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)

NCT03898180 | Completed Phase 3 Results DMC FDA Drug

• 6 other identifiers: 7902-011MK-7902-011E7080-G000-317LEAP-0111948082018-003752-21
• Study Type: interventional
• Target: 505
• Locations: 20 countries
• Sites: 194

Brief 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 platinum-containing chemotherapy regardless of CPS, with advanced/unresectable or metastatic urothelial carcinoma (UC). The primary hypotheses for this study are that:

1. 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. 2.Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Overall Survival (OS).

Conditions

Urothelial Carcinoma

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)

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to approximately 25 months

• 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.

  Up to approximately 25 months

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  Up to approximately 25 months

• Duration of Response (DOR)

  Up to approximately 25 months

• Disease Control Rate (DCR)

  Up to approximately 25 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 (GHS) (Item 29) and Quality of Life (QOL) (Item 30) Combined Score

  Baseline and Week 11

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

  Baseline and up to approximately 25 months

Study Arms (2)

Pembrolizumab + Lenvatinib

EXPERIMENTAL

Participants 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.

Biological: Pembrolizumab; Drug: Lenvatinib

Pembrolizumab + Placebo

ACTIVE COMPARATOR

Participants 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.

Biological: Pembrolizumab; Drug: Placebo for lenvatinib

Interventions

Placebo for lenvatinib DRUG

oral capsule

Pembrolizumab + Placebo

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab + Lenvatinib; Pembrolizumab + Placebo

Lenvatinib DRUG

oral capsule

Also known as: MK-7902, E7080, LENVIMA®

Pembrolizumab + Lenvatinib

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

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

Study Sites (194)

Banner MD Anderson Cancer Center ( Site 0016)

Gilbert, Arizona, 85234, United States

Location

Community Cancer Institute ( Site 0777)

Clovis, California, 93611, United States

Location

University of California Irvine Medical Center ( Site 0078)

Orange, California, 92868, United States

Location

John Wayne Cancer Institute ( Site 0017)

Santa Monica, California, 90404, United States

Location

Northwest Georgia Oncology Centers PC ( Site 0707)

Marietta, Georgia, 30060, United States

Location

University of Chicago ( Site 0039)

Chicago, Illinois, 60637, United States

Location

Joliet Oncology Hematology ( Site 0091)

Joliet, Illinois, 60436, United States

Location

Quincy Medical Group ( Site 0022)

Quincy, Illinois, 62301, United States

Location

New England Cancer Specialists ( Site 0047)

Scarborough, Maine, 04074, United States

Location

Karmanos Cancer Institute ( Site 0712)

Detroit, Michigan, 48201, United States

Location

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

St Louis, Missouri, 63141, United States

Location

Comprehensive Cancer Centers of Nevada ( Site 0005)

Las Vegas, Nevada, 89169, United States

Location

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

Albany, New York, 12208, United States

Location

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

New York, New York, 10016, United States

Location

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

Tulsa, Oklahoma, 74146, United States

Location

Thomas Jefferson University Hospital ( Site 0051)

Philadelphia, Pennsylvania, 19107, United States

Location

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

Charleston, South Carolina, 29425, United States

Location

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

Temple, Texas, 76508, United States

Location

Virginia Cancer Institute ( Site 0099)

Richmond, Virginia, 23230, United States

Location

Seattle Cancer Care Alliance ( Site 0003)

Seattle, Washington, 98109, United States

Location

Cancer Care Northwest ( Site 0009)

Spokane, Washington, 99218, United States

Location

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

Berazategui, Buenos Aires, B1884BBF, Argentina

Location

Centro de Urología CDU ( Site 0590)

Buenos Aires, Buenos Aires F.D., C1120AAT, Argentina

Location

Instituto Medico Alexander Fleming ( Site 0578)

Buenos Aires, Buenos Aires F.D., C1426ANZ, Argentina

Location

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0585)

Viedma, Río Negro Province, R8500ACE, Argentina

Location

Centro Oncológico de Rosario ( Site 0584)

Rosario, Santa Fe Province, S2000KZE, Argentina

Location

Instituto de Investigaciones Metabolicas ( Site 0589)

Buenos Aires, C1012AAR, Argentina

Location

Centro Medico Dra De Salvo ( Site 0593)

