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Eisai and Merck & Co., Inc., Rahway, NJ, USA Provide Update on
Two Phase 3 Trials Evaluating LENVIMA® (lenvatinib) Plus KEYTRUDA®
(pembrolizumab) in Patients With Certain Types ofMetastatic Non-Small Cell Lung Cancer

TOKYO and RAHWAY, N.J., Sept. 22, 2023 – Eisai (Headquarters: Tokyo, CEO: Haruo
Naito) and Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States andCanada) today provided updates on two Phase 3 trials, LEAP-006 and LEAP-008, evaluating
LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus
KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA in patients withcertain types of metastatic non-small cell lung cancer.
LEAP-006: The Phase 3 LEAP-006 trial evaluating LENVIMA plus KEYTRUDA in combination
with pemetrexed (Alimta®) and platinum-containing chemotherapy versus KEYTRUDA withpemetrexed and platinum-containing chemotherapy, a current standard of care option in thisdisease setting, as a first-line treatment for adult patients with metastatic, nonsquamous nonsmall cell lung cancer (NSCLC) who have confirmation that epidermal growth factor receptor(EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1)- directed therapies
are not indicated, did not meet its dual primary endpoints of overall survival (OS) and progressionfree survival (PFS). At the study’s final analysis, there was not an improvement in OS for patientstreated with KEYTRUDA plus LENVIMA with chemotherapy compared to KEYTRUDA withchemotherapy. Earlier interim analyses did not demonstrate a statistically significant improvement
in PFS or objective response rate (ORR), a key secondary endpoint.
LEAP-008: The Phase 3 LEAP-008 trial evaluating LENVIMA plus KEYTRUDA versus docetaxel,
a current second line standard of care option, as a treatment for patients with metastatic NSCLC
who progressed on or after platinum-containing chemotherapy and one prior anti-PD-1/-L1
immunotherapy, and have confirmation that EGFR-, ALK- or ROS1-directed therapies are not-1-

indicated, did not meet its dual primary endpoints of OS and PFS. At the final analysis of the study,
there was not an improvement in OS for patients who received KEYTRUDA plus LENVIMA
compared to docetaxel. Earlier interim analyses did not demonstrate a statistically significant
improvement in PFS or ORR, a key secondary endpoint.
In both the LEAP-006 and LEAP-008 trials, the safety profiles of the LENVIMA plus
KEYTRUDA-based treatment regimens were consistent with that observed in previously reported
studies evaluating the combination. A full evaluation of the data from these studies is ongoing.
The companies will work with investigators to share the results with the scientific community.
“As a leader in lung cancer research, we continue to try to advance science for our patientsby building upon the standard we set several years ago with KEYTRUDA,” said Dr. Gregory
Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories. “Whilethese results are not what we hoped for, we are proud of the foundational role that KEYTRUDA
has established in the treatment of certain types of lung cancer, and we are committed tocontinuing to research how we can further improve responses to our medicines for patients withdifficult-to-treat forms of the disease.”“Despite great progress in recent years, unmet needs still remain in the treatment ofpatients with metastatic non-small cell lung cancer, particularly for those without targetablebiomarkers,” said Dr. Corina Dutcus, Senior Vice President, Global Clinical Development,
Oncology at Eisai Inc. “KEYTRUDA plus LENVIMA has demonstrated survival benefit inadvanced renal cell carcinoma and advanced endometrial carcinoma, and while we aredisappointed that the final analyses of these non-small cell lung cancer studies did not show thesame benefit, we remain committed to applying learnings from these studies and furtheringresearch in oncology for people with unmet needs. We thank all the patients, their families andthe investigators involved.”
LENVIMA plus KEYTRUDA is approved in the U.S., the EU, Japan and other countries
for the treatment of advanced renal cell carcinoma (RCC) and certain types of advanced
endometrial carcinoma. Lenvatinib is marketed as KISPLYX® for advanced RCC in the EU. Eisai
and Merck & Co., Inc., Rahway, NJ, USA are studying the LENVIMA plus KEYTRUDA
combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various tumor
types, including but not limited to endometrial carcinoma, hepatocellular carcinoma, RCC, headand neck cancer, gastric cancer and esophageal cancer across multiple clinical trials.
Results from the LEAP-006 and LEAP-008 trials do not affect the current approved
indications for the LENVIMA and KEYTRUDA combination or other ongoing trials from the LEAP
clinical program.
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About LEAP-006
LEAP-006 is a randomized, placebo-controlled Phase 3 trial (ClinicalTrials.gov,
NCT03829319) evaluating LENVIMA plus KEYTRUDA with pemetrexed and platinum-containing
chemotherapy versus placebo plus KEYTRUDA with pemetrexed and platinum-containing
chemotherapy for the first-line treatment of adult patients with metastatic, nonsquamous NSCLC
who have confirmation that EGFR-, ALK- or ROS1-directed therapies are not indicated. The dual
primary endpoints are PFS, as assessed by blinded independent central review (BICR) per
Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST v1.1) modified to follow a
maximum of 10 target lesions and a maximum of 5 target lesions per organ, and OS. Secondary
endpoints include ORR and duration of response (DOR), as assessed by BICR per RECIST v1.1,
quality of life and safety. The study enrolled an estimated 748 patients who were randomized 1:1
to receive:•

