Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) in Previously Treated Participants With Select Solid Tumors (MK-7902-005/E7080-G000-224/LEAP-005)

A Multicenter, Open-label Phase 2 Study of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) in Previously Treated Subjects With Selected Solid Tumors (LEAP-005)

The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in participants with triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), biliary tract cancers (BTC), or pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Glioblastoma; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Ovarian Cancer; Advanced Solid Tumors; Triple Negative Breast Cancer; Biliary Tract Cancers
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Lenvatinib

• Study Type: Interventional
• Enrollment (Actual): 611
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1431FWO
    • CEMIC ( Site 2104)
  • Caba, Argentina, C1012AAR
    • IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 2101)
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1078AAI
      • Fundacion Favaloro para la Docencia e Investigacion Medica ( Site 2106)
  • Buenos Aires F.D.
    • Buenos Aires, Buenos Aires F.D., Argentina, 1118
      • Hospital Aleman ( Site 2100)
    • Ciudad de Buenos Aires, Buenos Aires F.D., Argentina, C1280AEB
      • Hospital Britanico de Buenos Aires ( Site 2109)
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000KZE
      • Instituto de Oncologia de Rosario ( Site 2105)
• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women s Hospital ( Site 0901)
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health ( Site 0902)
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital ( Site 0903)
• Canada
  • British Columbia
    • Abbotsford British Columbia, British Columbia, Canada, V2S 0C2
      • BC Cancer - Abbotsford ( Site 0200)
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba ( Site 0201)
  • Ontario
    • Hamilton, Ontario, Canada, L8V 4X2
      • Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0208)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute ( Site 0207)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0202)
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0210)
    • Québec, Quebec, Canada, G1R 2J6
      • CHU de Quebec Universite de Laval ( Site 0206)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4780000
      • Centro Investigación del Cáncer James Lind ( Site 1203)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7500921
      • Fundacion Arturo Lopez Perez ( Site 1201)
    • Santiago, Region M. de Santiago, Chile, 8330024
      • Pontificia Universidad Catolica de Chile ( Site 1202)
    • Santiago, Region M. de Santiago, Chile, 8380456
      • Hospital Clinico Universidad de Chile ( Site 1200)
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050030
      • Fundacion Colombiana de Cancerologia Clinica Vida ( Site 1105)
  • Bogota D.C.
    • Bogotá, Bogota D.C., Colombia, 110321
      • Instituto Nacional de Cancerologia E.S.E ( Site 1102)
  • Risaralda Department
    • Pereira, Risaralda Department, Colombia, 660001
      • Oncologos del Occidente S.A. ( Site 1106)
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760032
      • Fundacion Valle del Lili ( Site 1101)
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06189
      • Centre Antoine Lacassagne ( Site 0404)
  • Auvergne
    • Lyon, Auvergne, France, 69373
      • Centre Leon Berard ( Site 0405)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Institut Claudius Regaud IUCT Oncopole ( Site 0403)
  • Nord
    • Lille, Nord, France, 59000
      • Centre Oscar Lambret ( Site 0401)
  • Val-de-Marne
    • Saint-Herblain, Val-de-Marne, France, 44805
      • Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0402)
    • Villejuif, Val-de-Marne, France, 94800
      • Institut Gustave Roussy ( Site 0400)
• Germany
  • Baden-Wurttemberg
    • Stuttgart, Baden-Wurttemberg, Germany, 70376
      • Robert Bosch GmbH ( Site 0307)
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Universitaetsklinikum Regensburg ( Site 0304)
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60528
      • Universitaetsklinikum Frankfurt ( Site 0306)
    • Wiesbaden, Hesse, Germany, 65199
      • HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 0301)
  • Thuringia
    • Gera, Thuringia, Germany, 07548
      • SRH Wald-Klinikum Gera GmbH ( Site 0309)
    • Jena, Thuringia, Germany, 07740
      • Universitaetsklinikum Jena ( Site 0302)
• Israel
  • Beersheba, Israel, 8457108
    • Soroka Medical Center ( Site 0601)
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 0602)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Kerem Medical Center ( Site 0604)
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center ( Site 0600)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 0603)
• Italy
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori Fondazione Pascale ( Site 1400)
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A. Gemelli ( Site 1403)
