RAHWAY - Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Eisai today announced the first presentation of results from the final analysis of the Phase 3 LEAP-002 trial investigating KEYTRUDA, Merck's anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, versus LENVIMA monotherapy as a first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).
Results are being presented during a proffered paper session at the European Society for Medical Oncology (ESMO) Congress 2022, being held in Paris, France and virtually from Sept. 9-13 (abstract #LBA34).
In the final analysis of the trial, there was a trend toward improvement for one of the study's dual primary endpoints, overall survival (OS), for patients treated with KEYTRUDA plus LENVIMA versus LENVIMA monotherapy; however, the results did not meet statistical significance per the pre-specified statistical plan (HR=0.84 [95% CI: 0.71-1.00]; p=0.0227). The median OS was 21.2 months (95% CI: 19.0-23.6) for KEYTRUDA plus LENVIMA and 19.0 months (95% CI: 17.2-21.7) for LENVIMA monotherapy. Additionally, treatment with KEYTRUDA plus LENVIMA resulted in a trend toward improvement in the trial's other dual primary endpoint of progression-free survival (PFS) versus LENVIMA monotherapy; however, the results did not meet the pre-specified threshold at the first interim analysis for statistical significance (HR=0.87 [95% CI: 0.73-1.02]; p=0.0466).
'The LEAP-002 trial reflects our research strategy to build on evolving standards of care to further improve outcomes for more people with unresectable hepatocellular carcinoma,' said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories. 'The median overall survival of 21.2 months seen with KEYTRUDA plus LENVIMA provides critical insights for further research into the potential role of this combination.'
'While the outcome is not what we had hoped, it is important for us to see that patients in the trial treated with LENVIMA monotherapy had a median overall survival of 19.0 months,' said Corina Dutcus, M.D., Senior Vice President, Clinical Research, Oncology at Eisai Inc. 'Findings from the LEAP-002 trial will not only help advance our understanding and application of KEYTRUDA plus LENVIMA across our clinical development program but will also provide physicians with additional information on LENVIMA monotherapy's use in unresectable hepatocellular carcinoma, where it is currently approved as a treatment option in multiple regions around the world, including the U.S., the European Union (EU), Japan and China.'
LENVIMA monotherapy is approved for the first-line treatment of patients with uHCC in the U.S., the EU and China and for patients with uHCC in Japan. The approval of LENVIMA was based on results of the Phase 3 REFLECT trial, which evaluated the efficacy and safety of LENVIMA versus sorafenib for the first-line treatment of patients with uHCC.
KEYTRUDA plus LENVIMA (marketed as KISPLYX for renal cell carcinoma [RCC] in the EU) is approved in the U.S., the EU and Japan for the treatment of certain types of advanced endometrial carcinoma and advanced RCC. Merck and Eisai are studying the KEYTRUDA plus LENVIMA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in multiple tumor types, including but not limited to endometrial carcinoma, HCC, melanoma, non-small cell lung cancer, RCC, head and neck cancer, colorectal cancer, gastric cancer and esophageal cancer, across more than 15 clinical trials.
About hepatocellular carcinoma (HCC)
Hepatocellular carcinoma is the most common type of primary liver cancer and the most rapidly increasing cause of cancer deaths in the United States. Hepatocellular carcinoma accounts for approximately 90% of primary liver cancers. It is estimated there were more than 905,000 new cases of liver cancer and more than 830,000 deaths from the disease globally in 2020, making it the sixth most frequently diagnosed cancer worldwide and one of the leading causes of cancer deaths around the world. In the United States, it is estimated there will be over 41,000 new cases of liver cancer and over 30,000 deaths from this disease in 2022. Risk factors for liver cancer include gender, ethnicity, chronic viral hepatitis (Hep-B or Hep-C) infection, cirrhosis, alcohol use and metabolic syndrome. Hepatocellular carcinoma, which is often diagnosed at an advanced stage, has a five-year survival rate of approximately 20% in the United States.
About KEYTRUDA (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
About LENVIMA (lenvatinib); available as 10 mg and 4 mg capsules
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). 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 (PDGFR), KIT, and RET. The combination of LENVIMA and everolimus showed increased anti-angiogenic and anti-tumor 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. 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.
About the Merck and Eisai strategic collaboration
In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck's anti-PD-1 therapy KEYTRUDA.
In addition to ongoing clinical studies evaluating the KEYTRUDA plus LENVIMA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in multiple tumor types across more than 15 clinical trials.
About Merck
At Merck, known as MSD 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.
About Eisai
Eisai'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.
Contact:
Melissa Moody
Tel: (215) 407-3536
MERCK & CO., INC. 
