Evaluation of biological activity of PCK3145 in metastatic hormone resistant prostatic cancer (HRPC) using serum markers

Abstract

4692 Background: Evaluation of efficacy for new treatment of HRPC is both challenging and rewarding as new targets are elucidated. Biological activity of PCK3145, a synthetic 15-mer peptide derived from the prostate secretory protein (PSP94) sequence was assessed by the analysis of several serum markers in the PCK3145-UK-2001 clinical trial. Tumor markers alone are not accepted by regulatory agency as a basis for marketing approval of oncology drugs, but may be used as elements in composite end points. With this first in man study, an attempt was made to find preliminary tumor markers correlation in this dose finding study with PCK3145 in HRPC patients. Methods: PCK3145 was administered i.v. in 4 cohorts of 4 patients with a dosage of 5, 20, 40 and 80 mg/m2. One cycle consist of an administration of PCK3145 three times a week for 4 weeks. Additional cycles may be proposed to patients in absence of toxicity and disease progression. Blood samples were collected prior and after each cycle. Serum markers includes hemoglobin, alkaline phosphatase, FSH, LH, tPSA, fPSA, PAP, Chromogranin A, Neuron-Specific Enolase, MMP-2, MMP-9, TIMP-1. Results: Patients received in average 2 cycles of PCK3145. One patient with a prostatectomy demonstrated an elevated level of FSH (over 60 IU/L) and had a 35 % reduction of the FSH level after the PCK3145 treatment. MMP-9 level was elevated (over 100 ug/L) in approximately 50 % of our patient population. Patients who had an elevated MMP-9 levels before treatment showed reductions by 72% (34% to 90%) after the very first cycle. Patients who had normal MMP-9 level (below 100 ug/L) remained normal after two cycles. PCK3145 seems to normalize the MMP-9 production. Evaluation of the MMP-9, PAP, Chromogranin A and PSA demonstrates clinical utility to monitor the disease status. Conclusions: The marked reduction in plasma MMP-9 levels of patients receiving PCK3145 treatment indicates a biological effect, and provides a potentially novel mechanism of action of this small molecule in these patients. These clinical results suggest the potential role of PCK3145 in the intervention of the metastatic process. 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.