  • Milano
    • Rozzano, Milano, Italy
      • Istituto Clinico Humanitas Research Hospital ( Site 1402)
  • Tuscany
    • Siena, Tuscany, Italy, 53100
      • Policlinico Le Scotte - A.O. Senese ( Site 1401)
• Russia
  • Arkhangelskaya oblast
    • Arkhangelsk, Arkhangelskaya oblast, Russia, 163045
      • Arkhangelsk Clinical Oncological Dispensary ( Site 1600)
  • Moscow
    • Moscow, Moscow, Russia, 115478
      • Russian Oncological Research Center n.a. N.N. Blokhin ( Site 1604)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 188663
      • Leningrad Regional Oncology Center ( Site 1609)
    • Saint Petersburg, Sankt-Peterburg, Russia, 197758
      • Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1610)
    • Saint Petersburg, Sankt-Peterburg, Russia, 198255
      • City Clinical Oncology Center ( Site 1608)
  • Tatarstan, Respublika
    • Kazan', Tatarstan, Respublika, Russia, 420029
      • Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1603)
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital ( Site 1000)
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System ( Site 1001)
  • Seoul
    • Songpagu, Seoul, South Korea, 05505
      • Asan Medical Center ( Site 1002)
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial ( Site 0703)
  • Madrid, Spain, 28009
    • Hospital Universitario Gregorio Maranon ( Site 0701)
  • Madrid, Spain, 28027
    • Clinica Universitaria de Navarra ( Site 0704)
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal ( Site 0702)
• Switzerland
  • Geneva, Switzerland, 1211
    • Hopitaux Universitaires de Geneve HUG ( Site 1701)
  • Zurich, Switzerland, 8091
    • Universitaetsspital Zurich ( Site 1700)
  • Canton Ticino
    • Bellinzona, Canton Ticino, Switzerland, 6500
      • Ospedale Regionale di Bellinzona e Valli ( Site 1703)
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3010
      • Inselspital Universitaetsspital Bern ( Site 1705)
  • Canton of St. Gallen
    • Sankt Gallen, Canton of St. Gallen, Switzerland, 9007
      • Kantonsspital St. Gallen ( Site 1702)
  • Kanton Graubünden
    • Chur, Kanton Graubünden, Switzerland, 7000
      • Kantonsspital Graubuenden ( Site 1704)
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 3003)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 3000)
• Thailand
  • Bangkok
    • Bangkok, Bangkok, Thailand, 10330
      • Chulalongkorn University ( Site 5001)
    • Bangkok, Bangkok, Thailand, 10400
      • Ramathibodi Hospital. ( Site 5002)
    • Bangkok, Bangkok, Thailand, 10700
      • Siriraj Hospital ( Site 5003)
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Christie NHS Foundation Trust ( Site 0805)
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Cambridge University Hospitals NHS Trust ( Site 0803)
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary. Univ. Hosp. of Leicester NHS Trust ( Site 0804)
  • London, City of
    • London, London, City of, United Kingdom, SE1 9RT
      • Guy's Hospital ( Site 0806)
  • Surrey
    • London, Surrey, United Kingdom, SM3 5PT
      • Royal Marsden Hospital (Sutton) ( Site 0800)
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope ( Site 0002)
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center ( Site 0003)
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center ( Site 0005)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Anschutz Cancer Pavilion ( Site 0007)
  • Florida
    • Orlando, Florida, United States, 32806
      • University of Florida-Health Cancer Center-Orlando ( Site 0015)
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey ( Site 0009)
  • New York
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0023)
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Sanford Fargo Medical Center ( Site 0059)
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital- Cedar Crest ( Site 0047)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center ( Site 0058)
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center - East Campus ( Site 0018)
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Centers - Medical City Hospital ( Site 0049)
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center ( Site 0021)
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-0001
      • University of Wisconsin Carbone Cancer Center ( Site 0017)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard systemic therapy has failed in one of the following cohorts: TNBC, Ovarian Cancer, Gastric Cancer, Colorectal Cancer, GBM, BTC (intrahepatic, extrahepatic cholangiocarcinoma and gall bladder cancer; excludes Ampulla of Vater), Pancreatic Cancer
• Must have progressed on or since the last treatment
• Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the local site investigator/radiology and confirmed by BICR
• Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib, or refrain from heterosexual intercourse during this period
• Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of study treatment initiation
• Has adequate organ function

