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)

A Phase 3 Randomized Study of Lenvatinib in Combination With Pembrolizumab Versus Standard of Care in Participants With Metastatic Colorectal Cancer Who Have Received and Progressed On or After or Became Intolerant to Prior Treatment

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: pembrolizumab; Drug: lenvatinib; Drug: regorafenib; Drug: TAS-102 (trifluridine and tipiracil)

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1431
    • Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0303)
  • Buenos Aires, Argentina, C1012AAR
    • IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0300)
  • Buenos Aires
    • Ciudad autónoma de Buenos Aires, Buenos Aires, Argentina, C1280AEB
      • Hospital Británico de Buenos Aires-Oncology ( Site 0308)
  • Caba
    • Buenos Aires, Caba, Argentina, C1096AAS
      • Fundación favaloro para la Docencia e Investigación Médica-Oncología ( Site 0301)
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000KZE
      • Instituto de Oncología de Rosario ( Site 0305)
• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
    • Greenslopes, Queensland, Australia, 4120
      • Gallipoli Medical Research Foundation-GMRF CTU ( Site 1500)
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital-Cancer Clinical Trials ( Site 1503)
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Epworth Freemasons ( Site 1506)
    • St Albans, Victoria, Australia, 3021
      • Western Health-Sunshine & Footscray Hospitals ( Site 1501)
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Hollywood Private Hospital-Medical Oncology ( Site 1507)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute-Department of Medical Oncology ( Site 0207)
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • NSHA-QEII Health Sciences Centre-Dickson Bldg-Dept. of Medical Oncology ( Site 0200)
  • Ontario
    • Hamilton, Ontario, Canada, L8V 4X2
      • Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0205)
    • Toronto, Ontario, Canada, M2K1E1
      • North York General Hospital ( Site 0206)
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • CIUSSS de l'Est-de-l'Île-de-Montréal ( Site 0211)
    • Québec, Quebec, Canada, G1R 3S1
      • CHU de Quebec - Université Laval - Hotel Dieu de Quebec-Hemato-Dermato-Gyneco-Oncology ( Site 0203)
• China
  • Guangdong
    • Foshan, Guangdong, China, 528041
      • The First People's Hospital of Foshan-Gastrointestinal oncology ( Site 1604)
    • Guangzhou, Guangdong, China, 510060
      • SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1600)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital-Medical Oncology ( Site 1606)
• Denmark
  • Hovedstaden
    • Copenhagen, Hovedstaden, Denmark, 2100
      • Rigshospitalet ( Site 0702)
    • Copenhagen, Hovedstaden, Denmark, 2730
      • Herlev and Gentofte Hospital-Department of Oncology ( Site 0704)
  • Syddanmark
    • Odense, Syddanmark, Denmark, 5000
      • Odense Universitetshospital ( Site 0700)
    • Vejle, Syddanmark, Denmark, DK-7100
      • Vejle Sygehus-Department of Oncology ( Site 0701)
• Germany
  • Berlin, Germany, 10117
    • Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0901)
  • Hamburg, Germany, 22763
    • Asklepios Altona-Oncology ( Site 0903)
  • Baden-Wurttemberg
    • Reutlingen, Baden-Wurttemberg, Germany, 72764
      • Klinikum am Steinenberg-Kreiskliniken Reutlingen GmbH ( Site 0908)
  • Bayern
    • Munich, Bayern, Germany, 81675
      • klinikum rechts der isar der technischen universität münchen-Klinik und Poliklinik für Innere Mediz
  • Nordrhein-Westfalen
    • Gütersloh, Nordrhein-Westfalen, Germany, 33332
      • Onkodok GmbH ( Site 0907)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Oncology ( Site 0800)
  • Jerusalem, Israel, 9013102
    • Shaare Zedek Medical Center-Oncology ( Site 0804)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center-Oncology ( Site 0802)
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center ( Site 0803)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center-Oncology ( Site 0801)
• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 1709)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 1702)
  • Tokyo, Japan, 135-8550
    • Japanese Foundation for Cancer Research-GI Oncology ( Site 1710)
  • Aichi
    • Nagoya, Aichi, Japan, 4648681
      • Aichi Cancer Center Hospital ( Site 1701)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 1700)
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital ( Site 1707)
  • Kagawa
    • Kita, Kagawa, Japan, 761-0701
      • Kagawa University Hospital ( Site 1708)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2418515
      • Kanagawa cancer center ( Site 1705)
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital- Osakasayama Campus-Medical Oncology ( Site 1704)
  • Saitama
    • Ina-machi, Saitama, Japan, 362-0806
      • Saitama Prefectural Cancer Center ( Site 1703)
  • Shizuoka
    • Nagaizumi, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center ( Site 1706)
• Korea, Republic of
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital ( Site 1806)
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital-Internal Medicine ( Site 1800)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1801)
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center ( Site 1803)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center-Division of Hematology/Oncology ( Site 1804)
  • Seoul, Korea, Republic of, 06591
    • The Catholic Univ. of Korea Seoul St. Mary's Hospital ( Site 1802)
• Russian Federation
  • Sankt-Peterburg, Russian Federation, 188663
    • SHBI Leningrad Regional Clinical Oncology Dispensary-Clinical Trials Department ( Site 1111)
  • Baskortostan, Respublika
    • Ufa, Baskortostan, Respublika, Russian Federation, 450054
      • GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1109)
  • Leningradskaya Oblast
    • Saint Petersburg, Leningradskaya Oblast, Russian Federation, 198255
      • Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1100)
  • Moskva
    • Moscow, Moskva, Russian Federation, 105203
      • The National Medico-Surgical Center N.I. Pirogov ( Site 1102)
    • Moscow, Moskva, Russian Federation, 115478
      • Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 1107)
    • Moscow, Moskva, Russian Federation, 119991
      • First Moscow State Medical University I.M. Sechenov-Interhospital Institution ""Health Management (
  • Sverdlovskaya Oblast
    • Ekaterinburg, Sverdlovskaya Oblast, Russian Federation, 620905
      • SVERDLOVSK REGIONAL ONCOLOGY DISPENSARY ( Site 1108)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron-Oncology ( Site 1204)
  • Madrid, Spain, 28007
    • HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1205)
  • Sevilla, Spain, 41014
    • Hospital Universitario Virgen de Valme-Departamento de Oncologia ( Site 1207)
