A multiple ascending dose, open-label, phase IIa study evaluating the safety and tolerability of PCK3145 administered intravenously in patients with metastatic hormone refractory prostate cancer (HRPC)

Abstract

4636 Background: PCK3145 is a synthetic 15-mer peptide derived from the prostate secretory protein (PSP94) sequence. PCK3145 has demonstrated antiproliferative and antitumoral activity in the PC3 xenograft mouse model and the Dunning rat R-3327 MLL model. No drug related toxicities were found in the animal studies. The objectives of PCK3145-UK-2001 clinical trial were to evaluate the safety and tolerability, the pharmacokinetics, and efficacy of PCK3145 in metastatic HRPC patients. Methods: Dose-escalation study in which successive cohorts of 4 patients received 4 ascending doses (5, 20, 40 and 80 mg/m2) of PCK3145. One cycle consist of IV administration of PCK3145, three time per week for 4 weeks followed by a 7-day post-treatment observation period. Pharmacokinetics of PCK3145 was determined for all patients at day 1 and day 26. Tumours were assessed by CT-Scan prior to and after the PCK3145 treatment. Results: Median age is 67 y (53–75) and the median time from HRPC to enrolment is 16.2 months (3–33). Sites of disease were mainly bone and lymph node. No drug related Adverse Event was observed for patients treated at 5, 20 and 40 mg/m2 but two patients treated at 80 mg/m2 experienced Serious Adverse Event (tachycardia and vasovagal reaction) possibly related to study medication. Preliminary results indicate that the half-life of PCK3145 is 20 minutes and tumor assessments suggest that the patients are having stable disease at least after one cycle. Five patients showed a decline in PSA levels (one of them by almost 50%). All patients that had plasma MMP-9 levels over 100 ug/L before treatment had reductions ranging from 34% to 90% after the first cycle while those with levels below 100 ug/L remained low. Conclusions: This clinical trial indicated that PCK3145 has an excellent safety profile for patients treated at 5, 20 and 40 mg/m2. Some toxicities, possibly related were observed at 80 mg/ m2. The marked reduction in plasma MMP-9 levels of patients receiving PCK3145 treatment indicates a biological effect, possibly related to control of metastasis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Procyon Biopharma, Inc. Procyon Biopharma, Inc. Procyon Biopharma, Inc. Procyon BioPharma, Inc.