Buenos Aires, C1426ANZ, Argentina

Location

CEMAIC ( Site 0581)

Córdoba, X5008HHW, Argentina

Location

Centro Oncologico de Integracion Regional. COIR ( Site 0576)

Mendoza, M5500AYB, Argentina

Location

Macquarie University ( Site 0151)

North Ryde, New South Wales, 2109, Australia

Location

Mater Misericordiae Ltd ( Site 0158)

South Brisbane, Queensland, 4101, Australia

Location

Monash Health ( Site 0160)

Clayton, Victoria, 3168, Australia

Location

Peninsula Health Frankston Hospital ( Site 0153)

Frankston, Victoria, 3199, Australia

Location

Austin Health-Austin Hospital ( Site 0154)

Heidelberg, Victoria, 3084, Australia

Location

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0101)

Hamilton, Ontario, L8V 5C2, Canada

Location

Lakeridge Health ( Site 0103)

Oshawa, Ontario, L1G 2B9, Canada

Location

Sunnybrook Research Institute ( Site 0106)

Toronto, Ontario, M4N 3M5, Canada

Location

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

Québec, Quebec, G1R 2J6, Canada

Location

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

Sherbrooke, Quebec, J1H5N4, Canada

Location

Peking University First Hospital ( Site 0726)

Beijing, Beijing Municipality, 100034, China

Location

Fifth Medical Center of CPLA General Hospital ( Site 0732)

Beijing, Beijing Municipality, 100071, China

Location

Peking University Third Hospital ( Site 0727)

Beijing, Beijing Municipality, 100089, China

Location

Chongqing Cancer Hospital ( Site 0741)

Chongging, Chongqing Municipality, 400030, China

Location

The First Affiliated Hospital of Xiamen University ( Site 0743)

Xiamen, Fujian, 361003, China

Location

Sun Yat-Sen University Cancer Center ( Site 0752)

Guangdong, Guangdong, 510060, China

Location

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

Guangzhou, Guangdong, 510230, China

Location

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

Guangzhou, Guangdong, 510289, China

Location

Harbin Medical University Cancer Hospital ( Site 0750)

Harbin, Heilongjiang, 150081, China

Location

Hubei Cancer Hospital ( Site 0744)

Wuhan, Hubei, 430079, China

Location

Hunan Cancer Hospital ( Site 0745)

Changsha, Hunan, 410013, China

Location

Nanjing Drum Tower Hospital ( Site 0737)

Nanjing, Jiangsu, 210008, China

Location

Fudan University Shanghai Cancer Center ( Site 0721)

Shanghai, Shanghai Municipality, 200032, China

Location

Zhongshan Hospital Fudan University ( Site 0725)

Shanghai, Shanghai Municipality, 200032, China

Location

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

Xian, Shanxi, 710061, China

Location

Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0751)

Ürümqi, Xinjiang, 830011, China

Location

Second Affiliated Hospital, Zhejiang University ( Site 0734)

Hangzhou, Zhejiang, 310009, China

Location

Zhejiang Provincial People's Hospital ( Site 0735)

Hangzhou, Zhejiang, 310014, China

Location

Rigshospitalet ( Site 0680)

Copenhagen, Capital Region, 2100, Denmark

Location

Herlev Hospital ( Site 0681)

Herlev, Capital Region, 2730, Denmark

Location

Aarhus Universitets hospital ( Site 0683)

Aarhus N, Central Jutland, 8200, Denmark

Location

Aalborg Universitets Hospital ( Site 0684)

Aalborg, North Denmark, 9000, Denmark

Location

Odense Universitetshospital ( Site 0682)

Odense, Region Syddanmark, 5000, Denmark

Location

CHU Poitiers ( Site 0253)

Poitiers, Ain, 86021, France

Location

Institut de Cancerologie Strasbourg Europe ( Site 0232)

Strasbourg, Alsace, 67033, France

Location

Hopital de la Timone ( Site 0246)

Marseille, Bouches-du-Rhone, 13005, France

Location

CHIC Quimper ( Site 0245)

Quimper, Finistere, 29107, France

Location

CHU de Bordeaux- Hopital Saint Andre ( Site 0235)

Bordeaux, Gironde, 33075, France

Location

Clinique Pasteur ( Site 0252)