For Triple Negative Breast Cancer Participants:

• Has received one or 2 prior lines of therapy
• Has Lactate Dehydrogenase (LDH) <2.0 x Upper Limit of Normal (ULN)
• Has locally determined results for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 tumor analyses

For Ovarian Cancer Participants:

- Has primary ovarian cancer and has received 3 prior lines of therapy.

For Gastric Cancer Participants:

- Has received 2 prior lines of therapy. Note: Gastric cancer will include participants with both gastric and gastroesophageal junction (GEJ) adenocarcinoma. Participants with squamous cell carcinoma histology are not eligible

For Colorectal Cancer Participants:

- Has received 2 prior lines of therapy

For GBM Participants:

• Has failed initial systemic therapy for newly diagnosed GBM
• Have the following time periods elapsed before the projected start of scheduled study treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent, 5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies and 1 week for cancer vaccines
• Be neurologically stable (e.g. without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable
• Has histologically confirmed World Health Organization (WHO) Grade IV GBM
• Has locally determined result for O^6-methylguanine-DNA methyltransferase (MGMT) analysis

For Biliary Tract Cancer Participants:

• Has received 1 prior line of therapy
• Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6

For Pancreatic Cancer Participants:

• Has pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma that is metastatic at enrollment
• Has received one or 2 prior lines of therapy
• Has received prior therapy with at least 1 (platinum-containing regimen or gemcitabine-containing regimen) but no more than 2 prior systemic therapies for unresectable or metastatic pancreatic cancer

Exclusion Criteria:

• Has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
• Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment (applies to all cohorts except the ovarian cancer cohort)
• Has radiographic evidence of encasement or invasion of a major blood vessel or of intratumoral cavitation. Participants with portal vein invasion (Vp4), inferior vena cava, or cardiac involvement based on imaging in the BTC cohort are not eligible for enrollment
• Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment
• Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA), or cardiac arrhythmia associated with hemodynamic instability
• Has a history of arterial thromboembolism within 12 months of start of study treatment
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has a serious nonhealing wound, ulcer or bone fracture
• Has had major surgery within 3 weeks prior to first dose of study interventions
• Has biologic response modifiers therapy (e.g. granulocyte colony-stimulating factor) within 4 weeks before study entry
• Has preexisting ≥Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula
• Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137])
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment start
• If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Has known intolerance to lenvatinib (and/or any of the excipients)
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• 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 treatment
• Has known active CNS metastases and/or carcinomatous meningitis
• Has tumors involving the brain stem
• 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 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 known history of active tuberculosis (TB; Bacillus tuberculosis)
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
• Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell transplant requiring chronic immunosuppressant therapy necessary to prevent graft rejection)

For GBM Participants:

• Has carcinomatous meningitis
• Has recurrent tumor greater than 6 cm in maximum diameter
• Has tumor primarily localized to the brainstem or spinal cord
• Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease
• Has evidence of intratumoral or peritumoral hemorrhage on baseline magnetic resonance imaging (MRI) scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans
• Has received Optune® TTFields within 2 weeks of study intervention

