AzTrials
AzTrials

Urothelial CarcinomaPhase 3NCT03898180

Study of First-line Pembrolizumab (MK-3475) With Lenvatinib (MK-7902/E7080) in Urothelial Carcinoma Cisplatin-ineligible Participants Whose Tumors Express Programmed Cell Death-Ligand 1 and in Participants Ineligible for Platinum-containing Chemotherapy (MK-7902-011/E7080-G000-317/ LEAP-011)

A Phase 3 study testing Pembrolizumab and Lenvatinib in people with Urothelial Carcinoma, run by Merck Sharp & Dohme LLC at 194 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the efficacy and safety of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in the treatment of cisplatin-ineligible participants with a Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10, or in participants ineligible for any… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
Pembrolizumab and Lenvatinib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
505 participants
Where
194 sitesin 20 countries
Study dates
6 May 2019to 20 May 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial carcinoma (UC) of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
  • Has ≥1 measurable target lesion per RECIST 1.1 as assessed by the local site investigator/radiologist.
  • Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated and adequate for Programmed Death-Ligand 1 (PD-L1) evaluation.
  • Has received no prior systemic chemotherapy for advanced or metastatic UC with the following exceptions:
  • Neoadjuvant (prior to surgery) platinum-based chemotherapy for treatment of muscle-invasive bladder cancer with recurrence >12 months from completion of the therapy is permitted.
  • Adjuvant (following surgery) platinum-based chemotherapy following radical cystectomy, with recurrence >12 months from completion of the therapy, is permitted.
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  • Meets criteria for either option a or option b (below):
  • a. Has a tumor(s) with PD-L1 combined positive score (CPS) ≥10 and is considered ineligible to receive cisplatin-based combination therapy, based on 1 of the following:
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 2 within 7 days prior to randomization
  • National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade ≥2 audiometric hearing loss
  • NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy OR
  • b. In the opinion of the investigator, is considered ineligible to receive any platinum-based chemotherapy (i.e., ineligible for cisplatin and carboplatin) based on:
  • ECOG PS of 2 within 7 days prior to randomization and ≥1 of the following:
  • Documented visceral metastatic disease
  • NCI CTCAE Version 4.0 Grade ≥2 audiometric hearing loss
  • NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy
  • Other reason for the participant's being unable to receive both cisplatin and carboplatin safely. Additional criteria for platinum ineligibility will be considered and allowed on a case-by-case basis, following consultation with the Sponsor. Note: Participants considered ineligible for any platinum-based chemotherapy are eligible for this study regardless of their tumor PD-L1 status.
  • Has ECOG PS 0, 1, or 2 within 7 days prior to randomization and a life expectancy of ≥3 months.
  • Male participants are eligible to participate if they agree to the following during the treatment period and for ≥30 days after the last dose of pembrolizumab or lenvatinib/placebo:
  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR
  • Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:
  • Agrees to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding and if she is not a WOCBP OR is a WOCBP and is using a contraceptive method that is highly effective (with a failure rate of <1% per year) with low user dependency, or is abstinent from heterosexual intercourse as her preferred and usual lifestyle during the intervention period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/placebo.
  • Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg at screening and no change in antihypertensive medications within 1 week prior to randomization.
  • Has adequate organ function.