Tolouse, Haute-Garonne, 31076, France

Location

Centre de Cancerologie du Grand Montpellier ( Site 0249)

Montpellier, Languedoc-Roussillon, 34070, France

Location

Centre Rene Gauducheau ICO ( Site 0250)

Saint-Herblain, Loire-Atlantique, 44805, France

Location

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

Angers, Maine-et-Loire, 49055, France

Location

Centre D Oncologie de Gentilly ( Site 0240)

Nancy, Meurthe-et-Moselle, 54100, France

Location

Centre Hospitalier de la Cote Basque ( Site 0239)

Bayonne, Pyrenees-Atlantiques, 64109, France

Location

Centre Leon Berard ( Site 0244)

Lyon, Rhone, 69373, France

Location

Institut Gustave Roussy ( Site 0243)

Villejuif, Val-de-Marne, 94805, France

Location

CHD Vendee-onco-hematologie ( Site 0251)

La Roche-sur-Yon, Vendee, 85925, France

Location

Institut Curie ( Site 0237)

Paris, 75005, France

Location

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

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH ( Site 0284)

Marburg, Hesse, 35032, Germany

Location

Universitaetsmedizin Goettingen ( Site 0281)

Göttingen, Lower Saxony, 37075, Germany

Location

Helios Kliniken Schwerin GmbH ( Site 0278)

Schwerin, Mecklenburg-Vorpommern, 19049, Germany

Location

Universitaetsklinikum Essen ( Site 0274)

Essen, North Rhine-Westphalia, 45147, Germany

Location

Staedtisches Krankenhaus Kiel GmbH ( Site 0285)

Kiel, Schleswig-Holstein, 24116, Germany

Location

Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0277)

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf ( Site 0282)

Hamburg, 20246, Germany

Location

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

Miskolc, Borsod-Abauj Zemplen county, 3526, Hungary

Location

Bacs-Kiskun Megyei Korhaz ( Site 0510)

Kecskemét, Bács-Kiskun county, 6000, Hungary

Location

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

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

Location

Markusovszky Egyetemi Oktatokorhaz ( Site 0502)

Szombathely, Vas County, 9400, Hungary

Location

Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 0509)

Budapest, 1106, Hungary

Location

Orszagos Onkologiai Intezet ( Site 0503)

Budapest, 1122, Hungary

Location

Uzsoki Utcai Korhaz ( Site 0508)

Budapest, 1145, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0504)

Kaposvár, 7400, Hungary

Location

Ha Emek Medical Center ( Site 0560)

Afula, 1834111, Israel

Location

Assuta Ashdod Public ( Site 0562)

Ashdod, 7747629, Israel

Location

Rambam Medical Center ( Site 0552)

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center ( Site 0559)

Jerusalem, 9103102, Israel

Location

Hadassah Ein Kerem Medical Center ( Site 0558)

Jerusalem, 9112001, Israel

Location

Meir Medical Center ( Site 0554)

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center ( Site 0553)

Petah Tikva, 4941492, Israel

Location

Sheba Medical Center ( Site 0551)

Ramat Gan, 5265601, Israel

Location

Sourasky Medical Center ( Site 0561)

Tel Aviv, 6423906, Israel

Location

Assaf Harofeh Medical Center ( Site 0556)

Ẕerifin, 70300, Israel

Location

Ospedale San Raffaele-Oncologia Medica ( Site 0309)

Milan, Lombardy, 20132, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda ( Site 0307)

Milan, Lombardy, 20162, Italy

Location

Centro di Riferimento Oncologico CRO ( Site 0304)

Aviano, Pordenone, 33081, Italy

Location

Istituto Tumori Giovanni Paolo II ( Site 0306)

Bari, 70124, Italy

Location

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

Bologna, 40138, Italy

Location

Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0305)

Catania, 95126, Italy

Location

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

Milan, 20133, Italy

Location

Azienda Ospedaliera Santa Maria ( Site 0303)

Terni, 05100, Italy

Location

Ospedale Borgo Roma-Oncologia ( Site 0308)

Verona, 37134, Italy

Location

Hirosaki University Hospital ( Site 0123)

Hirosaki, Aomori, 036-8563, Japan

Location

National Cancer Center Hospital East ( Site 0128)

Kashiwa, Chiba, 277-8577, Japan

Location

Ehime University Hospital ( Site 0137)

