Study of Lenvatinib (MK-7902/E7080) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care in Participants With Metastatic Colorectal Cancer (MK-7902-017/E7080-G000-325/LEAP-017)

NCT ID: NCT04776148

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 563 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-29
• Study Completion Date: 2024-09-27

Brief Summary

The purpose of this study is to assess the safety and efficacy of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in participants with metastatic colorectal cancer. The study will also compare lenvatinib plus pembrolizumab with the standard of care treatment of regorafenib and TAS-102 (trifluridine and tipiracil hydrochloride).

The primary study hypothesis is that lenvatinib plus pembrolizumab is superior to standard of care with respect to overall survival.

Detailed Description

The Global portion, or Global Cohort, will include all participants who are enrolled during the Global enrollment period and will be the primary analysis population for the study. After enrollment of the global portion of the study is complete, the study will remain open to enrollment in China alone until the target number of participants from China have been enrolled to meet local regulatory requirements.

The China Cohort will include both participants enrolled in China for the Global Cohort plus those participants enrolled in China as part of the China extension enrollment period.

Per the supplemental Statistical Analysis Plan (sSAP), China participants randomized after the enrollment of the global portion is closed as part of the China extension enrollment period will not be included in the global analysis populations.

As pre-specified in the protocol, safety and efficacy outcome measures for the China Cohort will be analyzed separately from the Global Cohort.

Conditions

Colorectal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

lenvatinib+pembrolizumab

Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: DRUG

IV infusion

lenvatinib

Intervention Type: DRUG

oral capsule

standard of care treatment (regorafenib OR TAS-102)

Participants receive regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.

Group Type: ACTIVE_COMPARATOR

regorafenib

Intervention Type: DRUG

oral tablet

TAS-102 (trifluridine and tipiracil)

Intervention Type: DRUG

oral tablet

Interventions

pembrolizumab

IV infusion

Intervention Type: DRUG

lenvatinib

oral capsule

Intervention Type: DRUG

regorafenib

oral tablet

Intervention Type: DRUG

TAS-102 (trifluridine and tipiracil)

oral tablet

Intervention Type: DRUG

Other Intervention Names

KEYTRUDA®; MK-3475; MK-7902; E7080; STIVARGA®; REGONIX®; LONSURF®

Eligibility Criteria

Inclusion Criteria

• Has histologically or cytologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma (Stage IV A, B and C as defined by American Joint Committee on Cancer [AJCC] 8th edition). Note: Tumor must be determined to be NOT microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) by local testing
• Has been previously treated for their disease and has shown disease progression as defined by RECIST 1.1 on or after or could not tolerate standard treatment, which must include ALL of the following agents if approved and locally available in the country where the participant is randomized:

1. fluoropyrimidine, irinotecan and oxaliplatin

2. with or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (bevacizumab)

3. with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for RAS (KRAS/NRAS) wild-type (WT) participants

4. BRAF inhibitor (in combination with cetuximab +/- binimetinib) for BRAF V600E mutated metastatic colon cancer (mCRC)

• Has measurable disease per RECIST 1.1 assessed by the investigator
• Has provided to a designated central laboratory an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion which has not been previously irradiated
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days prior to randomization
• Has a life expectancy of at least 3 months, based on the investigator assessment
• Has the ability to swallow capsules or ingest a suspension orally or by a feeding tube
• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 millimeter of mercury (mmHg) with no change in antihypertensive medications within 1 week prior to randomization
• Male participants must agree to the following during the treatment period and for at least 90 days after the last dose of regorafenib or TAS-102 and at least 7 days after the last dose of lenvatinib: refrain from donating sperm PLUS either be abstinent from heterosexual intercourse as their preferred and usual lifestyle or use contraception. The male contraception period should continue for at least 7 days after discontinuation of lenvatinib
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a highly-effective contraceptive method during the treatment period and for at least 30 days after the last dose of lenvatinib, 120 days after the last dose of pembrolizumab, and 180 days after the last dose of regorafenib or TAS-102 (whichever is last) AND agrees not to donate eggs (ova, oocytes)
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study treatment

Exclusion Criteria

• Has a tumor that is microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) per local testing
• Has presence of gastrointestinal condition, eg, malabsorption, that might affect the absorption of study drug.
• Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
• Has radiographic evidence of encasement or invasion of a major blood vessel invasion or of intratumoral cavitation. In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta
• Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.