Who cannot join

  • Has disease that is suitable for local therapy administered with curative intent (e.g. chemotherapy and radiation for Stage 3 disease).
  • Has tumor with any neuroendocrine or small cell component.
  • Has a history of a gastrointestinal condition or procedure (e.g. gastric bypass, malabsorption) that, in the opinion of the investigator, may affect oral drug absorption.
  • Has had major surgery within 3 weeks prior to the first dose of study treatment
  • Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
  • Has radiographic evidence of major blood vessel invasion/infiltration, or has had clinically significant hemoptysis (≥0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks prior to the first dose of study treatment.
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  • Has had significant cardiovascular impairment within 12 months of the first dose of study treatment, such as history of New York Heart Association (NYHA) >Class II congestive heart failure, unstable angina, myocardial infarction or cerebrovascular accident (CVA)/stroke, cardiac revascularization procedure, or cardiac arrhythmia associated with hemodynamic instability.
  • Has known intolerance or severe hypersensitivity (Grade ≥3) to pembrolizumab or lenvatinib or any of their excipients
  • Has received lenvatinib as monotherapy or in combination with a programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor or has previously been enrolled in a clinical study evaluating lenvatinib for bladder cancer, regardless of the treatment received.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 inhibitor, indoleamine-pyrrole 2,3 dioxygenase (IDO1) inhibitor, or agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], OX 40, CD137), or any other antibody or drug targeting T-cell costimulatory pathways in the adjuvant or advanced/metastatic setting.
  • Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study treatment. Participants must have recovered from all radiation-related toxicities, and must not require corticosteroids.
  • Has received a live vaccine within 30 days prior to the first dose of study treatment.
  • In the investigator's judgment, has not recovered from toxicity or other complications from any major surgery prior to starting study treatment.
  • 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. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
  • Has history or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.
  • Has had an active malignancy (except locally advanced or metastatic UC) within the past 36 months. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded.
  • Has a history of prostate cancer (T2NXMX or lower with Gleason score ≤7) treated with definitive intent (surgically or with radiation therapy) ≥1 year prior to study entry is acceptable, provided that the participant is considered prostate cancer-free.
  • Has central nervous system (CNS) metastases, unless the participant has completed local therapy (e.g. whole brain radiation therapy, surgery, or radiosurgery) and has discontinued use of corticosteroids for this indication for ≥4 weeks before starting study treatment. Any signs (e.g. radiologic) or symptoms of CNS metastases must be stable for ≥4 weeks before starting study treatment.
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with disease-modifying agents, corticosteroids, or immunosuppressive drugs).
  • Has a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of or is positive for active hepatitis B virus (HBV) or has active hepatitis C virus (HCV).
  • Has active tuberculosis (TB).
  • Is receiving hemodialysis.
  • 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 pembrolizumab and lenvatinib/placebo.
  • Has had an allogeneic tissue/solid organ transplant.

Trial locations and contacts

194 sites in 20 countries.

194 sites in 20 countries

United States21 sites

  • St. Peter's Hospital Cancer Care Center ( Site 0042)

    Albany, New York, 12208

  • Medical University of South Carolina-Hollings Cancer Center ( Site 0029)

    Charleston, South Carolina, 29425

  • University of Chicago ( Site 0039)

    Chicago, Illinois, 60637

  • Community Cancer Institute ( Site 0777)

    Clovis, California, 93611

  • Karmanos Cancer Institute ( Site 0712)

    Detroit, Michigan, 48201

  • Banner MD Anderson Cancer Center ( Site 0016)

    Gilbert, Arizona, 85234

  • Joliet Oncology Hematology ( Site 0091)

    Joliet, Illinois, 60436

  • Comprehensive Cancer Centers of Nevada ( Site 0005)

    Las Vegas, Nevada, 89169

  • Northwest Georgia Oncology Centers PC ( Site 0707)

    Marietta, Georgia, 30060

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0002)

    New York, New York, 10016

  • University of California Irvine Medical Center ( Site 0078)

    Orange, California, 92868

  • Thomas Jefferson University Hospital ( Site 0051)

    Philadelphia, Pennsylvania, 19107

  • Quincy Medical Group ( Site 0022)

    Quincy, Illinois, 62301

  • Virginia Cancer Institute ( Site 0099)

    Richmond, Virginia, 23230

  • John Wayne Cancer Institute ( Site 0017)

    Santa Monica, California, 90404

  • New England Cancer Specialists ( Site 0047)

    Scarborough, Maine, 04074

  • Seattle Cancer Care Alliance ( Site 0003)

    Seattle, Washington, 98109

  • Cancer Care Northwest ( Site 0009)

    Spokane, Washington, 99218

  • Mercy Hospital Saint Louis - David C. Pratt Cancer Center ( Site 0095)