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Lenvatinib (Arm 1); Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus lenvatinib 20 mg via oral capsule once a day (QD). Pembrolizumab will be administered for up to 35 cycles (up to 2 years). Lenvatinib will be administered until progressive disease or unacceptable toxicity (up to at least 2 years).	Biological: Pembrolizumab; Administered as an IV infusion on Day 1 Q3W.; Other Names: MK-3475; Keytruda®; Drug: Lenvatinib; Administered orally once a day during each 21-day cycle.; Other Names: E7080; MK-7902; LENVIMA™
Experimental: Lenvatinib Monotherapy (Arm 2); Participants receive lenvatinib 24 mg via oral capsule QD, to be administered until progressive disease or unacceptable toxicity (up to at least 2 years).	Drug: Lenvatinib; Administered orally once a day during each 21-day cycle.; Other Names: E7080; MK-7902; LENVIMA™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator Assessment	ORR was defined as the percentage of participants who had a best overall response of either Complete Response (CR): Disappearance of all target lesions or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions as assessed by RECIST 1.1. The percentage of participants who experienced a CR or PR as assessed by RECIST 1.1 by investigator assessment was presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.	Up to approximately 66 months
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR)	ORR was defined as the percentage of participants who had a best overall response of either Complete Response (CR): Disappearance of all target lesions or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions as assessed by RECIST 1.1. For participants with GBM, response was assessed according to RANO criteria whereby ORR was defined as the percentage of participants who had a best overall response of either Complete response (CR): Disappearance of all target lesions or Partial response (PR): sum of products of diameters decreased by ≥50% from baseline value. The percentage of participants who experienced a CR or PR as assessed by RECIST 1.1 or RANO by BICR was presented. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint.	Up to approximately 66 months
Number of Participants With One or More Adverse Events (AEs)	An AE was 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 with at least one or more AE is presented.	Up to approximately 66 months
Number of Participants Who Discontinued From Study Treatment Due to an AE	An AE was 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 from study treatment due to an AE is presented.	Up to approximately 62 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR) Per RECIST 1.1 by Investigator Assessment	DCR was defined per RECIST 1.1 as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]). Disease Control rate per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.	Up to approximately 66 months
Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR	DCR was defined per RECIST 1.1 as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm]). The appearance of one or more new lesions is also considered PD.]). For participants with GBM, response was assessed according to RANO criteria whereby overall response was based on both radiographic response (CR: disappearance of all target lesions, PR: sum of products of diameters [SPD] decreased by ≥ 50% from baseline value and SD: SPD <50% decreased from baseline, but <25% increased from nadir) and clinical performance status with steroid dose information. The DCR as assessed by BICR is presented.	Up to approximately 66 months
Duration of Response (DOR) Per RECIST 1.1 by Investigator Assessment	For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD. Duration of response per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.	Up to approximately 66 months
Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR	For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD. For participants with GBM, response will be assessed according to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value) and clinical performance status with steroid dose information. DOR assessments were based on blinded central imaging review with confirmation.	Up to approximately 66 months
Progression-Free Survival (PFS) Per RECIST 1.1 by Investigator Assessment	PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ or death due to any cause, whichever occurred first. Per RECIST 1.1, 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 have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The percentage of participants who experienced PFS per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.	Up to approximately 66 months
Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR	PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on RECIST 1.1 (or RANO for GBM participants), modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ or death due to any cause, whichever occurred first. Per RECIST 1.1, 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 have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. For participants with GBM, either radiological progression or clinical deterioration (not attributable to a nontumor-related cause) qualifies as PD. The percentage of participants who experienced PFS per RECIST 1.1 or RANO by BICR is presented. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint.	Up to approximately 66 months
Overall Survival (OS)	OS was defined as the time from the date of study treatment to the date of death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants is presented.	Up to approximately 66 months
Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib	Blood samples were collected at pre-specified timepoints to determine the AUCss in participants receiving Lenvatinib (Lenva) co-administered with Pembrolizumab (Pembro). AUCss was defined as a measure of drug exposure that was calculated as the product of plasma drug concentration and time after drug administration at steady state. AUCss determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Noncompartmental analysis was used to calculate AUC0ss for each participant. Mean and standard deviation of AUCss were calculated for each cohort. As specified in the protocol, pharmacokinetic analysis was not planned or conducted in Cohorts D2 and G.	Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose (up to approximately 23 days). Each cycle is 21 days.

