Novel LHRH-receptor-targeted cytolytic peptide, EP-100: First-in-human phase I study in patients with advanced LHRH-receptor-expressing solid tumors

Kelly K. Curtis, John Sarantopoulos, Donald W. Northfelt, Glen J. Weiss, Kerry M. Barnhart, John K. Whisnant, Carola Leuschner, Hector Alila, Mitesh J. Borad, Ramesh K. Ramanathan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Purpose: To 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. Methods: Patients 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/m2, n = 21). Later cohorts received doses twice weekly (cohorts 7-11, 7.8-40 mg/m2, n = 16). Results: LHRH-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/m2 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/m2 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. Conclusions: EP-100 was well tolerated in patients with advanced, LHRH-receptor-expressing solid tumors. The recommended phase 2 dose is 40 mg/m2 twice weekly for 3 of 4 weeks per cycle.

Original languageEnglish (US)
Pages (from-to)931-941
Number of pages11
JournalCancer chemotherapy and pharmacology
Volume73
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • Advanced/metastatic solid tumors
  • Cytolytic peptide
  • Cytolytic peptide conjugate
  • EP-100
  • LHRH receptor

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Novel LHRH-receptor-targeted cytolytic peptide, EP-100: First-in-human phase I study in patients with advanced LHRH-receptor-expressing solid tumors'. Together they form a unique fingerprint.

Cite this