    St Louis, Missouri, 63141

  • Baylor Scott & White Medical Center - Temple ( Site 0706)

    Temple, Texas, 76508

  • Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0774)

    Tulsa, Oklahoma, 74146

Other trials in United States

China18 sites

  • Peking University First Hospital ( Site 0726)

    Beijing, Beijing Municipality, 100034

  • Fifth Medical Center of CPLA General Hospital ( Site 0732)

    Beijing, Beijing Municipality, 100071

  • Peking University Third Hospital ( Site 0727)

    Beijing, Beijing Municipality, 100089

  • Hunan Cancer Hospital ( Site 0745)

    Changsha, Hunan, 410013

  • Chongqing Cancer Hospital ( Site 0741)

    Chongging, Chongqing Municipality, 400030

  • Sun Yat-Sen University Cancer Center ( Site 0752)

    Guangdong, Guangdong, 510060

  • The First Affiliated Hospital of Guangzhou Medical University ( Site 0749)

    Guangzhou, Guangdong, 510230

  • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 0746)

    Guangzhou, Guangdong, 510289

  • Second Affiliated Hospital, Zhejiang University ( Site 0734)

    Hangzhou, Zhejiang, 310009

  • Zhejiang Provincial People's Hospital ( Site 0735)

    Hangzhou, Zhejiang, 310014

  • Harbin Medical University Cancer Hospital ( Site 0750)

    Harbin, Heilongjiang, 150081

  • Nanjing Drum Tower Hospital ( Site 0737)

    Nanjing, Jiangsu, 210008

  • Fudan University Shanghai Cancer Center ( Site 0721)

    Shanghai, Shanghai Municipality, 200032

  • Zhongshan Hospital Fudan University ( Site 0725)

    Shanghai, Shanghai Municipality, 200032

  • Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0751)

    Ürümqi, Xinjiang, 830011

  • Hubei Cancer Hospital ( Site 0744)

    Wuhan, Hubei, 430079

  • The First Affiliated Hospital of Xiamen University ( Site 0743)

    Xiamen, Fujian, 361003

  • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0738)

    Xian, Shanxi, 710061

Other trials in China

France15 sites

  • Institut de Cancerologie de l Ouest Site Paul Papin ( Site 0236)

    Angers, Maine-et-Loire, 49055

  • Centre Hospitalier de la Cote Basque ( Site 0239)

    Bayonne, Pyrenees-Atlantiques, 64109

  • CHU de Bordeaux- Hopital Saint Andre ( Site 0235)

    Bordeaux, Gironde, 33075

  • CHD Vendee-onco-hematologie ( Site 0251)

    La Roche-sur-Yon, Vendee, 85925

  • Centre Leon Berard ( Site 0244)

    Lyon, Rhone, 69373

  • Hopital de la Timone ( Site 0246)

    Marseille, Bouches-du-Rhone, 13005

  • Centre de Cancerologie du Grand Montpellier ( Site 0249)

    Montpellier, Languedoc-Roussillon, 34070

  • Centre D Oncologie de Gentilly ( Site 0240)

    Nancy, Meurthe-et-Moselle, 54100

  • Institut Curie ( Site 0237)

    Paris, 75005

  • CHU Poitiers ( Site 0253)

    Poitiers, Ain, 86021

  • CHIC Quimper ( Site 0245)

    Quimper, Finistere, 29107

  • Centre Rene Gauducheau ICO ( Site 0250)

    Saint-Herblain, Loire-Atlantique, 44805

  • Institut de Cancerologie Strasbourg Europe ( Site 0232)

    Strasbourg, Alsace, 67033

  • Clinique Pasteur ( Site 0252)

    Tolouse, Haute-Garonne, 31076

  • Institut Gustave Roussy ( Site 0243)

    Villejuif, Val-de-Marne, 94805

Other trials in France

Japan15 sites

  • Akita University Hospital ( Site 0124)

    Akita, 010-8543

  • Chiba Cancer Center ( Site 0127)

    Chiba, 260-8717

  • Saitama Medical University International Medical Center ( Site 0125)