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Gonzalez-Martin A, Chung HC, Saada-Bouzid E, Yanez E, Senellart H, Cassier PA, Basu B, Corr BR, Girda E, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Lwin Z. Lenvatinib plus pembrolizumab for patients with previously treated advanced ovarian cancer: Results from the phase 2 multicohort LEAP-005 study. Gynecol Oncol. 2024 Jul;186:182-190. doi: 10.1016/j.ygyno.2024.04.011. Epub 2024 May 7.
• Chung HC, Saada-Bouzid E, Longo F, Yanez E, Im SA, Castanon E, Desautels DN, Graham DM, Garcia-Corbacho J, Lopez J, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Korakis I. Lenvatinib plus pembrolizumab for patients with previously treated, advanced, triple-negative breast cancer: Results from the triple-negative breast cancer cohort of the phase 2 LEAP-005 Study. Cancer. 2024 Oct 1;130(19):3278-3288. doi: 10.1002/cncr.35387. Epub 2024 Jun 21.
• Rha SY, Castanon E, Gill S, Senellart H, Lopez J, Marquez-Rodas I, Victoria I, Kim TM, Lwin Z, Burger MC, Simonelli M, Cassier PA, Hendifar AE, Ascierto PA, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Villanueva L. Lenvatinib plus pembrolizumab for patients with previously treated select solid tumors: Results from the phase 2 LEAP-005 study recurrent glioblastoma cohort. Cancer. 2025 Aug 15;131(16):e70015. doi: 10.1002/cncr.70015.
• Ponz-Sarvise M, Rha SY, Gomez-Roca CA, Ortega Moran L, Gill S, Tortora G, Geva R, Saada-Bouzid E, Santoro A, Kim TW, Heudobler D, Dutcus CE, Okpara CE, Ghori R, Zhang Y, Vajdi A, Dettman EJ, Jin F, Groisberg R, Shapira-Frommer R. Lenvatinib plus Pembrolizumab for Patients with Previously Treated Advanced Gastric, Biliary Tract, or Pancreatic Cancer: Results from the Phase II LEAP-005 Study. Cancer Res Commun. 2026 Mar 1;6(3):673-686. doi: 10.1158/2767-9764.CRC-26-0018.
• Victoria Ruiz I, Uboha NV, Jamal R, Mejia FC, Ahumada M, Im SA, Gomez-Roca C, Shapira-Frommer R, Perets R, Yanez E, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Castanon E. Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study. Clin Colorectal Cancer. 2026 Jan 22:S1533-0028(26)00005-8. doi: 10.1016/j.clcc.2026.01.003. Online ahead of print.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2019
• Primary Completion (Actual): October 28, 2024
• Study Completion (Actual): October 28, 2024

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 9, 2019

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: programmed cell death 1 (PD-1, PD1); programmed cell death ligand 1 (PD-L1, PDL1); programmed cell death ligand 2 (PD-L2, PDL2); tyrosine kinase inhibitor (TKI); multiple TKI; Vascular Endothelial Growth Factor Receptor (VEFG); Fibroblast Growth Factor (FGF); Platelet-Derived Growth Factor (PDGF)
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Pancreatic Diseases; Biliary Tract Diseases; Neoplasms, Glandular and Epithelial; Colonic Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Breast Neoplasms; Skin and Connective Tissue Diseases; Stomach Neoplasms; Biliary Tract Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Glioblastoma; Triple Negative Breast Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; pembrolizumab; lenvatinib
• Other Study ID Numbers: 7902-005; MK-7902-005 (Other Identifier: MSD Protocol Number); E7080-G000-224 (Other Identifier: Eisai Protocol Number); LEAP-005 (Other Identifier: MSD); 2018-003747-37 (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