LENVIMA (8 mg orally once daily) plus KEYTRUDA (200 mg intravenously [IV] on Day
1 of each three-week cycle [Q3W]) with pemetrexed 500 mg/m2 IV Q3W andcarboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m2 Q3W IV; or•

Placebo (oral capsule once daily) plus KEYTRUDA (200 mg IV Q3W) with pemetrexed
500 mg/m2 IV Q3W and carboplatin AUC5 or cisplatin 75 mg/m2 Q3W IV

All study drugs were continued until protocol-specified discontinuation criteria.
KEYTRUDA was administered for up to 35 cycles (approximately two years). After completing
two years of combination therapy, LENVIMA may have been administered as a single agent until
protocol-specified discontinuation criteria were met. Carboplatin or cisplatin was administered for
up to four cycles. The LEAP-006 study was conducted in collaboration with Eli Lilly and Company,
the makers of Alimta® (pemetrexed).

About LEAP-008
LEAP-008 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT03976375)
evaluating LENVIMA plus KEYTRUDA versus docetaxel for the treatment of patients withmetastatic NSCLC who progressed on or after platinum-containing chemotherapy and one prioranti-PD-1/-L1 therapy, and have confirmation that EGFR-, ALK- or ROS1-directed therapies are
not indicated. The trial’s dual primary endpoints are PFS, as assessed by BICR per RECIST v1.1)
modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ,-3-and OS. Secondary endpoints include ORR and DOR as assessed by BICR per RECIST v1.1,
quality of life and safety. The study enrolled an estimated 422 patients who were randomized
4:4:1 to receive:•

LENVIMA (20 mg orally once daily) plus KEYTRUDA (200 mg IV every three-weeks);or••Docetaxel (75 mg/m2 IV every three-weeks); or
LENVIMA (24 mg orally once daily).

KEYTRUDA was administered for up to 35 cycles (approximately two years) or until
protocol-specified discontinuation criteria were met. After completing two years of combination
therapy, LENVIMA may have been administered as a single agent until protocol-specified
discontinuation criteria were met.

About lung cancer
Lung cancer is the leading cause of cancer death worldwide. 1 In 2020 alone, there weremore than 2.2 million new cases and 1.8 million deaths from lung cancer globally.2 Non-small celllung cancer is the most common type of lung cancer in the U.S., accounting for about 81% of allcases. 3 In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is25%, which is a 21% improvement over the last five years.4 Improved survival rates are due, inpart, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgicalprocedures as well as the introduction of new therapies. 3 Early detection and screening remain
an important unmet need, as 44% of lung cancer cases are not found until they are advanced. 4
Only 5.8% of people in the U.S. who are eligible were screened for lung cancer in 2021. 4
About LENVIMA® (lenvatinib) 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 (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-4-

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 in over 80 countries including Japan, the United States, China, and countries in Europe
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 in over 80 countries including Japan, the United States, China, and countries in Europe
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
Thymic carcinoma
 Indication as monotherapy (Approved in Japan)
Japan: Unresectable thymic carcinoma
Renal cell carcinoma (In Europe, the agent was launched under the brand name Kisplyx®)
 Indication in combination with everolimus(Approved in over 65 countries including the United States, and countries in 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 priorvascular endothelial growth factor (VEGF) targeted therapy
 Indication in combination with KEYTRUDA (generic name: pembrolizumab)-5-