    Hidaka, Saitama, 350-1298

  • Hirosaki University Hospital ( Site 0123)

    Hirosaki, Aomori, 036-8563

  • Nara Medical University Hospital ( Site 0133)

    Kashihara, Nara, 634-8522

  • National Cancer Center Hospital East ( Site 0128)

    Kashiwa, Chiba, 277-8577

  • Nagasaki University Hospital ( Site 0136)

    Nagasaki, 852-8501

  • Osaka City University Hospital ( Site 0132)

    Osaka, 545-8586

  • Kitasato University Hospital ( Site 0129)

    Sagamihara, Kanagawa, 252-0375

  • Sapporo Medical University Hospital ( Site 0122)

    Sapporo, Hokkaido, 060-8543

  • Tokushima University Hospital ( Site 0134)

    Tokushima, 770-8503

  • Medical Hospital, Tokyo Medical And Dental University ( Site 0130)

    Tokyo, 113-8519

  • Ehime University Hospital ( Site 0137)

    Tōon, Ehime, 791-0295

  • University of Tsukuba Hospital ( Site 0126)

    Tsukuba, Ibaraki, 305-8576

  • Yamaguchi University Hospital ( Site 0135)

    Ube, Yamaguchi, 755-8505

Other trials in Japan

United Kingdom11 sites

  • Kent and Canterbury Hospital ( Site 0390)

    Canterbury, Kent, CT1 3NG

  • Saint Bartholomew s Hospital - London ( Site 0386)

    London, London, City of, EC1A 7BE

  • University College London Hospital NHS Foundation Trust ( Site 0380)

    London, London, City of, NW1 2PG

  • Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 0378)

    London, London, City of, W6 8RF

  • Nottingham University Hospital NHS Trust ( Site 0383)

    Nottingham, NG5 1PB

  • Derriford Hospital ( Site 0388)

    Plymouth, PL6 8DH

  • Royal Preston Hospital ( Site 0379)

    Preston, Lancashire, PR2 9HT

  • Queens Hospital-Purple Zone ( Site 0377)

    Romford, Essex, RM7 0AG

  • Weston Park Hospital ( Site 0387)

    Sheffield, Derbyshire, S10 2SJ

  • Lister Hospital ( Site 0376)

    Stevenage, Hertfordshire, SG1 4AB

  • Royal Stoke University Hospital Univ. Hosps of North Midlands NHST ( Site 0392)

    Stoke-on-Trent, ST4 6QG

Other trials in United Kingdom

Israel10 sites

  • Ha Emek Medical Center ( Site 0560)

    Afula, 1834111

  • Assuta Ashdod Public ( Site 0562)

    Ashdod, 7747629

  • Rambam Medical Center ( Site 0552)

    Haifa, 3109601

  • Shaare Zedek Medical Center ( Site 0559)

    Jerusalem, 9103102

  • Hadassah Ein Kerem Medical Center ( Site 0558)

    Jerusalem, 9112001

  • Meir Medical Center ( Site 0554)

    Kfar Saba, 4428164

  • Rabin Medical Center ( Site 0553)

    Petah Tikva, 4941492

  • Sheba Medical Center ( Site 0551)

    Ramat Gan, 5265601

  • Sourasky Medical Center ( Site 0561)

    Tel Aviv, 6423906

  • Assaf Harofeh Medical Center ( Site 0556)

    Tsrifin, 70300

Other trials in Israel

Argentina9 sites

  • Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0577)

    Berazategui, Buenos Aires, B1884BBF

  • Centro de Urología CDU ( Site 0590)

    Buenos Aires, Buenos Aires F.D., C1120AAT

  • Instituto Medico Alexander Fleming ( Site 0578)

    Buenos Aires, Buenos Aires F.D., C1426ANZ

  • Instituto de Investigaciones Metabolicas ( Site 0589)

    Buenos Aires, C1012AAR

  • Centro Medico Dra De Salvo ( Site 0593)

    Buenos Aires, C1426ANZ

  • CEMAIC ( Site 0581)

