E7130

P1, N=95, Recruiting, Eisai Co., Ltd. | Trial completion date: Apr 2027 --> Jun 2025 | Trial primary completion date: Apr 2027 --> Jun 2025

P1, N=95, Recruiting, Eisai Co., Ltd. | Trial completion date: Apr 2026 --> Apr 2027 | Trial primary completion date: Apr 2026 --> Apr 2027

P1, N=95, Recruiting, Eisai Co., Ltd. | Trial completion date: Oct 2025 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2026

Overall, our findings strongly support the mechanism of action that E7130 alters the TME in therapeutically beneficial ways. Importantly, from a translational perspective, our data demonstrated MRI as a non-invasive biomarker to detect TME amelioration by E7130, supported by consistent changes in plasma biomarkers.

E7130 480 μg/m Q3W was chosen for the dose-expansion part over 300 μg/m Q2W primarily per dose-dependent biomarker results.

The vascular remodeling effect of E7130 increased ERα expression in cancer cells in vivo, and sensitized ER+ breast cancer against fulvestrant to achieve promising combinational anti-tumor activity. Our data provides compelling evidence that E7130 attenuates tumor malignancy by its tumor microenvironment ameliorating effects and improves current anti-cancer therapy in combination with other drugs.

Drug discovery using halichondrins was based on their outstanding in vivo antitumor (inhibitory) activity in mice and bone metastasis in mouse melanoma model first reported in 1996. From these results, we hypothesized that halichondrins are not simple microtubule-targeted compounds in tumor cell, and have developed E7130, which harbors unique tumor microenvironment ameliorating effects. Here we proved that E7130 impedes the TGF-β-induced myofibroblast transdifferentiation process without killing the fibroblast by disrupting microtubule network formation, which is important for focal adhesion assembly and thereby the downstream activation of the PI3K/AKT/mTOR pathway.

P1, N=140, Recruiting, Eisai Co., Ltd. | Trial completion date: Dec 2021 --> Mar 2023 | Trial primary completion date: Dec 2021 --> Mar 2023

P1, N=140, Recruiting, Eisai Co., Ltd. | Trial completion date: Mar 2023 --> Dec 2021 | Trial primary completion date: Mar 2023 --> Dec 2021

P1, N=140, Recruiting, Eisai Co., Ltd. | Trial completion date:Dec 2021 --> Mar 2023 | Trial primary completion date: Dec 2021 --> Mar 2023