(Approved in over 45 countries including Japan, the United States, and countries in Europe andAsia)
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 [including conditional approval] in over 50 countries including Japan, the United States,
and countries in 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 (EC) that is
not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have diseaseprogression 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
About KEYTRUDA® (pembrolizumab) Injection, 100mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works byincreasing 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 andits ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells
and healthy cells.
Merck & Co., Inc., Rahway, NJ, USA has the industry’s largest immuno-oncology clinicalresearch 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 understandthe 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 Eisai and Merck & Co., Inc., Rahway, NJ, USA Strategic Collaboration
In March 2018, Eisai and Merck & Co., Inc., Rahway, NJ, USA, known as MSD outside
the United States and Canada, through an affiliate, entered into a strategic collaboration for the-6-

worldwide co-development and co-commercialization of LENVIMA. Under the agreement, thecompanies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy
and in combination with KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ,
USA.
In addition to ongoing clinical studies evaluating the LENVIMA plus KEYTRUDA
combination across several different tumor types, the companies have jointly initiated new clinicalstudies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating
the combination in various tumor types across multiple clinical trials.
Eisai’s Focus on Cancer
Eisai 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”, “proteostasis disruption”, “cell lineage and cell differentiation”, and“inflammation, hypoxia, oxidative stress and cell senescence” 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 theaim of contributing to the cure of cancers.

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 ofrelieving 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), isdemonstrated 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.), andconnect with us on Twitter (U.S. and global), LinkedIn (for global, U.S. and EMEA) and Facebook(global).
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Merck & Co., Inc., Rahway, NJ, USA’s Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help
people with cancer worldwide. At Merck & Co., Inc., Rahway, NJ, USA, the potential to bring newhope to people with cancer drives our purpose and supporting accessibility to our cancer
medicines is our commitment. As part of our focus on cancer, Merck & Co., Inc., Rahway, NJ,
USA is committed to exploring the potential of immuno-oncology with one of the largest
development programs in the industry across more than 30 tumor types. We also continue tostrengthen our portfolio through strategic acquisitions and are prioritizing the development ofseveral promising oncology candidates with the potential to improve the treatment of advanced
cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck & Co., Inc., Rahway, NJ, USA
For over 130 years, Merck & Co., Inc., Rahway, NJ, USA, known as MSD outside of theUnited States and Canada, has been inventing for life, bringing forward medicines and vaccines
for many of the world’s most challenging diseases in pursuit of our mission to save and improve
lives. We demonstrate our commitment to patients and population health by increasing access tohealth care through far-reaching policies, programs and partnerships. Today, Merck & Co., Inc.,
Rahway, NJ, USA continues to be at the forefront of research to prevent and treat diseases thatthreaten people and animals – including cancer, infectious diseases such as HIV and Ebola, andemerging animal diseases– as we aspire to be the premier

research-intensive

biopharmaceutical company in the world. For more information, visit www.merck.com and connect
with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Rahway, NJ, USA
This news release of Merck & Co., Inc., Rahway, NJ, USA (the “company”) includes“forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’s management and are subject to significant risks anduncertainties. There can be no guarantees with respect to pipeline candidates that the candidates
will receive the necessary regulatory approvals or that they will prove to be commerciallysuccessful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual
results may differ materially from those set forth in the forward-looking statements.

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Risks and uncertainties include but are not limited to, general industry conditions andcompetition; general economic factors, including interest rate and currency exchange rate
fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); theimpact of pharmaceutical industry regulation and health care legislation in the United States andinternationally; global trends toward health care cost containment; technological advances, newproducts and patents attained by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the company’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial instability of international economies andsovereign risk; dependence on the effectiveness of the company’s patents and other protections
for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory
actions.
The company undertakes no obligation to publicly update any forward-looking statement,
whether as a result of new information, future events or otherwise. Additional factors that could
cause results to differ materially from those described in the forward-looking statements can befound in the company’s Annual Report on Form 10-K for the year ended December 31, 2022 andthe company’s other filings with the Securities and Exchange Commission (SEC) available at the
SEC’s Internet site (www.sec.gov).
World Hearth Organization. “Lung cancer” Fact sheet.
https://www.who.int/news-room/fact-sheets/detail/lung-cancer .
2Hyuna S. et al. Global cancer statistics 2020. CA Cancer J Clin. 2021; 71: 209-249.
https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21660 .
3American Cancer Society. Cancer Facts＆Figures
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023cancer-facts-and-figures.pdf .
4
American Lung Association. “Key findings.” State of lung cancer.
https://www.lung.org/research/state-of-lung-cancer/key-findings .
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