    Córdoba, X5008HHW

  • Centro Oncologico de Integracion Regional. COIR ( Site 0576)

    Mendoza, M5500AYB

  • Centro Oncológico de Rosario ( Site 0584)

    Rosario, Santa Fe Province, S2000KZE

  • Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0585)

    Viedma, Río Negro Province, R8500ACE

Other trials in Argentina

Italy9 sites

  • Centro di Riferimento Oncologico CRO ( Site 0304)

    Aviano, Pordenone, 33081

  • Istituto Tumori Giovanni Paolo II ( Site 0306)

    Bari, 70124

  • Policlinico S. Orsola - Malpighi (Bologna) ( Site 0302)

    Bologna, 40138

  • Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0305)

    Catania, 95126

  • Ospedale San Raffaele-Oncologia Medica ( Site 0309)

    Milan, Lombardy, 20132

  • ASST Grande Ospedale Metropolitano Niguarda ( Site 0307)

    Milan, Lombardy, 20162

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0301)

    Milan, 20133

  • Azienda Ospedaliera Santa Maria ( Site 0303)

    Terni, 05100

  • Ospedale Borgo Roma-Oncologia ( Site 0308)

    Verona, 37134

Other trials in Italy

Russia9 sites

  • GBUZ Leningrad Regional Clinical Oncology Dispensary ( Site 0426)

    Kuzmolovskiy Settlement, Leningradskaya Oblast', 188663

  • Russian Scientific Center of Roentgenoradiology ( Site 0424)

    Moscow, Moscow, 117485

  • Central Clinical Hospital with Polyclinic ( Site 0415)

    Moscow, Moscow, 121359

  • Medical Rehabilitation Center ( Site 0411)

    Moscow, Moscow, 125367

  • Murmansk Regional Oncology Dispensary ( Site 0420)

    Murmansk, Murmansk Oblast, 183057

  • Volga District Medical Center Federal Medical and Biological Agency ( Site 0413)

    Nizhny Novgorod, Nizhny Novgorod Oblast, 603074

  • Omsk Clinical Oncology Dispensary ( Site 0418)

    Omsk, Omsk Oblast, 644013

  • Clinical Hospital Saint Luka ( Site 0421)

    Saint Petersburg, Sankt-Peterburg, 194044

  • Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0414)

    Yaroslavl, Yaroslavl Oblast, 150054

Other trials in Russia

Spain9 sites

  • Hospital Teresa Herrera - Chuac ( Site 0357)

    A Coruña, La Coruna, 15006

  • Hospital Infanta Cristina ( Site 0355)

    Badajoz, 06080

  • Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0351)

    Badalona, Barcelona, 08916

  • Hospital General Universitari Vall d Hebron ( Site 0358)

    Barcelona, 08035

  • ICO L Hospitalet ( Site 0361)

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Universitario HM Sanchinarro ( Site 0356)

    Madrid, Madrid, Comunidad de, 28050

  • Hospital La Princesa ( Site 0862)

    Madrid, 28006

  • Hospital Universitario Gregorio Maranon ( Site 0352)

    Madrid, 28009

  • Xarxa Assistencial Universitaria Manresa ( Site 0354)

    Manresa, Barcelona, 08243

Other trials in Spain

Germany8 sites

  • Universitaetsklinikum Essen ( Site 0274)

    Essen, North Rhine-Westphalia, 45147

  • Universitaetsmedizin Goettingen ( Site 0281)

    Göttingen, Lower Saxony, 37075

  • Universitaetsklinikum Hamburg-Eppendorf ( Site 0282)

    Hamburg, 20246

  • Staedtisches Krankenhaus Kiel GmbH ( Site 0285)

    Kiel, Schleswig-Holstein, 24116

  • Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0277)

    Lübeck, Schleswig-Holstein, 23538

  • Universitaetsklinikum Giessen und Marburg GmbH ( Site 0284)

    Marburg, Hesse, 35032

  • Helios Kliniken Schwerin GmbH ( Site 0278)

    Schwerin, Mecklenburg-Vorpommern, 19049

  • Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0271)

