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)

• ClinicalTrials.gov Identifier: NCT03898180
• Recruitment Status: Active, not recruiting
• First Posted: April 1, 2019
• Results First Posted: October 31, 2023
• Last Update Posted: February 6, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: Eisai Inc.
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

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. 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).

With Amendment 3 (effective: September [Sep]-24-2021) participants discontinued lenvatinib and placebo; participants who remained on treatment in the study arms received open-label pembrolizumab.

With Amendment 3 the external Data Monitoring Committee was discontinued.

With Amendment 4 (effective: December-5-2022) Second Course will no longer be offered. Any participant receiving Second Course treatment prior to initiation of Amendment 4 will be able to complete treatment as planned.

With Amendment 4 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. All participants in efficacy follow-up prior to initiation of Amendment 4 will stop efficacy assessments and be discontinued from the study. All participants in survival follow-up prior to initiation of Amendment 4 are considered to have completed the study and should have a final survival contact. 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.

Condition or disease	Intervention/treatment	Phase
Urothelial Carcinoma	Biological: Pembrolizumab; Drug: Lenvatinib; Drug: Placebo for lenvatinib	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 487 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: The study was unblinded with Amendment 3.
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 6, 2019
• Actual Primary Completion Date: July 26, 2021
• Estimated Study Completion Date: July 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pembrolizumab + Lenvatinib; 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 and participants who remain on treatment will receive open label pembrolizumab only, at the same dose and schedule (IV 200 mg on Day 1 of each 21-Day cycle for up to 35 cycles [up to ~2 years]).	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Lenvatinib; oral capsule; Other Names: MK-7902; E7080; LENVIMA®
Active Comparator: Pembrolizumab + Placebo; 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 and participants who remain on treatment will receive open label pembrolizumab only, at the same dose and schedule (IV 200 mg on Day 1 of each 21-Day cycle for up to 35 cycles [up to ~2 years]).	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Placebo for lenvatinib; oral capsule

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: Up to ~25 months ]
   PFS was defined as the time from randomization to the first documented progressive disease (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 July-26-2021.
2. Overall Survival (OS) [ Time Frame: Up to ~25 months ]
   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 July-26-2021.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Up to ~25 months ]
   ORR was defined as the percentage of participants who had 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 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 July-26-2021.
2. Duration of Response (DOR) [ Time Frame: Up to ~25 months ]
   For participants who demonstrated 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 as assessed by BICR, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (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 July-26-2021.
3. Disease Control Rate (DCR) [ Time Frame: Up to ~25 months ]
   DCR was defined at 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: ≥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 July-26-2021.
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 (Item 29) and Quality of Life (Item 30) Combined Score [ Time Frame: Baseline and Up to ~60 months ]
   The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented. A higher score indicates a better outcome.
5. Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score [ Time Frame: Up to ~60 months ]
   The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). TTD is 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. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome.
6. Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to ~25 months ]
   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. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of July-26-2021.
7. Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to ~25 months ]
   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. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of July-26-2021.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• 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
• 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.

Exclusion Criteria:

• 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.
• 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.

Contacts and Locations

Locations

United States, Arizona

Banner MD Anderson Cancer Center ( Site 0016)

Gilbert, Arizona, United States, 85234

United States, California

Community Cancer Institute ( Site 0777)

Clovis, California, United States, 93611

University of California Irvine Medical Center ( Site 0078)

Orange, California, United States, 92868

John Wayne Cancer Institute ( Site 0017)

Santa Monica, California, United States, 90404

United States, Georgia

Northwest Georgia Oncology Centers PC ( Site 0707)

Marietta, Georgia, United States, 30060

United States, Illinois

University of Chicago ( Site 0039)

Chicago, Illinois, United States, 60637

Joliet Oncology Hematology ( Site 0091)

Joliet, Illinois, United States, 60436

Quincy Medical Group ( Site 0022)

Quincy, Illinois, United States, 62301

United States, Maine

New England Cancer Specialists ( Site 0047)

Scarborough, Maine, United States, 04074

United States, Michigan

Karmanos Cancer Institute ( Site 0712)

Detroit, Michigan, United States, 48201

United States, Missouri

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

Saint Louis, Missouri, United States, 63141

United States, Nevada

Comprehensive Cancer Centers of Nevada ( Site 0005)

Las Vegas, Nevada, United States, 89169

United States, New York

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

Albany, New York, United States, 12208

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

New York, New York, United States, 10016

United States, Oklahoma

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

Tulsa, Oklahoma, United States, 74146

United States, Pennsylvania

Thomas Jefferson University Hospital ( Site 0051)

Philadelphia, Pennsylvania, United States, 19107

United States, South Carolina

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

Charleston, South Carolina, United States, 29425

United States, Texas

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

Temple, Texas, United States, 76508

United States, Virginia

Virginia Cancer Institute ( Site 0099)

Richmond, Virginia, United States, 23230

United States, Washington

Seattle Cancer Care Alliance ( Site 0003)

Seattle, Washington, United States, 98109

Cancer Care Northwest ( Site 0009)

Spokane, Washington, United States, 99218

Argentina

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

Berazategui, Buenos Aires, Argentina, B1884BBF

Centro de Urología CDU ( Site 0590)

Buenos Aires, Caba, Argentina, C1120AAT

Instituto Medico Alexander Fleming ( Site 0578)

