Novel LHRH-receptor-targeted cytolytic peptide, EP-100: first-in-human phase I study in patients with advanced LHRH-receptor-expressing solid tumorsReport as inadecuate




Novel LHRH-receptor-targeted cytolytic peptide, EP-100: first-in-human phase I study in patients with advanced LHRH-receptor-expressing solid tumors - Download this document for free, or read online. Document in PDF available to download.

Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 5, pp 931–941

First Online: 08 March 2014Received: 16 September 2013Accepted: 23 February 2014DOI: 10.1007-s00280-014-2424-x

Cite this article as: Curtis, K.K., Sarantopoulos, J., Northfelt, D.W. et al. Cancer Chemother Pharmacol 2014 73: 931. doi:10.1007-s00280-014-2424-x

Abstract

PurposeTo conduct a phase I study determining the safety, pharmacokinetics and preliminary efficacy of EP-100, a novel anticancer drug consisting of natural luteinizing-hormone-releasing hormone LHRH ligand linked to a cationic membrane-disrupting peptide.

MethodsPatients with advanced, solid tumors, positive for LHRH receptor by immunohistochemistry IHC, received EP-100 weekly or twice weekly for 3 of 4 weeks in a 28 day cycle. A modified Fibonacci 3 + 3 dose-escalation schema was used. Initial cohorts received EP-100 once weekly cohorts 1–7, 0.6–7.8 mg-m, n = 21. Later cohorts received doses twice weekly cohorts 7–11, 7.8–40 mg-m, n = 16.

ResultsLHRH-receptor expression was confirmed by IHC in 52 of 89 consented patients; 37 patients received at least 1 dose. Cohorts receiving doses of 5.2 mg-m and above achieved therapeutic levels from in vitro studies Clearance was rapid mean half-life 7.1 ± 3.8 to 15.9 ± 3.6 min. The maximum-tolerated dose was not reached at the highest dose evaluated 40 mg-m twice weekly. Grade 2 increase in alanine aminotransferase-serum aspartate aminotransferase in one patient resolved, did not recur upon re-treatment, and was not observed in other patients. The only drug-related adverse event was transient infusion-related dermatologic reactions 10 patients. No complete or partial tumor responses were observed; seven patients had stable disease of 16 weeks.

ConclusionsEP-100 was well tolerated in patients with advanced, LHRH-receptor-expressing solid tumors. The recommended phase 2 dose is 40 mg-m twice weekly for 3 of 4 weeks per cycle.

KeywordsLHRH receptor EP-100 Cytolytic peptide Cytolytic peptide conjugate Advanced-metastatic solid tumors Electronic supplementary materialThe online version of this article doi:10.1007-s00280-014-2424-x contains supplementary material, which is available to authorized users.

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Author: Kelly K. Curtis - John Sarantopoulos - Donald W. Northfelt - Glen J. Weiss - Kerry M. Barnhart - John K. Whisnant - Car

Source: https://link.springer.com/







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