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Hungary8 sites

  • Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 0509)

    Budapest, 1106

  • Orszagos Onkologiai Intezet ( Site 0503)

    Budapest, 1122

  • Uzsoki Utcai Korhaz ( Site 0508)

    Budapest, 1145

  • Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0504)

    Kaposvár, 7400

  • Bacs-Kiskun Megyei Korhaz ( Site 0510)

    Kecskemét, Bács-Kiskun county, 6000

  • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce

    Miskolc, Borsod-Abauj Zemplen county, 3526

  • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0507)

    Szolnok, Jász-Nagykun-Szolnok, 5000

  • Markusovszky Egyetemi Oktatokorhaz ( Site 0502)

    Szombathely, Vas County, 9400

Other trials in Hungary

Netherlands8 sites

  • Ziekenhuis Rijnstate ( Site 0342)

    Arnhem, Gelderland, 6815 AD

  • Amphia Ziekenhuis Breda ( Site 0331)

    Breda, North Brabant, 4819 EV

  • Deventer Ziekenhuis ( Site 0341)

    Deventer, Overijssel, 7416 SE

  • Maastricht Universitair Medisch Centrum - MUMC ( Site 0334)

    Maastricht, Limburg, 6229 HX

  • Erasmus MC ( Site 0332)

    Rotterdam, South Holland, 3015 GD

  • Haga Ziekenhuis ( Site 0333)

    The Hague, South Holland, 2545 AA

  • St. Antonius Ziekenhuis ( Site 0335)

    Utrecht, 3543 AZ

  • VieCuri Medisch Centrum ( Site 0340)

    Venlo, Limburg, 5912 BL

Other trials in Netherlands

South Korea8 sites

  • Chungnam National University Hospital ( Site 0195)

    Daejeon, Taejon-Kwangyokshi, 35015

  • National Cancer Center ( Site 0196)

    Goyang-si, Kyonggi-do, 10408

  • Chonnam National University Hwasun Hospital ( Site 0194)

    Hwasun Gun, Jeonranamdo, 58128

  • Korea University Anam Hospital ( Site 0197)

    Seoul, 02841

  • Seoul National University Hospital ( Site 0191)

    Seoul, 03080

  • Severance Hospital ( Site 0192)

    Seoul, 03722

  • Veterans Health Service Medical Center ( Site 0198)

    Seoul, 05368

  • Samsung Medical Center ( Site 0193)

    Seoul, 06351

Other trials in South Korea

Turkey (Türkiye)8 sites

  • Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0457)

    Adana, 01330

  • Ankara Sehir Hastanesi ( Site 0455)

    Ankara, 06800

  • Antalya Memorial Hospital Department of Medical Oncology ( Site 0461)

    Antalya, 07020

  • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0454)

    Istanbul, 34098

  • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0459)

    Istanbul, 34722

  • Ege Universitesi Tulay Aktas Onkoloji Hastanesi ( Site 0462)

    Izmir, 35100

  • Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0456)

    Konya, 42080

  • Sakarya Universitesi Tip Fakultesi Arastirma Hastanesi ( Site 0460)

    Sakarya, 54290

Other trials in Turkey (Türkiye)

Taiwan7 sites

  • Kaohsiung Chang Gung Memorial Hospital ( Site 0217)

    Kaohsiung City, 83301

  • Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0216)

    Kaoshiung, Kaohsiung, 807

  • China Medical University Hospital ( Site 0213)

    Taichung, 40447

  • Taichung Veterans General Hospital ( Site 0214)

    Taichung, 40705

  • National Cheng Kung University Hospital ( Site 0215)

    Tainan, 70403

  • National Taiwan University Hospital ( Site 0211)

    Taipei, 100

  • Taipei Veterans General Hospital ( Site 0212)

    Taipei, 11217

Other trials in Taiwan

Poland6 sites

  • Szpital Miejski im. Jana Pawła II w Bielsku-Białej ( Site 0542)

    Bielsko-Biala, Silesian Voivodeship, 43-300

  • Europejskie Centrum Zdrowia Otwock ( Site 0532)

