October 29, 2025--RAHWAY, N.J. & NUTLEY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Eisai today announced results from the Phase 3 LEAP-012 trial evaluating KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, plus LENVIMA® (lenvatinib), the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, in combination with transarterial chemoembolization (TACE) for the treatment of patients with unresectable, non-metastatic hepatocellular carcinoma (HCC).
At a pre-specified interim analysis, KEYTRUDA plus LENVIMA in combination with TACE did not achieve statistical significance for overall survival (OS), one of the study’s primary endpoints, compared to TACE alone. The likelihood of reaching the protocol-specified threshold for statistical significance for OS at a future analysis was evaluated by Merck and Eisai and considered to be low. On this basis, the study will be closed, and the companies are informing investigators of this decision. The safety profile of the KEYTRUDA plus LENVIMA-based regimen was consistent with that observed in previously reported studies evaluating the combination and in earlier analyses of LEAP-012. Further analysis of the data is ongoing; Merck and Eisai will work with investigators to share the results with the scientific community.
As reported previously, KEYTRUDA plus LENVIMA in combination with TACE met the study’s other primary endpoint of progression-free survival (PFS) and demonstrated a statistically significant and clinically meaningful improvement compared to TACE alone. Data from this first interim analysis, which served as the final analysis for the endpoint of PFS, were presented at the European Society for Medical Oncology (ESMO) Congress 2024 and published in The Lancet. With additional follow-up at subsequent analyses, PFS remained consistent.
“Although the progression-free survival results from this study are encouraging, unfortunately, the addition of KEYTRUDA plus LENVIMA to TACE did not show the overall survival benefit we hoped,” said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories. “We are grateful to the patients and investigators for their important contributions to this study, and our commitment is unwavering as we pursue new therapeutic options for people living with hepatocellular carcinoma, an aggressive and challenging-to-treat cancer.”
"The overall survival findings from LEAP-012, along with the previously reported improvement in progression-free survival, provide important insights for treating unresectable, non-metastatic hepatocellular carcinoma," said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai. "For years, TACE has been a standard of care for these patients, yet many experience disease progression within twelve months. With LEAP-012, we sought to make a meaningful difference for this patient population. LENVIMA continues to play an important role as a monotherapy treatment option for patients with unresectable HCC, and as a company with a deep heritage in liver cancer research, Eisai remains committed to advancing the science."
In June 2025, KEYTRUDA plus LENVIMA in combination with TACE was approved in China to treat unresectable non-metastatic HCC. KEYTRUDA plus LENVIMA is approved in the U.S., the European Union (EU), Japan and other countries for the treatment of advanced renal cell carcinoma (RCC) and certain types of advanced endometrial carcinoma. Lenvatinib is approved as KISPLYX for advanced RCC in the EU. Results from the LEAP-012 trial do not affect the current approved indications for the KEYTRUDA plus LENVIMA combination, including the approval of KEYTRUDA plus LENVIMA in combination with TACE in China to treat unresectable non-metastatic HCC.
LENVIMA monotherapy is approved for the treatment of patients with unresectable HCC in more than 80 countries and regions, including in the U.S., the EU, China and Japan.
KEYTRUDA is approved as a monotherapy for the treatment of patients with HCC secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen in the U.S. and as a monotherapy for the treatment of patients with HCC who have been previously treated with sorafenib or oxaliplatin-containing chemotherapy in China.
About LEAP-012
LEAP-012 is a multicenter, randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04246177) evaluating KEYTRUDA plus LENVIMA in combination with TACE versus dual placebo plus TACE for the treatment of patients with unresectable, non-metastatic HCC. The primary endpoints are PFS as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and OS. Secondary endpoints include objective response rate, duration of response, disease control rate and time to progression as assessed by BICR per above-mentioned RECIST v1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), PFS as assessed by BICR per mRECIST and safety. The study randomized 480 patients 1:1 to receive:
KEYTRUDA (400 mg intravenously [IV] every six weeks [Q6W]) plus LENVIMA (12 mg [for participants with screening body weight ≥60 kg] or 8 mg [for participants with screening body weight <60 kg] orally once a day) in combination with TACE (conducted as a background procedure of chemotherapeutic and embolic agents injected via hepatic artery 2-4 weeks after start of study intervention, and after the first tumor assessment scan and ≥1 month after the first TACE); or
IV placebo administered Q6W plus oral placebo administered once a day in combination with TACE.
All study drugs were continued until protocol-specified discontinuation criteria. KEYTRUDA was administered for up to two years (approximately 18 doses). After completing two years of combination therapy, LENVIMA may have been administered as a single agent until protocol-specified discontinuation criteria were met.
About hepatocellular carcinoma
Liver cancer is one of the leading causes of cancer-related deaths worldwide. In the U.S., the incidence rates of liver cancer have more than tripled since 1980, and death rates have doubled during that time. Incidence rates are expected to continue to rise in various regions across the world until 2040, including in countries with advanced healthcare systems. It is estimated there were more than 866,000 new cases of liver cancer and more than 758,000 deaths from the disease globally in 2022. In the U.S., it is estimated there will be approximately 42,240 patients diagnosed with liver cancer and 30,090 patient deaths from the disease in 2025. The five-year relative survival rate for liver cancer in the U.S. is 22% based on Surveillance, Epidemiology, and End Results (SEER) data from 2015-2021. Hepatocellular carcinoma is the most common type of liver cancer, accounting for an estimated 85% – 90% of primary liver cancer cases.
About KEYTRUDA® (pembrolizumab) injection for intravenous use, 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 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.
About KEYTRUDA® (pembrolizumab) injection for intravenous use, 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 the Merck and Eisai strategic collaboration
In March 2018, Eisai and Merck, known as MSD outside of 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 jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA.
Merck’s focus on cancer
Every 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.
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.
Eisai’s focus on cancer
Eisai positions Oncology as one of its key strategic areas, and aims to contribute to the cure of cancers through the discovery of innovative new drugs with new targets and mechanisms of action under the Deep Human Biology Learning (DHBL) drug discovery and development organization.
By utilizing biomarker data obtained from our products to elucidate the mechanisms of the incidence and root causes of cancer, as well as drug resistance, and using Eisai Group's precision chemistry technology to turn undruggable intracellular therapeutic targets into druggable ones, we will create new backbone therapeutic drugs.
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.