Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: Results of a phase 1 study

Raoul Tibes, Mitesh J Borad, Corina E. Dutcus, Larisa Reyderman, Kevie Feit, Andrew Eisen, David A. Verbel, Daniel D. Von Hoff

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: This phase 1 first-in-human study aimed to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and safety of E6201, and to establish recommended dosing in patients with advanced solid tumours, expanded to advanced melanoma. Methods: Part A (dose escalation): sequential cohorts received E6201 intravenously (IV) over 30 min (once-weekly [qw; days (D)1 + 8 + 15 of a 28-day cycle]), starting at 20 mg/m2, increasing to 720 mg/m2 or the MTD. Part B (expansion): patients with BRAF-mutated or wild-type (WT) melanoma received E6201 320 mg/m2 IV over 60 minutes qw (D1 + 8 + 15 of a 28-day cycle) or 160 mg/m2 IV twice-weekly (D1 + 4 + 8 + 11 + 15 + 18 of a 28-day cycle; BRAF-mutated only). Results: MTD in Part A (n = 25) was 320 mg/m2 qw, confirmed in Part B (n = 30). Adverse events included QT prolongation (n = 4) and eye disorders (n = 3). E6201 exposure was dose-related, with PK characterised by extensive distribution and fast elimination. One patient achieved PR during Part A (BRAF-mutated papillary thyroid cancer; 480 mg/m2 qw) and three during Part B (2 BRAF-mutated melanoma; 1 BRAF-WT melanoma; all receiving 320 mg/m2 qw). Conclusions: An intermittent regimen of E6201 320 mg/m2 IV qw for the first 3 weeks of a 28-day cycle was feasible and reasonably well-tolerated in patients with advanced solid tumours, including melanoma with brain metastases, with evidence of clinical efficacy.

Original languageEnglish (US)
Pages (from-to)1580-1585
Number of pages6
JournalBritish Journal of Cancer
Volume118
Issue number12
DOIs
StatePublished - Jun 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: Results of a phase 1 study'. Together they form a unique fingerprint.

  • Cite this