"Targeted + Immunotherapy"! Merck & Eisai's Keytruda + Lenvima Under EMA Review for Advanced Renal Cell Carcinoma and Endometrial Carcinoma

March 31, 2021 News /BioValleyBIOON/ -- Merck & Co. and its partner Eisai recently announced that the European Medicines Agency (EMA) has accepted two applications for the combination regimen of the anti-PD-1 therapy Keytruda (brand name: Keytruda; generic name: pembrolizumab) and the oral multi-receptor tyrosine kinase inhibitor Lenvima (brand name: Lenvima; generic name: lenvatinib): for the treatment of advanced renal cell carcinoma (RCC) and advanced endometrial cancer (EC).

The application for the Keytruda + Lenvima regimen in the treatment of advanced RCC is based on data from the pivotal Phase 3 CLEAR study (KEYNOTE-581/Study 307). The results of this study were presented in February this year at the 2021 American ClinicalTumorPresented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU 2021) and simultaneously published in The New England Journal of Medicine.

The CLEAR study evaluated the efficacy of Keytruda plus Lenvima as first-line treatment in patients with advanced renal cell carcinoma (RCC), comparing it with the Lenvima plus everolimus regimen and the sunitinib regimen. The results demonstrated that, compared with sunitinib, Keytruda plus Lenvima yielded statistically significant and clinically meaningful improvements in the primary endpoint of progression-free survival (PFS) as well as in the key secondary endpoints of overall survival (OS) and objective response rate (ORR). The safety profile of the Keytruda plus Lenvima combination in this study was generally consistent with that reported in previous studies.

Kidney Cancer (Image source: vecteezy.com)

The application for the Keytruda + Lenvima regimen in the treatment of advanced endometrial cancer is based on data from the pivotal Phase 3 KEYNOTE-775/Study 309 (NCT03517449). The study results were presented in mid-March this year at the 52nd Annual Meeting of the Society of Gynecologic Oncology (SGO) in 2021.Tumorpresented at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women's Cancer.

This trial evaluated the efficacy and safety of the Keytruda plus Lenvima regimen in patients with advanced, metastatic, or recurrent endometrial cancer who had experienced disease progression following platinum-based chemotherapy. The results demonstrated that, compared with chemotherapy, the Keytruda plus Lenvima regimen yielded statistically significant and clinically meaningful improvements in the primary endpoints of overall survival (OS) and progression-free survival (PFS), as well as in the secondary endpoint of objective response rate (ORR). In this study, the safety profile of the Keytruda and Lenvima combination was generally consistent with that reported in previous studies.

Endometrial Cancer (Image source: womenworking.com)

It is estimated that in 2020, there were over 430,000 newly diagnosed cases of kidney cancer worldwide, with nearly 180,000 deaths attributed to the disease. In Europe, in 2020, newDiagnosisThere were over 138,000 cases of kidney cancer and more than 54,000 deaths. Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for approximately 90% of all kidney cancer cases. About 30% of RCC patients have metastatic disease at diagnosis, and up to 40% of patients develop metastasis after surgical treatment for localized RCC.

It is estimated that in 2020, worldwide newDiagnosisThere were over 417,000 cases of uterine corpus cancer, with nearly 97,000 deaths. In Europe, there were over 130,000 new cases in 2020, and more than 29,000 deaths. Endometrial cancer (EC) is the most common type of uterine corpus cancer. It is believed that over 90% of uterine corpus cancers originate in the endometrium.。

Disease Survival Rate byDiagnosisThe 5-year survival rates for metastatic RCC and metastatic EC are 12% and 17%, respectively, varying by stage at diagnosis. The prognosis for both diseases is poor.

The Keytruda + Lenvima combination therapy is part of the strategic oncology collaboration between MSD and Eisai. In March 2018, the two companies signed a collaboration agreement worth up to $5.8 billion to develop Lenvima as monotherapy and in combination with Keytruda for multiple typesTumortreatment.

Lenvima is an oral multi-receptor tyrosine kinase (RTK) inhibitor with a novel binding mode, inhibiting not only those involved in tumor angiogenesis, tumor progression, andTumorIn addition to other receptor tyrosine kinases (RTKs) involved in immunomodulatory, pro-angiogenic, and oncogenic signaling pathways—including platelet-derived growth factor (PDGF) receptors PDGFRα, KIT, and RET—it can also selectively inhibit the kinase activity of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2, VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3, FGFR4).

Keytruda is an anti-PD-1 tumor immunotherapy that helps detect and combat tumor cells by enhancing the capability of the human immune system. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activatingTumorT lymphocytes of cells and healthy cells.

Currently, MSD and Eisai are advancing the LEAP (Lenvatinib and Pembrolizumab) clinical development program across 13 different types of tumors (endometrial cancer, hepatocellular carcinoma,Melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, urothelial carcinoma, cholangiocarcinoma, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer, and triple-negativeBreast Cancer) 20 itemsClinical Trialcontinue to study the Keytruda + Lenvima combination in China. Data from this project show that the Keytruda + Lenvima combination has been used in various typesTumordemonstrated robust efficacy! (Bioon.com)

Original Source: European Medicines Agency Accepts the Marketing Authorisationapplications For Two Additional Indications Of Anti Cancer Agent Lenvatinib In Combination With Pembrolizumab As A Treatment For Advanced Renal Cell Carcinoma And Advanced Endometrial Carcinoma