (26.7%) and 5.7 to 4.8ng/mL (15.8%), respectively. Seven had partial response defined as reductions in MCCL or Gleason grade. 9 had no histological response, with some experiencing increases in MCCL or grade.

Conclusions

Our proof-of-concept study shows that a single intraprostatic administration of PRX302 has a biological effect on prostate tumor cells when focally injected with low side-effect profile. Optimizing the dosing and delivery of PRX302 based on tumour size may increase response rates and will be tested in a multicenter phase 2 study.

Funding

Sophiris Bio Corp.