E7130 / Eisai, Harvard University - LARVOL DELTA

E7130's tumor microenvironment ameliorating activity enhances treatment efficacy in urothelial carcinoma. (AACR-NCI-EORTC 2025) - "These TME ameliorating activities of E7130 contributed to its significant combination efficacy with fulvestrant in ER+ breast cancer models, cetuximab in head and neck squamous cell carcinoma models, enzalutamide in castration-resistant prostate cancer models...The correlation between UC patient survival time and CAF-related gene expression was investigated using the TCGA database.Summary: E7130 demonstrated significantly stronger antitumor activity than gemcitabine and paclitaxel in UC xenograft models... E7130 demonstrated potent antitumor activity as monotherapy and in combination with gemcitabine and erdafitinib in UC xenograft models. Mechanistic analyses indicated that TME ameliorating effects of E7130 enhanced combination therapy efficacy by reducing αSMA-positive CAF and decreasing intratumoral hypoxic regions. These findings suggest that E7130 may be a promising antitumor agent and warrants further investigation."

Biomarker • Clinical • Tumor microenvironment • Breast Cancer • Castration-Resistant Prostate Cancer • Estrogen Receptor Positive Breast Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • CA9 • CD31 • PECAM1

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=62 | Completed | Sponsor: Eisai Co., Ltd. | N=95 ➔ 62 | Trial completion date: Jun 2026 ➔ Dec 2024 | Trial primary completion date: Jun 2026 ➔ Dec 2024 | Active, not recruiting ➔ Completed

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=95 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Novel tumor microenvironment ameliorator E7130 shows substantial combination efficacy with enzalutamide in a preclinical model of castration-resistant prostate cancer. (EORTC-NCI-AACR 2024) - P1 | "Previous preclinical studies have shown that through its TME ameliorating effects, E7130 has significant combination activity with antibody drugs (cetuximab, trastuzumab, anti-mPD-1 Ab, anti-PD-L1 Ab), antiestrogens (fulvestrant) and various cytotoxic agents...Gene expression profiles were compared among treatment groups by RNAseq analysis. In the CRPC LuCap96CR PDX model, E7130 showed significantly stronger antitumor activity compared to docetaxel... E7130 demonstrated potent antitumor activity as monotherapy and in combination with enzalutamide in a PDX model of CRPC. Mechanistic analyses indicated that TME ameliorating effects of E7130 contributed to its combination efficacy via effects on macrophages and endothelial cells. These data provide compelling evidence that E7130 is a promising anticancer agent in the new class of TME ameliorators."

IO biomarker • Preclinical • Tumor microenvironment • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD31 • PECAM1

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=95 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A large-scale study and six-month follow-up of an intervention to reduce causal illusions in high school students. (PubMed, R Soc Open Sci) - "2013 PLoS One 8, e71303 (doi:10.1371/journal.pone.0071303)), focusing on base rates, control conditions and confounding variables...Results showed medium-to-large and long-lasting effects on the reduction of causal illusions. To our knowledge, this is the first research showing the efficacy and long-term effects of a debiasing intervention against causal illusions that can be used on a large scale through the educational system."

Journal

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=95 | Recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Apr 2027 ➔ Jun 2025 | Trial primary completion date: Apr 2027 ➔ Jun 2025

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=95 | Recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Apr 2026 ➔ Apr 2027 | Trial primary completion date: Apr 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials. (PubMed, Org Lett) - "Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis."

Journal • Oncology

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=95 | Recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Oct 2025 ➔ Apr 2026 | Trial primary completion date: Apr 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Amelioration of Tumor-Promoting Microenvironment via Vascular Remodeling and CAF Suppression using E7130: Biomarker Analysis by Multi-modal Imaging Modalities. (PubMed, Mol Cancer Ther) - "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."

Biomarker • Journal • Oncology • Solid Tumor • CAFs • TGFB1

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. (PubMed, Cancer) - P1 | "E7130 480 μg/m Q3W was chosen for the dose-expansion part over 300 μg/m Q2W primarily per dose-dependent biomarker results."

Biomarker • Journal • Metastases • P1 data • Tumor microenvironment • Hematological Disorders • Leukopenia • Oncology • Solid Tumor • MMP9

Tumor microenvironment ameliorating effect of E7130 sensitized ER+ breast cancer against fulvestrant (AACR 2022) - P1 | "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."

