Application Submitted for LENVIMA(R) (lenvatinib) in Japan Seeking Approval of Additional Dosage and Administration for Combination with WELIREG(R) (belzutifan) for Renal Cell Carcinoma that has Progressed After Chemotherapy
TOKYO, Mar 27, 2026 - (JCN Newswire via SeaPRwire.com) - Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and MSD K.K. (Headquarters: Tokyo, Representative Director: Prashant Nikam, “MSD”), a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, announced today that an application for LENVIMA® (lenvatinib), an orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, has been submitted in Japan for the additional dosage and administration in combination with WELIREG® (belzutifan), the first-in-class oral hypoxiainducible factor-2 alpha (HIF-2α) inhibitor from MSD, for the treatment of unresectable or metastatic renal cell carcinoma that has progressed after chemotherapy.This application is based on the results of the Phase 3 LITESPARK-011 trial evaluating the dual regimen of LENVIMA plus WELIREG for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease progressed on or after treatment with anti-programmed death receptor-1 (PD-1)/ programmed death-ligand 1 (PD-L1) therapy. The data from this trial were presented at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium in February 2026. At a pre-specified interim analysis with a median follow-up of 29.0 months (range, 19.3-49.2), the LENVIMA plus WELIREG combination therapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), one of the primary endpoints, reducing the risk of disease progression or death by 30% (HR=0.70 [95% CI, 0.59-0.84]; p=0.00007) compared to cabozantinib. The safety profile of this combination was consistent with those reported for each agent administered as monotherapy, and no new safety signals were identified.In 2022, approximately 435,000 people worldwide were newly diagnosed with kidney cancer, and about 156,000 people died from the disease. 1 In Japan, it is estimated that roughly 21,000 people were newly diagnosed and about 7,000 died in 2022.2 RCC accounts for approximately 85% of kidney cancers3, and the five-year survival rates for patients with stage III and IV RCC have been reported as 63%–78% and 27%–28%4, respectively, indicating that the disease still has a high unmet medical needs.LENVIMA is approved in combination with KEYTRUDA ® (pembrolizumab) in Japan for the first-line treatment of unresectable or metastatic RCC. WELIREG is approved in Japan for the treatment of unresectable or metastatic RCC that has progressed following cancer chemotherapy. Additionally, supplemental New Drug Applications (sNDA) for the LENVIMA and WELIREG combination therapy for the treatment of adult patients with advanced RCC with a clear cell component following a PD-1 or PDL1 inhibitor has been accepted by the U.S. Food and Drug Administration (FDA), with a PDUFA (Prescription Drug User Fee Act) target action date set for October 4, 2026.Eisai and MSD have been collaborating through the provision of information on LENVIMA in Japan since October 2018, and will work together to expedite the maximization of contribution to patients with cancer.About LENVIMA (lenvatinib)LENVIMA, discovered and developed by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA 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 (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone. LENVIMA has been approved for the indications below.Thyroid cancer- Indication as monotherapy(Approved mainly in Japan, the United States, Europe, China and Asia)Japan: Unresectable thyroid cancerThe United States: The treatment of patients with locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer (DTC)Europe: The treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI)Hepatocellular carcinoma- Indication as monotherapy(Approved mainly in Japan, the United States, Europe, China and Asia)Japan: Unresectable hepatocellular carcinomaThe United States: The first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)Europe: The treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy- Indication in combination with KEYTRUDA (generic name: pembrolizumab) and transarterial chemoembolization (Approved in China)Thymic carcinoma- Indication as monotherapy (Approved in Japan)Japan: Unresectable thymic carcinomaRenal cell carcinoma (In Europe other than the United Kingdom, the agent was launched under the brand name Kisplyx®)- Indication in combination with everolimus(Approved mainly in the United States, Europe and Asia) The United States: The treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapyEurope: The treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor (VEGF) targeted therapy- Indication in combination with KEYTRUDA(Approved mainly in Japan, the United States, Europe and Asia)Japan: Radically unresectable or metastatic renal cell carcinomaThe United States: The first-line treatment of adult patients with advanced renal cell carcinomaEurope: The first-line treatment of adult patients with advanced renal cell carcinomaEndometrial carcinoma- Indication in combination with KEYTRUDA(Approved mainly in Japan, the United States, Europe and Asia)Japan: Unresectable, advanced or recurrent endometrial carcinoma that progressed after cancer chemotherapyThe United States: The treatment of patients with advanced endometrial carcinoma that is pMMR or not microsatellite instability-high (MSI-H), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiationEurope: The treatment of adult patients with advanced or recurrent endometrial carcinoma (EC) who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and are not candidates for curative surgery.About WELIREG (belzutifan)WELIREG, Merck & Co., Inc., Rahway, NJ, USA’s, known as MSD outside of the United States and Canada, first-in-class hypoxia-inducible factor 2 alpha (HIF-2α) inhibitor, is an orally administered small-molecule designed to reduce transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis and tumor growth. By inhibiting HIF-2α signaling, WELIREG aims to disrupt key pathways certain tumors may use to adapt to low-oxygen conditions, including those that help promote abnormal blood vessel formation and support tumor survival. WELIREG has demonstrated antitumor activity in certain von Hippel-Lindau (VHL) diseaseassociated tumors, renal cell carcinoma and in pheochromocytoma or paraganglioma. As part of a broader clinical program, Merck & Co., Inc., Rahway, NJ, USA