Eisai and PRISM BioLab's novel CBP/β-catenin inhibitor E7386, in combination with lenvatinib, has demonstrated promising antitumor activity in patients with advanced endometrial cancer who progressed following standard treatments, according to data to be presented at the upcoming American Society of Clinical Oncology (ASCO) Congress 2025.
The open-label Phase Ib study (NCT04008797) completed enrollment of 30 patients with advanced endometrial cancer who had previously progressed following platinum-based chemotherapy and anti-PD-(L)1 immunotherapy. By the data cutoff date of October 22, 2024, nine patients (30%) showed confirmed responses, defined as tumor size reduction exceeding 30%, resulting in an overall response rate of 30.0%.
Notably, the efficacy was even more pronounced in patients without prior lenvatinib treatment, with an overall response rate of 42.9% in this subgroup. At the time of data cutoff, nine patients were still receiving treatment.
Mechanism of Action and Development History
E7386 represents an innovative approach to cancer treatment as an orally available small molecule that inhibits protein-protein interactions between the transcription factor CBP and β-catenin, thereby regulating Wnt signaling—a pathway frequently dysregulated in cancer.
The compound was developed through collaborative research between Eisai and PRISM BioLab, a biotechnology company specializing in small molecule inhibitors of protein-protein interaction targets. E7386 achieved clinical proof of concept in October 2021 and is currently being evaluated in multiple clinical studies.
Dr. Takashi Owa, Chief Scientific Officer at Eisai, commented, "These results are particularly encouraging for endometrial cancer patients who have limited treatment options after progression on standard therapies. The combination of E7386 with lenvatinib appears to offer a novel mechanism that may overcome resistance to existing treatments."
Study Design and Patient Population
The trial was designed to determine the optimal dose of E7386 in combination with lenvatinib, a multi-kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs), among other receptor tyrosine kinases.
The study has been implemented by Eisai across multiple countries including Japan, Korea, Taiwan, the United States, and France. Its primary objectives include determining the safety profile and recommended Phase 2 dose, while also evaluating pharmacokinetics and efficacy.
"Completing the enrollment of the dose expansion cohort has confirmed the promising preliminary antitumor activity of E7386 combined with lenvatinib, with a manageable safety profile," said Dr. Kenichi Nomoto, President of PRISM BioLab. "These results support the continued development of this combination therapy."
Current Treatment Landscape for Endometrial Cancer
Endometrial cancer is the most common gynecologic malignancy in developed countries, with limited treatment options for patients who progress after first-line therapy. Lenvatinib, in combination with pembrolizumab, is already approved for endometrial cancer, but resistance eventually develops in many patients.
The addition of E7386, with its distinct mechanism targeting the Wnt pathway, represents a potential strategy to overcome resistance mechanisms and improve outcomes for these patients.
Next Steps in Clinical Development
Following the completion of the dose expansion cohort, Eisai has initiated enrollment for the dose-optimization phase of the study in advanced endometrial cancer. This phase aims to further refine the dosing regimen to maximize efficacy while maintaining a favorable safety profile.
In addition to the combination with lenvatinib, E7386 is also being evaluated in other clinical studies, including as a monotherapy for solid tumors and in combination with pembrolizumab, an anti-PD-1 antibody from Merck & Co.
The full results from this study will be presented at the ASCO Congress 2025, scheduled to take place in Chicago from May 30 to June 3, 2025, providing the medical community with more detailed insights into this promising therapeutic approach.