Biomarker • Tumor microenvironment • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CD31 • ER

[VIRTUAL] First-in-human (FIH) study of E7130 in patients (pts) with advanced solid tumors: Primary result of dose-escalation part (ESMO 2021) - P1 | "E7130 had manageable toxicity in pts with advanced solid tumors, preliminary antitumor activity, and TME-related biomarker changes. E7130 480 μg/m2 Q3W was recommended for a further expansion part where safety, efficacy, PK, and biomarkers will be analyzed., Newtown, PA, USA."

Clinical • P1 data • Bladder Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Urothelial Cancer

Development of an analytical method to determine E7130 concentration in mouse plasma by micro-sampling using ultra-performance liquid chromatography-high resolution mass spectrometry. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "The calibration curve drawn was linear in the 0.2-100 ng/mL E7130 concentration range for mouse plasma microsamples (10 µL). Analytical results demonstrated good precision (<6.7%) and accuracy (88.5%-100.0%) in E7130 quantitation, indicating that UHPLC-HRMS is a useful method for pharmacokinetic analysis and a valuable approach for the quantitation of hardly fragmented compounds."

Journal • Preclinical • Oncology

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=95 | Recruiting | Sponsor: Eisai Co., Ltd. | Active, not recruiting ➔ Recruiting | N=65 ➔ 95 | Trial completion date: Apr 2024 ➔ Oct 2025

Enrollment change • Enrollment open • Trial completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

New Cluster Analysis Method for Quantitative Dynamic Contrast-Enhanced MRI Assessing Tumor Heterogeneity Induced by a Tumor-Microenvironmental Ameliorator (E7130) Treatment to a Breast Cancer Mouse Model. (PubMed, J Magn Reson Imaging) - "A two-dimensional cluster analysis might quantify the spatial distribution of a tumor subregion with a distinct range of K and v values."

Heterogeneity • Journal • Preclinical • Tumor microenvironment • Breast Cancer • Oncology • Solid Tumor

Editorial for "New Cluster Analysis Method for Quantitative DCE-MRI Assessing Tumor Heterogeneity Induced by E7130 Treatment to a Breast Cancer Mouse Model". (PubMed, J Magn Reson Imaging) - No abstract available

Heterogeneity • Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=65 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2023 ➔ Apr 2024 | Trial primary completion date: Mar 2023 ➔ Apr 2024

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1; N=65; Recruiting; Sponsor: Eisai Co., Ltd.; N=140 ➔ 65

Clinical • Enrollment change • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MRI

A landmark in drug discovery based on complex natural product synthesis. (PubMed, Sci Rep) - "According to these unique effects, E7130 significantly augment the effect of antitumour treatments in mouse models and is currently in a clinical trial. Overall, our work demonstrates that a total synthesis can address the issue of limited material supply in drug discovery/development even for the cases of complex natural products."

Journal • Oncology

[VIRTUAL] E7130 derived from total synthesis of halichondrin as a novel tumor-microenvironment ameliorator (AACR-II 2020) - "E7130 ameliorates the tumor microenvironment to improve cancer treatment when used in combination with other compounds. The data provide compelling evidence that E7130 is a promising molecular-targeting anticancer agent."

Biomarker • Tumor microenvironment • Oncology • CD31

[VIRTUAL] Magnetic resonance imaging detects perfusion and diffusion changes in response to a novel microenvironment ameliorator E7130 in a breast cancer model (AACR-II 2020) - "MRI can detect changes in the tumor microenvironment produced by E7130 before decrease in tumor sizes becomes apparent. E7130 may affect to the tumor microenvironment closely related to increase of tumor perfusion and diffusion of water molecules in the breast cancer lesion of the MCF-7 xenograft model."

Preclinical • Breast Cancer • Oncology • Solid Tumor • CAFs • MRI

[VIRTUAL] Mechanism of action analysis of anti-CAF activity of E7130, a novel tumor-microenvironment ameliorator (AACR-II 2020) - "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."

Biomarker • Tumor microenvironment • Melanoma • Oncology • Solid Tumor • CAFs • CD31

A Study of E7130 in Participants With Solid Tumors (clinicaltrials.gov) - P1; N=140; Recruiting; Sponsor: Eisai Co., Ltd.; Trial completion date: Dec 2021 ➔ Mar 2023; Trial primary completion date: Dec 2021 ➔ Mar 2023

Clinical • Trial completion date • Trial primary completion date