Participants with cardiac failure NYHA Class II, III and IV are not allowed to be assigned to the regorafenib in Arm B

• Has a history of arterial thromboembolism within 12 months of start of study drug
• Has urine protein ≥1 gram/24 hour
• Has prolongation of QT interval corrected with Fridericia's formula (QTcF interval) to >480 milliseconds
• Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with certain exceptions
• Has serious nonhealing wound, ulcer or bone fracture
• Has had major surgery within 3 weeks prior to first dose of study treatment
• Has received biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry
• Has preexisting ≥Grade 3 gastrointestinal or nongastrointestinal fistula
• Has received prior treatment with a combination of an anti-PD-1, anti-PD-L1, or anti PD-L2 agent with anti-VEGF monoclonal antibodies or vascular endothelial growth factor receptor (VEGFR) inhibitors
• Has previously received regorafenib or TAS-102
• Has received prior systemic anti-cancer therapy including investigational agents within 28 days prior to randomization
• Has received prior radiotherapy within 2 weeks of start of study treatment
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment
• Has known intolerance to lenvatinib, regorafenib, or TAS-102 and/or any of their excipients
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first dose of study treatment
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of Human Immunodeficiency Virus (HIV) infection
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
• Has had an allogenic tissue/solid organ transplant

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Pacific Cancer Care ( Site 0031)

Monterey, California, United States

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0021)

Marietta, Georgia, United States

University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P

Chicago, Illinois, United States

MFSMC-HJWCI-Oncology Research ( Site 0012)

Baltimore, Maryland, United States

MedStar Good Samaritan Hospital-Oncology Research ( Site 0038)

Baltimore, Maryland, United States

Henry Ford Hospital ( Site 0024)

Detroit, Michigan, United States

St. Vincent Frontier Cancer Center ( Site 0005)

Billings, Montana, United States

Providence Portland Medical Center ( Site 0019)

Portland, Oregon, United States

Thomas Jefferson University - Clinical Trials Office ( Site 0027)

Philadelphia, Pennsylvania, United States

Inova Schar Cancer Institute ( Site 0022)

Fairfax, Virginia, United States

Blue Ridge Cancer Care ( Site 0036)

Roanoke, Virginia, United States

Northwest Medical Specialties, PLLC ( Site 0033)

Tacoma, Washington, United States

Hospital Británico de Buenos Aires-Oncology ( Site 0308)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Fundación favaloro para la Docencia e Investigación Médica-Oncología ( Site 0301)

Buenos Aires, Buenos Aires F.D., Argentina

Instituto de Oncología de Rosario ( Site 0305)

Rosario, Santa Fe Province, Argentina

Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0303)

Buenos Aires, , Argentina

IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0300)

Buenos Aires, , Argentina

Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si

Brisbane, Queensland, Australia

Gallipoli Medical Research Foundation-GMRF CTU ( Site 1500)

Greenslopes, Queensland, Australia

The Queen Elizabeth Hospital-Cancer Clinical Trials ( Site 1503)

Woodville, South Australia, Australia

Epworth Freemasons ( Site 1506)

Melbourne, Victoria, Australia

Western Health-Sunshine & Footscray Hospitals ( Site 1501)

St Albans, Victoria, Australia

Hollywood Private Hospital-Medical Oncology ( Site 1507)

Perth, Western Australia, Australia

Cross Cancer Institute-Department of Medical Oncology ( Site 0207)

Edmonton, Alberta, Canada

NSHA-QEII Health Sciences Centre-Dickson Bldg-Dept. of Medical Oncology ( Site 0200)

