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)

NCT04776148 | Completed Phase 3 Results DMC FDA Drug

• 6 other identifiers: 7902-017MK-7902-017LEAP-017E7080-G000-325jRCT20312004532020-004289-20
• Study Type: interventional
• Target: 563
• Locations: 15 countries
• Sites: 95

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.

Conditions

Colorectal Neoplasms

Keywords

Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Programmed Cell Death Receptor Ligand 2 (PD-L2); PD-1; PDL1; PD-L1; PD-L2

Outcome Measures

Primary Outcomes (2)

• Global Cohort: Overall Survival (OS)

  OS was defined as the time from randomization to the date of death from any cause. Per the supplemental Statistical Analysis Plan (sSAP), Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.

  Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

• China Cohort: Overall Survival (OS)

  OS was defined as the time from randomization to the date of death from any cause. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.

  Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

Secondary Outcomes (18)

• Global Cohort: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

  Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

• China Cohort: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

  Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

• Global Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

  Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

• China Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

  Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

• Global Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

  Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

Study Arms (2)

lenvatinib+pembrolizumab

EXPERIMENTAL

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.

Drug: pembrolizumab; Drug: lenvatinib

standard of care treatment (regorafenib OR TAS-102)

ACTIVE COMPARATOR

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.

Drug: regorafenib; Drug: TAS-102 (trifluridine and tipiracil)

Interventions

lenvatinib DRUG

oral capsule

Also known as: MK-7902, E7080

lenvatinib+pembrolizumab

regorafenib DRUG

oral tablet

Also known as: STIVARGA®, REGONIX®

standard of care treatment (regorafenib OR TAS-102)

pembrolizumab DRUG

IV infusion

Also known as: KEYTRUDA®, MK-3475

lenvatinib+pembrolizumab

TAS-102 (trifluridine and tipiracil) DRUG

oral tablet

Also known as: LONSURF®

standard of care treatment (regorafenib OR TAS-102)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• fluoropyrimidine, irinotecan and oxaliplatin
• with or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (bevacizumab)
• with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for RAS (KRAS/NRAS) wild-type (WT) participants
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Eisai Inc.: collaborator

Study Sites (95)

Pacific Cancer Care ( Site 0031)

Monterey, California, 93940, United States

Location

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

Marietta, Georgia, 30060, United States

Location

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

Chicago, Illinois, 60637, United States

Location

MFSMC-HJWCI-Oncology Research ( Site 0012)

Baltimore, Maryland, 21237, United States

Location

MedStar Good Samaritan Hospital-Oncology Research ( Site 0038)

Baltimore, Maryland, 21239, United States

Location

Henry Ford Hospital ( Site 0024)

Detroit, Michigan, 48202, United States

Location

St. Vincent Frontier Cancer Center ( Site 0005)

Billings, Montana, 59102, United States

Location

Providence Portland Medical Center ( Site 0019)

Portland, Oregon, 97213, United States

Location

Thomas Jefferson University - Clinical Trials Office ( Site 0027)

Philadelphia, Pennsylvania, 19107, United States

Location

Inova Schar Cancer Institute ( Site 0022)

Fairfax, Virginia, 22031, United States

Location

Blue Ridge Cancer Care ( Site 0036)

Roanoke, Virginia, 24014, United States

Location

Northwest Medical Specialties, PLLC ( Site 0033)

Tacoma, Washington, 98405, United States

Location

Hospital Británico de Buenos Aires-Oncology ( Site 0308)

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1280AEB, Argentina

Location

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

Buenos Aires, Buenos Aires F.D., C1096AAS, Argentina

Location

Instituto de Oncología de Rosario ( Site 0305)

Rosario, Santa Fe Province, S2000KZE, Argentina

Location

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

Buenos Aires, 1431, Argentina

Location

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

Buenos Aires, C1012AAR, Argentina

Location

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

Brisbane, Queensland, 4029, Australia

Location

Gallipoli Medical Research Foundation-GMRF CTU ( Site 1500)

Greenslopes, Queensland, 4120, Australia

Location

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

Woodville, South Australia, 5011, Australia

Location

Epworth Freemasons ( Site 1506)

Melbourne, Victoria, 3002, Australia

Location

Western Health-Sunshine & Footscray Hospitals ( Site 1501)

St Albans, Victoria, 3021, Australia

Location

Hollywood Private Hospital-Medical Oncology ( Site 1507)

Perth, Western Australia, 6009, Australia

Location

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

Edmonton, Alberta, T6G 1Z2, Canada

Location

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

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0205)

Hamilton, Ontario, L8V 4X2, Canada

Location

North York General Hospital ( Site 0206)

Toronto, Ontario, M2K1E1, Canada

Location

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

Montreal, Quebec, H1T 2M4, Canada

Location

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

Québec, Quebec, G1R 3S1, Canada

Location

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

Foshan, Guangdong, 528041, China

Location

SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1600)

Guangzhou, Guangdong, 510060, China

Location

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

Hangzhou, Zhejiang, 310016, China

Location

Rigshospitalet ( Site 0702)

Copenhagen, Capital Region, 2100, Denmark

Location

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

Copenhagen, Capital Region, 2730, Denmark

Location

Odense Universitetshospital ( Site 0700)

Odense, Region Syddanmark, 5000, Denmark

Location

Vejle Sygehus-Department of Oncology ( Site 0701)

Vejle, Region Syddanmark, DK-7100, Denmark

Location

Klinikum am Steinenberg-Kreiskliniken Reutlingen GmbH ( Site 0908)