Tōon, Ehime, 791-0295, Japan

Location

Sapporo Medical University Hospital ( Site 0122)

Sapporo, Hokkaido, 060-8543, Japan

Location

University of Tsukuba Hospital ( Site 0126)

Tsukuba, Ibaraki, 305-8576, Japan

Location

Kitasato University Hospital ( Site 0129)

Sagamihara, Kanagawa, 252-0375, Japan

Location

Nara Medical University Hospital ( Site 0133)

Kashihara, Nara, 634-8522, Japan

Location

Saitama Medical University International Medical Center ( Site 0125)

Hidaka, Saitama, 350-1298, Japan

Location

Yamaguchi University Hospital ( Site 0135)

Ube, Yamaguchi, 755-8505, Japan

Location

Akita University Hospital ( Site 0124)

Akita, 010-8543, Japan

Location

Chiba Cancer Center ( Site 0127)

Chiba, 260-8717, Japan

Location

Nagasaki University Hospital ( Site 0136)

Nagasaki, 852-8501, Japan

Location

Osaka City University Hospital ( Site 0132)

Osaka, 545-8586, Japan

Location

Tokushima University Hospital ( Site 0134)

Tokushima, 770-8503, Japan

Location

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

Tokyo, 113-8519, Japan

Location

Ziekenhuis Rijnstate ( Site 0342)

Arnhem, Gelderland, 6815 AD, Netherlands

Location

Maastricht Universitair Medisch Centrum - MUMC ( Site 0334)

Maastricht, Limburg, 6229 HX, Netherlands

Location

VieCuri Medisch Centrum ( Site 0340)

Venlo, Limburg, 5912 BL, Netherlands

Location

Amphia Ziekenhuis Breda ( Site 0331)

Breda, North Brabant, 4819 EV, Netherlands

Location

Deventer Ziekenhuis ( Site 0341)

Deventer, Overijssel, 7416 SE, Netherlands

Location

Erasmus MC ( Site 0332)

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Haga Ziekenhuis ( Site 0333)

The Hague, South Holland, 2545 AA, Netherlands

Location

St. Antonius Ziekenhuis ( Site 0335)

Utrecht, 3543 AZ, Netherlands

Location

Szpital Wojewodzki ( Site 1062)

Tarnów, Lesser Poland Voivodeship, 33-100, Poland

Location

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

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

Location

Europejskie Centrum Zdrowia Otwock ( Site 0532)

Otwock, Masovian Voivodeship, 05-400, Poland

Location

Urologica Praktyka Lekarska Adam Marcheluk ( Site 0543)

Siedlce, Masovian Voivodeship, 08-110, Poland

Location

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

Warsaw, Masovian Voivodeship, 01-748, Poland

Location

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

Bielsko-Biala, Silesian Voivodeship, 43-300, Poland

Location

GBUZ Leningrad Regional Clinical Oncology Dispensary ( Site 0426)

Kuzmolovskiy Settlement, Leningradskaya Oblast', 188663, Russia

Location

Russian Scientific Center of Roentgenoradiology ( Site 0424)

Moscow, Moscow, 117485, Russia

Location

Central Clinical Hospital with Polyclinic ( Site 0415)

Moscow, Moscow, 121359, Russia

Location

Medical Rehabilitation Center ( Site 0411)

Moscow, Moscow, 125367, Russia

Location

Murmansk Regional Oncology Dispensary ( Site 0420)

Murmansk, Murmansk Oblast, 183057, Russia

Location

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

Nizhny Novgorod, Nizhny Novgorod Oblast, 603074, Russia

Location

Omsk Clinical Oncology Dispensary ( Site 0418)

Omsk, Omsk Oblast, 644013, Russia

Location

Clinical Hospital Saint Luka ( Site 0421)

Saint Petersburg, Sankt-Peterburg, 194044, Russia

Location

Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0414)

Yaroslavl, Yaroslavl Oblast, 150054, Russia

Location

Chonnam National University Hwasun Hospital ( Site 0194)

Hwasun Gun, Jeonranamdo, 58128, South Korea

Location

National Cancer Center ( Site 0196)

Goyang-si, Kyonggi-do, 10408, South Korea

Location

Chungnam National University Hospital ( Site 0195)