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias-Digestive ( Site 1200)
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla ( Site 1201)
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital-Surgical Department ( Site 1903)
  • Tainan, Taiwan, 704
    • NATIONAL CHENG-KUNG UNI. HOSP. ( Site 1904)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 1900)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital-Oncology ( Site 1901)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation.Linkou Branch ( Site 1902)
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi-oncology hospital ( Site 1302)
  • Ankara, Turkey, 06520
    • Memorial Ankara Hastanesi-Medical Oncology ( Site 1304)
  • Edirne, Turkey, 22030
    • Trakya University-Oncology ( Site 1303)
  • Istanbul, Turkey, 34668
    • Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1300)
  • Istanbul, Turkey, 34722
    • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1301)
  • Izmir, Turkey, 35100
    • Ege University Medicine of Faculty-Medical Oncology ( Site 1305)
  • Malatya, Turkey, 44280
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi ( Site 1306)
  • İstanbul, Turkey, 34457
    • Acıbadem Maslak Hastanesi ( Site 1307)
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie-Medical Oncology ( Site 1411)
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Addenbrooke's Hospital ( Site 1407)
  • Essex
    • London, Essex, United Kingdom, NW1 2PG
      • UCLH-Cancer Clinical Trials Unit ( Site 1400)
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 9RT
      • Guy's & St Thomas' NHS Foundation Trust ( Site 1404)
    • London, London, City Of, United Kingdom, SW3 6JJ
      • ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1403)
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH4 2XU
      • Western General Hospital ( Site 1401)
  • Surrey
    • London, Surrey, United Kingdom, SM3 5PT
      • Royal Marsden Hospital (Sutton) ( Site 1409)
• United States
  • California
    • Monterey, California, United States, 93940
      • Pacific Cancer Care ( Site 0031)
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0021)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MFSMC-HJWCI-Oncology Research ( Site 0012)
    • Baltimore, Maryland, United States, 21239
      • MedStar Good Samaritan Hospital-Oncology Research ( Site 0038)
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital ( Site 0024)
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center ( Site 0005)
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center ( Site 0019)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University - Clinical Trials Office ( Site 0027)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute ( Site 0022)
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Care ( Site 0036)
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC ( Site 0033)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: lenvatinib; oral capsule; Other Names: E7080; MK-7902
Active Comparator: 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.	Drug: regorafenib; oral tablet; Other Names: STIVARGA®; REGONIX®; Drug: TAS-102 (trifluridine and tipiracil); oral tablet; Other Names: LONSURF®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to the date of death from any cause.	Up to approximately 22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per modified RECIST 1.1 is presented.	Up to approximately 22 months
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR per modified RECIST 1.1 assessed by BICR is presented.	Up to approximately 22 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR per modified RECIST 1.1 is presented.	Up to approximately 22 months
Number of Participants Who Experience an Adverse Event (AE)	An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 22 months
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued any study treatment due to an adverse event is presented.	Up to approximately 22 months
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented. A higher score indicates a better outcome.	Baseline and 8 weeks
Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function.	Baseline and 8 weeks
Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for appetite loss (QLQ-C30 Item 13). For this item, individual responses to the question "Have you lacked appetite?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 appetite loss (Item 13) scale score is presented.	Baseline and 8 weeks
Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score	The EORTC QLQ-CR29 is a health-related quality-of life (QoL) questionnaire specific for colorectal cancer, including a single-item scale score for bloating (QLQ-CR29 Item 37). For this item, individual responses to the question "Did you have a bloated feeling in your abdomen?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-CR29 bloating (Item 37) scale score is presented.	Baseline and 8 weeks
Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score	TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) & Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, is presented. A longer TTD indicates a better outcome.	Up to approximately 21 months
TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in physical functioning score, is presented. A longer TTD indicates a better outcome.	Up to approximately 21 months
TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score	TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (increase) from baseline in appetite loss (QLQ-C30 Item 13) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point change (increase) from baseline in appetite loss score, is presented. A longer TTD indicates a better outcome.	Up to approximately 21 months
TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score	TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (increase) from baseline in bloating (QLQ-CR29 Item 37) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point change (increase) from baseline in appetite loss score, is presented. A longer TTD indicates a better outcome.	Up to approximately 21 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Eisai Inc.
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2021
• Primary Completion (Actual): February 20, 2023
• Study Completion (Estimated): September 6, 2024

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: February 26, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: PD-1; PD-L1; PDL1; Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Programmed Cell Death Receptor Ligand 2 (PD-L2); PD-L2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Pembrolizumab; Lenvatinib; Trifluridine
• Other Study ID Numbers: 7902-017; MK-7902-017 (Other Identifier: Merck); LEAP-017 (Other Identifier: Merck); E7080-G000-325 (Other Identifier: Eisai); jRCT2031200453 (Registry Identifier: jRCT); 2020-004289-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No