Halifax, Nova Scotia, Canada

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0205)

Hamilton, Ontario, Canada

North York General Hospital ( Site 0206)

Toronto, Ontario, Canada

CIUSSS de l'Est-de-l'Île-de-Montréal ( Site 0211)

Montreal, Quebec, Canada

CHU de Quebec - Université Laval - Hotel Dieu de Quebec-Hemato-Dermato-Gyneco-Oncology ( Site 0203)

Québec, Quebec, Canada

The First People's Hospital of Foshan-Gastrointestinal oncology ( Site 1604)

Foshan, Guangdong, China

SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1600)

Guangzhou, Guangdong, China

Sir Run Run Shaw Hospital-Medical Oncology ( Site 1606)

Hangzhou, Zhejiang, China

Rigshospitalet ( Site 0702)

Copenhagen, Capital Region, Denmark

Herlev and Gentofte Hospital-Department of Oncology ( Site 0704)

Copenhagen, Capital Region, Denmark

Odense Universitetshospital ( Site 0700)

Odense, Region Syddanmark, Denmark

Vejle Sygehus-Department of Oncology ( Site 0701)

Vejle, Region Syddanmark, Denmark

Klinikum am Steinenberg-Kreiskliniken Reutlingen GmbH ( Site 0908)

Reutlingen, Baden-Wurttemberg, Germany

klinikum rechts der isar der technischen universität münchen-Klinik und Poliklinik für Innere Mediz

Munich, Bavaria, Germany

Onkodok GmbH ( Site 0907)

Gütersloh, North Rhine-Westphalia, Germany

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0901)

Berlin, , Germany

Asklepios Altona-Oncology ( Site 0903)

Hamburg, , Germany

Rambam Health Care Campus-Oncology ( Site 0800)

Haifa, , Israel

Shaare Zedek Medical Center-Oncology ( Site 0804)

Jerusalem, , Israel

Hadassah Medical Center-Oncology ( Site 0802)

Jerusalem, , Israel

Sheba Medical Center ( Site 0803)

Ramat Gan, , Israel

Sourasky Medical Center-Oncology ( Site 0801)

Tel Aviv, , Israel

Aichi Cancer Center Hospital ( Site 1701)

Nagoya, Aichi-ken, Japan

National Cancer Center Hospital East ( Site 1700)

Kashiwa, Chiba, Japan

Kobe City Medical Center General Hospital ( Site 1707)

Kobe, Hyōgo, Japan

Kagawa University Hospital ( Site 1708)

Kita, Kagawa-ken, Japan

Kanagawa cancer center ( Site 1705)

Yokohama, Kanagawa, Japan

Kindai University Hospital- Osakasayama Campus-Medical Oncology ( Site 1704)

Sayama, Osaka, Japan

Saitama Prefectural Cancer Center ( Site 1703)

Ina-machi, Saitama, Japan

Shizuoka Cancer Center ( Site 1706)

Nakatogari, Shizuoka, Japan

National Hospital Organization Kyushu Cancer Center ( Site 1709)

Fukuoka, , Japan

National Cancer Center Hospital ( Site 1702)

Tokyo, , Japan

Japanese Foundation for Cancer Research-GI Oncology ( Site 1710)

Tokyo, , Japan

GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1109)

Ufa, Baskortostan, Respublika, Russia

Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1100)

Saint Petersburg, Leningradskaya Oblast', Russia

The National Medico-Surgical Center N.I. Pirogov ( Site 1102)

Moscow, Moscow, Russia

Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 1107)

Moscow, Moscow, Russia

First Moscow State Medical University I.M. Sechenov-Interhospital Institution ""Health Management (

Moscow, Moscow, Russia

SVERDLOVSK REGIONAL ONCOLOGY DISPENSARY ( Site 1108)

Yekaterinburg, Sverdlovsk Oblast, Russia

SHBI Leningrad Regional Clinical Oncology Dispensary-Clinical Trials Department ( Site 1111)