continues to research WELIREG monotherapy and combination approaches for people with genitourinary, breast and gynecologic cancers across a range of treatment settings to further define where HIF-2α inhibition may provide clinical benefit and to better understand which patients are most likely to respond. WELIREG has been approved in Japan for the treatment of certain von Hippel–Lindau (VHL) disease–associated tumors, as well as for unresectable or metastatic renal cell carcinoma that has progressed after chemotherapy.LITESPARK-011 ResultsData from LITESPARK-011 (ClinicalTrials.gov, NCT04586231) were presented at the ASCO GU Symposium held in February 2026. LITESPARK-011 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT04586231) evaluating WELIREG in combination with LENVIMA compared to cabozantinib for the treatment of patients with advanced clear cell RCC that has progressed on or after anti-PD-1/L1 therapy. The dual primary endpoints are progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by blinded independent central review (BICR), and overall survival (OS). Secondary endpoints include objective response rate (ORR) per RECIST v1.1 as assessed by BICR, duration of response (DOR) per RECIST v1.1 as assessed by BICR, and safety. The trial enrolled 747 patients who were randomized to receive WELIREG (120 mg orally once daily) plus LENVIMA (20 mg orally once daily) or cabozantinib (60 mg orally once daily).At a pre-specified second interim analysis with a median follow-up of 29.0 months (range, 19.3- 49.2), WELIREG plus LENVIMA demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of PFS, reducing the risk of disease progression or death by 30% (HR=0.70 [95% CI, 0.59-0.84]; p=0.00007) compared to cabozantinib. For WELIREG plus LENVIMA, the median PFS was 14.8 months (95% CI, 11.2-16.6) versus 10.7 months (95% CI, 9.2-11.1) for cabozantinib. A trend toward improvement in overall survival (OS), the trial’s other primary endpoint, was also observed for WELIREG plus LENVIMA (HR=0.85 [95% CI, 0.68-1.05]; p=0.06075). The median OS was 34.9 months (95% CI, 27.5-NR) for WELIREG plus LENVIMA versus 27.6 months (95% CI, 24.0-31.4) for cabozantinib. The trial is continuing, and OS will be evaluated at a subsequent analysis per the clinical trial protocol. Regarding secondary endpoints, at the first interim analysis with a median follow-up of 19.6 months (range, 9.9-39.8), WELIREG plus LENVIMA met ORR, demonstrating a statistically significant improvement compared to cabozantinib. A confirmed ORR of 52.6% (95% CI, 47.3-57.7) was observed for WELIREG plus LENVIMA versus 39.6% (95% CI, 34.6-44.8) for cabozantinib. At the second interim analysis with a median follow-up of 29.0 months, the median DOR was 23.0 months (95% CI, 2.0-44.3+) for WELIREG plus LENVIMA versus 12.3 months (95% CI, 1.8+-35.9+) for cabozantinib. WELIREG plus LENVIMA was administered to 370 patients and cabozantinib was administered to 371 patients. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 71.6% of patients receiving WELIREG plus LENVIMA versus 65.8% of patients receiving cabozantinib. Adverse events led to treatment discontinuation in 11.1% of patients receiving WELIREG plus LENVIMA and in 11.3% of patients receiving cabozantinib, respectively. Serious adverse events were observed in 51.6% of patients receiving WELIREG plus LENVIMA versus 43.9% of patients receiving cabozantinib, and AEs led to death in 5.4% of patients (two were treatment-related: thrombotic microangiopathy [n=1] and pneumonitis [n=1]) versus 3.2% (one was treatment-related: hemoptysis [n=1]) of patients, respectively.About the Eisai and Merck & Co., Inc., Rahway, NJ, USA Strategic CollaborationIn March 2018, Eisai and Merck & Co., Inc., Rahway, NJ, USA through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck & Co., Inc., Rahway, NJ, USA’s anti-PD-1 therapy, KEYTRUDA, and HIF-2α inhibitor, WELIREG.Eisai’s focus on cancerEisai acknowledges “Oncology” as one of its key strategic areas, and will continue to focus on the discovery and development of anti-cancer drugs within drug discovery domains including “microenvironment”, “protein integrity and homeostasis”, and “cell lineage and cell differentiation” under the Deep Human Biology Learning (DHBL) drug discovery and development organization. Eisai aspires to discover innovative new drugs with new targets and mechanisms of action from these domains, with the aim of contributing to the cure of cancers.6. About EisaiEisai’s Corporate Concept is “to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides.” Under this Concept [also known as our human health care (hhc) Concept], we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.In addition, our continued commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), is demonstrated by our work on various activities together with global partners. For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), us.eisai.com (for U.S. headquarters: Eisai Inc.) or www.eisai.eu (for Europe, Middle East, Africa, Russia, Australia, and New Zealand headquarters: Eisai Europe Ltd.), and connect with us on X (U.S. and global), LinkedIn (for U.S. and EMEA) and Facebook (global).Merck & Co., Inc., Rahway, NJ, USA’s Focus on CancerEvery day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncologyAbout MSDAt MSD (the name by which Merck & Co., Inc., Rahway, NJ, USA, is known outside of the United States and Canada), we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.msd.co.jp and connect with us on Facebook, Twitter, and YouTube.Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, et al. (2024) Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/media/globocan/factsheets/cancers/29-kidney-fact-sheet.pdf, accessed 27 Mar 2026.Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, et al. (2024) Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer, Available from: https://gco.iarc.who.int/media/globocan/factsheets/populations/392-japan-fact-sheet.pdf, accessed 27 Mar 2026.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer. 2025; 2026 Version 1. Rose TL and Kim WY. Renal cell carcinoma: a review. JAMA. 2024 Sep 24;332(12):1001– 10.Media InquiriesEisai Co., Ltd.Public Relations DepartmentTEL: +81 (0)3-3817-5120MSD K.K.Communications DivisionTatsuro MuraseTEL: +81 (0)70-8700-0112 Copyright 2026 JCN Newswire via SeaPRwire.com. All rights reserved. www.jcnnewswire.com
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