During the upcoming European Society for Medical Oncology (ESMO) Congress in Berlin, Germany (October 17, – 21, 2025) Eisai is presenting results from its clinical research across the company’s oncology portfolio and pipeline.
One of the notable presentations is data from the Phase 3 Study 309/KEYNOTE-775 trial, which evaluated lenvatinib (Lenvima®; Eisai)*, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, in combination with the anti-PD-1 therapy pembrolizumab (Keytruda®; Merck & Co, known as Merck Sharp en Dohme/MSD outside of the United States and Canada), versus treatment of physician’s choice for patients with advanced endometrial carcinoma.[1]
The treatment of advanced and recurrent endometrial carcinoma remains a difficult due to the limited and ineffective treatment options following platinum and taxane based chemotherapy. Patients who are microsatellite stable (MSS) or mismatch repair proficient (pMMR) have even fewer effective therapies and poorer survival outcomes. Studies have confirmed that the combination of lenvatinib plus pembrolizumab is an effective treatment option for patients diagnosed with advanced and recurrent endometrial cancer who are MSS or pMMR who have failed prior platinum-based treatment.
The initial results of the Phase 3 Study 309/KEYNOTE-775 trial, funded by Eisai and Merck & Co, showed that lenvatinib in combination with pembrolizumab led to significantly longer progression-free survival (PFS) and overall survival (OS) than chemotherapy among patients with advanced endometrial cancer.[2][3] The presentation at this years ESMO Congress will feature 5-year overall survival data, providing deeper insights into long-term treatment for patients affected by this disease (NCT03517449; Abstract #1119P).
“The 5-year overall survival follow-up from Study 309/KEYNOTE-775 being presented at ESMO highlights the consistency of the study data over time, supporting the established role of lenvatinib plus pembrolizumab in the treatment of endometrial cancer and underscoring Eisai’s commitment to generating the long-term evidence that patients, families, and healthcare providers rely on to make informed treatment decisions,” noted Corina Dutcus, MD, Senior Vice President, Oncology Global Clinical Development Lead at Eisai.
“Our research in endometrial cancer, alongside our data in renal cell carcinoma and innovative pipeline approaches, reflects our dedication to our human health care concept to address unmet medical needs and advance treatment options for people living with cancer,” Dutcus added.
Further endometrial cancer research includes additional 1-year follow-up results from the Phase 3 LEAP-001 study in first-line advanced or recurrent endometrial carcinoma (NCT03884101; Abstract #1114P), as well as a combined analysis examining post-(neo)adjuvant therapy outcomes from both the Study 309/KEYNOTE-775 and LEAP-001 studies (Abstract #1124P).
In renal cell carcinoma (RCC), final analysis data from the CLEAR study comparing lenvatinib plus pembrolizumab versus sunitinib malate (Sutent®; Pfizer) in patients with advanced RCC with or without bone metastases will be presented (NCT02811861; Abstract #2603P). Initial results of the combination of lenvatinib plus pembrolizumab showed a consistent, durable benefit with a manageable safety profile in treatment-naïve patients with advanced RCC. [4]
E7386
Research from Eisai’s pipeline to be presented at the upcoming ESMO congress includes clinical and biomarker results from Study 102 evaluating E7386, a CREB-binding protein (CBP)/β-catenin interaction inhibitor, in combination with lenvatinib in patients with advanced or recurrent endometrial carcinoma (NCT04008797; Abstract #1153P).
E7386 is thought to block the protein-protein interaction between a transcriptional co-activator, cAMP response element-binding protein (CREB) binding protein (CBP) and β-catenin, resulting in the inhibition of Wnt / β-catenin pathway-dependent gene expression. Since E7386 is thought to act on the CBP / β-catenin transcription complex located at the most downstream of the Wnt signaling, it is expected to inhibit not only ligand-dependent activation but also activation caused by gene mutations in Wnt signaling factors such as adenomatous polyposis coli (APC) and β-catenin. E7386 is created through collaboration research between Eisai and PRISM BioLab.
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Note: * Lenvatinib (Lenvima®), discovered and developed by Eisai, is a multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRA), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2 alpha (FRS2) phosphorylation. In syngeneic mouse tumor models, the combination of lenvatinib with an anti-PD-1 monoclonal antibody decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity compared to either treatment alone. The combination of Lenvatinib and everolimus showed increased antiangiogenic and antitumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone.
Clinical trials
Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician’s Choice in Participants With Advanced Endometrial Cancer (MK-3475-775/E7080-G000-309 Per Merck Standard Convention [KEYNOTE-775]) – ClinicalTrials.gov ID NCT03517449
Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001) (LEAP-001) – ClinicalTrials.gov ID NCT03884101
Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma (CLEAR)
ClinicalTrials.gov ID NCT02811861
A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor – ClinicalTrials.gov ID NCT04008797
Highlights of prescribing information
Pembrolizumab (Keytruda®; Merck & Co/Merck Sharp en Dohme/MSD)[Prescribing Information
Lenvatinib (Lenvima®; Eisai)[Prescribing information]
Sunitinib malate (Sutent®; Pfizer)[Prescribing Information]
Everolimus (Afinitor®; Novartis)[Prescribing Information]
Reference
[1] Walker CA, Spirtos AN, Miller DS. Pembrolizumab plus lenvatinib combination therapy for advanced endometrial carcinoma. Expert Rev Anticancer Ther. 2023 Apr;23(4):361-368. doi: 10.1080/14737140.2023.2194634. Epub 2023 Mar 28. PMID: 36944439.
[2] Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. doi: 10.1056/NEJMoa2108330. Epub 2022 Jan 19. PMID: 35045221; PMCID: PMC11651366.
[3] Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. doi: 10.1200/JCO.22.02152. Epub 2023 Apr 14. PMID: 37058687; PMCID: PMC10414727.
[4] Motzer RJ, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Alekseev B, Rha SY, Merchan J, Goh JC, Lalani AA, De Giorgi U, Melichar B, Hong SH, Gurney H, Méndez-Vidal MJ, Kopyltsov E, Tjulandin S, Gordoa TA, Kozlov V, Alyasova A, Winquist E, Maroto P, Kim M, Peer A, Procopio G, Takagi T, Wong S, Bedke J, Schmidinger M, Rodriguez-Lopez K, Burgents J, He C, Okpara CE, McKenzie J, Choueiri TK; CLEAR Trial Investigators. Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study. J Clin Oncol. 2024 Apr 10;42(11):1222-1228. doi: 10.1200/JCO.23.01569. Epub 2024 Jan 16. PMID: 38227898; PMCID: PMC11095851.
Featured image: © 2019 – 2025 General images of ESMO 2019 Congress held in Barcelona, Spain, Courtesy European Society for Medical Oncology (ESMO). Used with Permission.
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