First-in-human study of E7130 (a tumor microenvironment-ameliorating microtubule inhibitor) in patients with advanced solid tumors: Primary results of the dose-escalation part

BackgroundE7130 is a novel anticancer agent created from a total synthetic study of norhalichondrin B. The authors report the E7130 dose-escalation part of a first-in-human study of patients with advanced solid tumors (NCT03444701). MethodsJapanese patients >= 20 years of age were enrolled. E7130 was administered intravenously in two cycles: day 1 of a 21-day cycle (Q3W) or days 1 and 15 of a 28-day cycle (Q2W). Doses were escalated from 270 to 550 mu g/m(2) for the Q3W group or 25-400 mu g/m(2) for the Q2W group. The primary end point of the dose-escalation phase was safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs) and adverse events. Other end points included determination of the maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics. ResultsForty-four patients were enrolled: 15 in the E7130 Q3W group and 29 in the Q2W group. Treatment-emergent adverse events (TEAEs) occurred in all patients; the most common TEAE overall was leukopenia (78.6%). Grade 3-4 TEAEs occurred in 93.3% of patients in the Q3W group and 86.2% of patients in the Q2W group. None had a TEAE resulting in study drug discontinuation, and no treatment-related deaths were reported. Per the DLT evaluation, the MTDs were determined as 480 mu g/m(2) Q3W and 300 mu g/m(2) Q2W. Significant changes in multiple plasma biomarkers, including vascular endothelial growth factor 3 and matrix metallopeptidase 9, were dose-dependent after initial doses of 350-480 mu g/m(2). ConclusionsE7130 480 mu g/m(2) Q3W was chosen for the dose-expansion part over 300 mu g/m(2) Q2W primarily per dose-dependent biomarker results.

Automated summary

This study reported the dose-escalation part of a first-in-human clinical trial of the synthetic anticancer agent E7130. The results showed that the 480 mu g/m(2) Q3W dose of E7130 had better tolerability and efficacy, and was chosen as the treatment dose for the dose-expansion part.