Daejeon, Taejon-Kwangyokshi, 35015, South Korea

Location

Korea University Anam Hospital ( Site 0197)

Seoul, 02841, South Korea

Location

Seoul National University Hospital ( Site 0191)

Seoul, 03080, South Korea

Location

Severance Hospital ( Site 0192)

Seoul, 03722, South Korea

Location

Veterans Health Service Medical Center ( Site 0198)

Seoul, 05368, South Korea

Location

Samsung Medical Center ( Site 0193)

Seoul, 06351, South Korea

Location

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

Badalona, Barcelona, 08916, Spain

Location

ICO L Hospitalet ( Site 0361)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Xarxa Assistencial Universitaria Manresa ( Site 0354)

Manresa, Barcelona, 08243, Spain

Location

Hospital Teresa Herrera - Chuac ( Site 0357)

A Coruña, La Coruna, 15006, Spain

Location

Hospital Universitario HM Sanchinarro ( Site 0356)

Madrid, Madrid, Comunidad de, 28050, Spain

Location

Hospital Infanta Cristina ( Site 0355)

Badajoz, 06080, Spain

Location

Hospital General Universitari Vall d Hebron ( Site 0358)

Barcelona, 08035, Spain

Location

Hospital La Princesa ( Site 0862)

Madrid, 28006, Spain

Location

Hospital Universitario Gregorio Maranon ( Site 0352)

Madrid, 28009, Spain

Location

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

Kaoshiung, Kaohsiung, 807, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital ( Site 0217)

Kaohsiung City, 83301, Taiwan

Location

China Medical University Hospital ( Site 0213)

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital ( Site 0214)

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital ( Site 0215)

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital ( Site 0211)

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital ( Site 0212)

Taipei, 11217, Taiwan

Location

Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0457)

Adana, 01330, Turkey (Türkiye)

Location

Ankara Sehir Hastanesi ( Site 0455)

Ankara, 06800, Turkey (Türkiye)

Location

Antalya Memorial Hospital Department of Medical Oncology ( Site 0461)

Antalya, 07020, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0454)

Istanbul, 34098, Turkey (Türkiye)

Location

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

Istanbul, 34722, Turkey (Türkiye)

Location

Ege Universitesi Tulay Aktas Onkoloji Hastanesi ( Site 0462)

Izmir, 35100, Turkey (Türkiye)

Location

Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0456)

Konya, 42080, Turkey (Türkiye)

Location

Sakarya Universitesi Tip Fakultesi Arastirma Hastanesi ( Site 0460)

Sakarya, 54290, Turkey (Türkiye)

Location

Weston Park Hospital ( Site 0387)

Sheffield, Derbyshire, S10 2SJ, United Kingdom

Location

Queens Hospital-Purple Zone ( Site 0377)

Romford, Essex, RM7 0AG, United Kingdom

Location

Lister Hospital ( Site 0376)

Stevenage, Hertfordshire, SG1 4AB, United Kingdom

Location

Kent and Canterbury Hospital ( Site 0390)

Canterbury, Kent, CT1 3NG, United Kingdom

Location

Royal Preston Hospital ( Site 0379)

Preston, Lancashire, PR2 9HT, United Kingdom

Location

Saint Bartholomew s Hospital - London ( Site 0386)

London, London, City of, EC1A 7BE, United Kingdom

Location

University College London Hospital NHS Foundation Trust ( Site 0380)

London, London, City of, NW1 2PG, United Kingdom

Location

Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 0378)

London, London, City of, W6 8RF, United Kingdom

Location

Nottingham University Hospital NHS Trust ( Site 0383)

Nottingham, NG5 1PB, United Kingdom

Location

Derriford Hospital ( Site 0388)

Plymouth, PL6 8DH, United Kingdom

Location

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

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 37778952 RESULT

• 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.

  PMID: 33300372 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

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

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study was unblinded with Amendment 3.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 1, 2019
• Study Start: May 6, 2019
• Primary Completion: July 26, 2021
• Study Completion: May 20, 2024
• Last Updated: February 5, 2026
• Results First Posted: October 31, 2023

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

TW (7); HU (8); US (21); DK (5); AU (5); CA (5); ES (9); KR (8); NL (8); TU (8); CN (18); GB (11); RU (9); AR (9); IL (10); IT (9); FR (15); DE (8); PL (6); JP (15)