Reutlingen, Baden-Wurttemberg, 72764, Germany

Location

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

Munich, Bavaria, 81675, Germany

Location

Onkodok GmbH ( Site 0907)

Gütersloh, North Rhine-Westphalia, 33332, Germany

Location

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0901)

Berlin, 10117, Germany

Location

Asklepios Altona-Oncology ( Site 0903)

Hamburg, 22763, Germany

Location

Rambam Health Care Campus-Oncology ( Site 0800)

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center-Oncology ( Site 0804)

Jerusalem, 9013102, Israel

Location

Hadassah Medical Center-Oncology ( Site 0802)

Jerusalem, 9112001, Israel

Location

Sheba Medical Center ( Site 0803)

Ramat Gan, 5262100, Israel

Location

Sourasky Medical Center-Oncology ( Site 0801)

Tel Aviv, 6423906, Israel

Location

Aichi Cancer Center Hospital ( Site 1701)

Nagoya, Aichi-ken, 4648681, Japan

Location

National Cancer Center Hospital East ( Site 1700)

Kashiwa, Chiba, 277-8577, Japan

Location

Kobe City Medical Center General Hospital ( Site 1707)

Kobe, Hyōgo, 650-0047, Japan

Location

Kagawa University Hospital ( Site 1708)

Kita, Kagawa-ken, 761-0701, Japan

Location

Kanagawa cancer center ( Site 1705)

Yokohama, Kanagawa, 2418515, Japan

Location

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

Sayama, Osaka, 589-8511, Japan

Location

Saitama Prefectural Cancer Center ( Site 1703)

Ina-machi, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center ( Site 1706)

Nakatogari, Shizuoka, 411-8777, Japan

Location

National Hospital Organization Kyushu Cancer Center ( Site 1709)

Fukuoka, 811-1395, Japan

Location

National Cancer Center Hospital ( Site 1702)

Tokyo, 104-0045, Japan

Location

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

Tokyo, 135-8550, Japan

Location

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

Ufa, Baskortostan, Respublika, 450054, Russia

Location

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

Saint Petersburg, Leningradskaya Oblast', 198255, Russia

Location

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

Moscow, Moscow, 105203, Russia

Location

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

Moscow, Moscow, 115478, Russia

Location

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

Moscow, Moscow, 119991, Russia

Location

SVERDLOVSK REGIONAL ONCOLOGY DISPENSARY ( Site 1108)

Yekaterinburg, Sverdlovsk Oblast, 620905, Russia

Location

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

Saint Petersburg, 188663, Russia

Location

Korea University Anam Hospital ( Site 1806)

Seoul, 02841, South Korea

Location

Seoul National University Hospital-Internal Medicine ( Site 1800)

Seoul, 03080, South Korea

Location

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

Seoul, 03722, South Korea

Location

Asan Medical Center ( Site 1803)

Seoul, 05505, South Korea

Location

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

Seoul, 06351, South Korea

Location

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

Seoul, 06591, South Korea

Location

Hospital Universitario Marqués de Valdecilla ( Site 1201)

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Central de Asturias-Digestive ( Site 1200)

Oviedo, Principality of Asturias, 33011, Spain

Location

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

Barcelona, 08035, Spain

Location

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1205)

Madrid, 28007, Spain

Location

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

Seville, 41014, Spain

Location

China Medical University Hospital-Surgical Department ( Site 1903)

Taichung, 40447, Taiwan

Location

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

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 1900)

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital-Oncology ( Site 1901)

Taipei, 11217, Taiwan

Location

Chang Gung Medical Foundation.Linkou Branch ( Site 1902)

Taoyuan District, 333, Taiwan

Location

Hacettepe Universitesi-oncology hospital ( Site 1302)

Ankara, 06230, Turkey (Türkiye)

Location

Memorial Ankara Hastanesi-Medical Oncology ( Site 1304)

Ankara, 06520, Turkey (Türkiye)

Location

Trakya University-Oncology ( Site 1303)

Edirne, 22030, Turkey (Türkiye)

Location

Acıbadem Maslak Hastanesi ( Site 1307)

Istanbul, 34457, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1300)

Istanbul, 34668, Turkey (Türkiye)

Location

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

Istanbul, 34722, Turkey (Türkiye)

Location

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

Izmir, 35100, Turkey (Türkiye)

Location

İnönü Üniversitesi Turgut Özal Tıp Merkezi ( Site 1306)

Malatya, 44280, Turkey (Türkiye)

Location

Addenbrooke's Hospital ( Site 1407)

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

UCLH-Cancer Clinical Trials Unit ( Site 1400)

London, Essex, NW1 2PG, United Kingdom

Location

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

London, London, City of, SE1 9RT, United Kingdom

Location

ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1403)

London, London, City of, SW3 6JJ, United Kingdom

Location

Western General Hospital ( Site 1401)

Edinburgh, Midlothian, EH4 2XU, United Kingdom

Location

Royal Marsden Hospital (Sutton) ( Site 1409)

London, Surrey, SM3 5PT, United Kingdom

Location

The Christie-Medical Oncology ( Site 1411)

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38833658 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Colorectal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib; regorafenib; trifluridine tipiracil drug combination; Trifluridine; tipiracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 1, 2021
• Study Start: March 29, 2021
• Primary Completion: September 27, 2024
• Study Completion: September 27, 2024
• Last Updated: February 5, 2026
• Results First Posted: April 9, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

IL (5); DE (5); CN (3); DK (4); RU (7); CA (6); AU (6); AR (5); TU (8); JP (11); US (12); ES (5); GB (7); KR (6); TW (5)