Eisai Co., Ltd. and MSD K.K. announced 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 hypoxia-inducible factor-2 alpha (HIF-2a) 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. 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. 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 PD-L1 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. 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 (PDGFRa), 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 cancer The 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 carcinoma The 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 carcinoma Renal 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 therapy Europe: 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 carcinoma The United States: The first-line treatment of adult patients with advanced renal cell carcinoma Europe: The first-line treatment of adult patients with advanced renal cell carcinoma Endometrial 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 chemotherapy The 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 radiation Europe: 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.