    Otwock, Masovian Voivodeship, 05-400

  • Urologica Praktyka Lekarska Adam Marcheluk ( Site 0543)

    Siedlce, Masovian Voivodeship, 08-110

  • Szpital Wojewodzki ( Site 1062)

    Tarnów, Lesser Poland Voivodeship, 33-100

  • Luxmed Onkologia sp. z o. o. ( Site 0541)

    Warsaw, Masovian Voivodeship, 01-748

  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0535)

    Wroclaw, Lower Silesian Voivodeship, 50-556

Other trials in Poland

Australia5 sites

  • Monash Health ( Site 0160)

    Clayton, Victoria, 3168

  • Peninsula Health Frankston Hospital ( Site 0153)

    Frankston, Victoria, 3199

  • Austin Health-Austin Hospital ( Site 0154)

    Heidelberg, Victoria, 3084

  • Macquarie University ( Site 0151)

    North Ryde, New South Wales, 2109

  • Mater Misericordiae Ltd ( Site 0158)

    South Brisbane, Queensland, 4101

Other trials in Australia

Canada5 sites

  • Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0101)

    Hamilton, Ontario, L8V 5C2

  • Lakeridge Health ( Site 0103)

    Oshawa, Ontario, L1G 2B9

  • CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0104)

    Québec, Quebec, G1R 2J6

  • CIUSSS de l Estrie Centre Hospitalier Universitaire de Sherbrooke ( Site 0102)

    Sherbrooke, Quebec, J1H5N4

  • Sunnybrook Research Institute ( Site 0106)

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Denmark5 sites

  • Aalborg Universitets Hospital ( Site 0684)

    Aalborg, North Denmark, 9000

  • Aarhus Universitets hospital ( Site 0683)

    Aarhus N, Central Jutland, 8200

  • Rigshospitalet ( Site 0680)

    Copenhagen, Capital Region, 2100

  • Herlev Hospital ( Site 0681)

    Herlev, Capital Region, 2730

  • Odense Universitetshospital ( Site 0682)

    Odense, Region Syddanmark, 5000

Other trials in Denmark

About this study

Official title: A Phase 3, Randomized, Double-blind Study to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Lenvatinib (E7080/MK-7902) Versus Pembrolizumab and Placebo as First Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma in Cisplatin-ineligible Participants Whose Tumors Express PD-L1, and in Participants Ineligible for Any Platinum-containing Chemotherapy Regardless of PD-L1 Expression (LEAP-011)

The purpose of this study is to evaluate the efficacy and safety of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in the treatment of cisplatin-ineligible participants with a Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10, or in participants ineligible for any platinum-containing chemotherapy regardless of CPS, with advanced/unresectable or metastatic urothelial carcinoma (UC).

The primary hypotheses for this study are that:

Read more
  1. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR), and
  2. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Overall Survival (OS).

Based on recommendation of the external Data Monitoring Committee (eDMC), Amendment 3 (effective: September [Sep]-24-2021) was implemented to unblind the study and discontinue lenvatinib and placebo treatment. The eDMC was then disbanded.

With Amendment 4 (effective: December-5-2022) second course pembrolizumab will no longer be offered. Any participant receiving second course pembrolizumab treatment prior to initiation of Amendment 4 will be able to complete treatment as planned. Study participation will end after the final administration of pembrolizumab. Participants who either complete 35 administrations of pembrolizumab or discontinue pembrolizumab will discontinue from the study following the safety follow-up visit. AEs and spontaneously reported pregnancies will be reported and followed per protocol. The overall study ends when the last participant completes the last study-related contact or visit, withdraws from the study, or is lost to follow-up.