Saint Petersburg, , Russia

Korea University Anam Hospital ( Site 1806)

Seoul, , South Korea

Seoul National University Hospital-Internal Medicine ( Site 1800)

Seoul, , South Korea

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1801)

Seoul, , South Korea

Asan Medical Center ( Site 1803)

Seoul, , South Korea

Samsung Medical Center-Division of Hematology/Oncology ( Site 1804)

Seoul, , South Korea

The Catholic Univ. of Korea Seoul St. Mary's Hospital ( Site 1802)

Seoul, , South Korea

Hospital Universitario Marqués de Valdecilla ( Site 1201)

Santander, Cantabria, Spain

Hospital Universitario Central de Asturias-Digestive ( Site 1200)

Oviedo, Principality of Asturias, Spain

Hospital Universitari Vall d'Hebron-Oncology ( Site 1204)

Barcelona, , Spain

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1205)

Madrid, , Spain

Hospital Universitario Virgen de Valme-Departamento de Oncologia ( Site 1207)

Seville, , Spain

China Medical University Hospital-Surgical Department ( Site 1903)

Taichung, , Taiwan

NATIONAL CHENG-KUNG UNI. HOSP. ( Site 1904)

Tainan City, , Taiwan

National Taiwan University Hospital ( Site 1900)

Taipei, , Taiwan

Taipei Veterans General Hospital-Oncology ( Site 1901)

Taipei, , Taiwan

Chang Gung Medical Foundation.Linkou Branch ( Site 1902)

Taoyuan District, , Taiwan

Hacettepe Universitesi-oncology hospital ( Site 1302)

Ankara, , Turkey (Türkiye)

Memorial Ankara Hastanesi-Medical Oncology ( Site 1304)

Ankara, , Turkey (Türkiye)

Trakya University-Oncology ( Site 1303)

Edirne, , Turkey (Türkiye)

Acıbadem Maslak Hastanesi ( Site 1307)

Istanbul, , Turkey (Türkiye)

Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1300)

Istanbul, , Turkey (Türkiye)

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1301)

Istanbul, , Turkey (Türkiye)

Ege University Medicine of Faculty-Medical Oncology ( Site 1305)

Izmir, , Turkey (Türkiye)

İnönü Üniversitesi Turgut Özal Tıp Merkezi ( Site 1306)

Malatya, , Turkey (Türkiye)

Addenbrooke's Hospital ( Site 1407)

Cambridge, Cambridgeshire, United Kingdom

UCLH-Cancer Clinical Trials Unit ( Site 1400)

London, Essex, United Kingdom

Guy's & St Thomas' NHS Foundation Trust ( Site 1404)

London, London, City of, United Kingdom

ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1403)

London, London, City of, United Kingdom

Western General Hospital ( Site 1401)

Edinburgh, Midlothian, United Kingdom

Royal Marsden Hospital (Sutton) ( Site 1409)

London, Surrey, United Kingdom

The Christie-Medical Oncology ( Site 1411)

Manchester, , United Kingdom

Countries

United States; Argentina; Australia; Canada; China; Denmark; Germany; Israel; Japan; Russia; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

Kawazoe A, Xu RH, Garcia-Alfonso P, Passhak M, Teng HW, Shergill A, Gumus M, Qvortrup C, Stintzing S, Towns K, Kim TW, Shiu KK, Cundom J, Ananda S, Lebedinets A, Fu R, Jain R, Adelberg D, Heinemann V, Yoshino T, Elez E; LEAP-017 Investigators. Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study. J Clin Oncol. 2024 Aug 20;42(24):2918-2927. doi: 10.1200/JCO.23.02736. Epub 2024 Jun 4.

Reference Type: RESULT

PMID: 38833658 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

MK-7902-017

Identifier Type: OTHER

Identifier Source: secondary_id

LEAP-017

Identifier Type: OTHER

Identifier Source: secondary_id

E7080-G000-325

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2031200453

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-004289-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

7902-017

Identifier Type: -

Identifier Source: org_study_id