Being tested
Pembrolizumab, Lenvatinib, Placebo for lenvatinib
Keywords
Advanced or metastatic urothelial cancer, Lenvatinib, Pembrolizumab, Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Medical subject headings
Carcinoma, Transitional Cell, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

    IV infusion

  • LenvatinibDrug

    Also called MK-7902, E7080, LENVIMA®

    oral capsule

  • Placebo for lenvatinibDrug

    oral capsule

Study groups in NCT03898180
Study groupRoleWhat they receive
Pembrolizumab + LenvatinibExperimentalParticipants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) until progressive disease or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinue lenvatinib.
Receives: Biological: Pembrolizumab; Drug: Lenvatinib
Pembrolizumab + PlaceboActive comparatorParticipants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years) PLUS placebo for lenvatinib via oral capsule QD until progressive disease or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinue placebo.
Receives: Biological: Pembrolizumab; Drug: Placebo for lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    PFS was defined as the time from randomization to the first documented PD per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR), or death due to any cause, whichever occurs 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. PFS as assessed by BICR per RECIST 1.1 is presented. Protocol-specified final analysis for this primary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

    Measured: Up to approximately 25 months

  2. Overall Survival (OS)

    OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. Protocol-specified final analysis for this primary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

    Measured: Up to approximately 25 months

Secondary outcomes (7)

  1. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants who had a confirmed CR (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 as assessed by BICR. The percentage of participants who experienced a CR or PR is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

    Measured: Up to approximately 25 months

  2. Duration of Response (DOR)

    For participants who demonstrated a confirmed CR (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 as assessed by BICR, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions as well as an absolute increase of ≥5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. The DOR as assessed by BICR per RECIST 1.1 for participants who experienced a confirmed CR or PR is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

    Measured: Up to approximately 25 months

  3. Disease Control Rate (DCR)

    DCR was defined as the percentage of participants who have a CR (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 PD [PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD]). DCR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. The DCR as assessed by BICR per RECIST 1.1 is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

    Measured: Up to approximately 25 months

  4. Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS) (Item 29) and Quality of Life (QOL) (Item 30) Combined Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding GHS ("How would you rate your overall health during the past week?") and QOL ("How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were 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 is presented. A higher score indicates a better outcome. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021, as specified in the Supplemental Statistical Analysis Plan (sSAP).

    Measured: Baseline and Week 11

  5. Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS (Item 29) and QOL (Item 30) Combined Score

    TTD was defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in GHS (EORTC QLQ-C30 Item 29) \& QOL (EORTC QLQ-C30 Item 30) combined score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding GHS ("How would you rate your overall health during the past week?") and QOL ("How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were 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. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021, as specified in the sSAP.

    Measured: Baseline and up to approximately 25 months

  6. Number of Participants Who Experience 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 could 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 experienced an AE is presented. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

    Measured: Up to approximately 25 months

  7. Number of Participants Who Discontinue 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 could 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 study treatment due to an AE is presented. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

    Measured: Up to approximately 25 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2019
  2. Study start6 May 2019
  3. Primary completion26 Jul 2021
  4. Study completion20 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
505 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03898180
Sponsor's protocol ID
7902-011
Other IDs
MK-7902-011, E7080-G000-317, LEAP-011, 194808, 2018-003752-21, 2018
Status last verified
Dec 2025
First submitted
29 Mar 2019
Last updated
5 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Matsubara N, de Wit R, Balar AV, Siefker-Radtke AO, Zolnierek J, Csoszi T, Shin SJ, Park SH, Atduev V, Gumus M, Su YL, Karaca SB, Cutuli HJ, Sendur MAN, Shen L, O'Hara K, Okpara CE, Franco S, Moreno BH, Grivas P, Loriot Y. Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Eur Urol. 2024 Mar;85(3):229-238. doi: 10.1016/j.eururo.2023.08.012. Epub 2023 Sep 29.

    PubMed 37778952

  • Taylor MH, Schmidt EV, Dutcus C, Pinheiro EM, Funahashi Y, Lubiniecki G, Rasco D. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021 Feb;17(6):637-648. doi: 10.2217/fon-2020-0937. Epub 2020 Dec 10.

    PubMed 33300372

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab and Lenvatinib in people with Urothelial Carcinoma, run by Merck Sharp & Dohme LLC at 194 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 194 sites in United States, China, France, Japan, United Kingdom and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: Up to approximately 25 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03898180, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.

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