Buenos Aires, Caba, Argentina, C1426ANZ

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0585)

Viedma, Rio Negro, Argentina, R8500ACE

Centro Oncológico de Rosario ( Site 0584)

Rosario, Santa Fe, Argentina, S2000KZE

Instituto de Investigaciones Metabolicas ( Site 0589)

Buenos Aires, Argentina, C1012AAR

Centro Medico Dra De Salvo ( Site 0593)

Buenos Aires, Argentina, C1426ANZ

CEMAIC ( Site 0581)

Cordoba, Argentina, X5008HHW

Centro Oncologico de Integracion Regional. COIR ( Site 0576)

Mendoza, Argentina, M5500AYB

Australia, New South Wales

Macquarie University ( Site 0151)

North Ryde, New South Wales, Australia, 2109

Australia, Queensland

Mater Misericordiae Ltd ( Site 0158)

South Brisbane, Queensland, Australia, 4101

Australia, Victoria

Monash Health ( Site 0160)

Clayton, Victoria, Australia, 3168

Peninsula Health Frankston Hospital ( Site 0153)

Frankston, Victoria, Australia, 3199

Austin Health-Austin Hospital ( Site 0154)

Heidelberg, Victoria, Australia, 3084

Canada, Ontario

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0101)

Hamilton, Ontario, Canada, L8V 5C2

Lakeridge Health ( Site 0103)

Oshawa, Ontario, Canada, L1G 2B9

Sunnybrook Research Institute ( Site 0106)

Toronto, Ontario, Canada, M4N 3M5

Canada, Quebec

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

Sherbrooke, Quebec, Canada, J1H5N4

Canada

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

Quebec, Canada, G1R 2J6

China, Beijing

Peking University First Hospital ( Site 0726)

Beijing, Beijing, China, 100034

Fifth Medical Center of CPLA General Hospital ( Site 0732)

Beijing, Beijing, China, 100071

Peking University Third Hospital ( Site 0727)

Beijing, Beijing, China, 100089

China, Chongqing

Chongqing Cancer Hospital ( Site 0741)

Chongging, Chongqing, China, 400030

China, Fujian

The First Affiliated Hospital of Xiamen University ( Site 0743)

Xiamen, Fujian, China, 361003

China, Guangdong

Sun Yat-Sen University Cancer Center ( Site 0752)

Guangdong, Guangdong, China, 510060

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

Guangzhou, Guangdong, China, 510230

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

Guangzhou, Guangdong, China, 510289

China, Heilongjiang

Harbin Medical University Cancer Hospital ( Site 0750)

Harbin, Heilongjiang, China, 150081

China, Hubei

Hubei Cancer Hospital ( Site 0744)

Wuhan, Hubei, China, 430079

China, Hunan

Hunan Cancer Hospital ( Site 0745)

Changsha, Hunan, China, 410013

China, Jiangsu

Nanjing Drum Tower Hospital ( Site 0737)

Nanjing, Jiangsu, China, 210008

China, Shanghai

Fudan University Shanghai Cancer Center ( Site 0721)

Shanghai, Shanghai, China, 200032

Zhongshan Hospital Fudan University ( Site 0725)

Shanghai, Shanghai, China, 200032

China, Shanxi

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

Xian, Shanxi, China, 710061

China, Xinjiang

Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0751)

Urumqi, Xinjiang, China, 830011

China, Zhejiang

Second Affiliated Hospital, Zhejiang University ( Site 0734)

Hangzhou, Zhejiang, China, 310009

Zhejiang Provincial People's Hospital ( Site 0735)

Hangzhou, Zhejiang, China, 310014

Denmark

Rigshospitalet ( Site 0680)

Copenhagen, Hovedstaden, Denmark, 2100

Herlev Hospital ( Site 0681)

Herlev, Hovedstaden, Denmark, 2730

Aarhus Universitets hospital ( Site 0683)

Aarhus N, Midtjylland, Denmark, 8200

Aalborg Universitets Hospital ( Site 0684)

Aalborg, Nordjylland, Denmark, 9000

Odense Universitetshospital ( Site 0682)

Odense, Syddanmark, Denmark, 5000

France

CHU Poitiers ( Site 0253)

Poitiers, Ain, France, 86021

Institut de Cancerologie Strasbourg Europe ( Site 0232)

Strasbourg, Alsace, France, 67033

Hopital de la Timone ( Site 0246)

Marseille, Bouches-du-Rhone, France, 13005

CHIC Quimper ( Site 0245)

Quimper, Finistere, France, 29107

CHU de Bordeaux- Hopital Saint Andre ( Site 0235)

Bordeaux, Gironde, France, 33075

Clinique Pasteur ( Site 0252)

Tolouse, Haute-Garonne, France, 31076

Centre de Cancerologie du Grand Montpellier ( Site 0249)

Montpellier, Languedoc-Roussillon, France, 34070

Centre Rene Gauducheau ICO ( Site 0250)

Saint Herblain, Loire-Atlantique, France, 44805

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

Angers, Maine-et-Loire, France, 49055

Centre D Oncologie de Gentilly ( Site 0240)

Nancy, Meurthe-et-Moselle, France, 54100

Centre Hospitalier de la Cote Basque ( Site 0239)

Bayonne, Pyrenees-Atlantiques, France, 64109

Centre Leon Berard ( Site 0244)

Lyon, Rhone, France, 69373

Institut Gustave Roussy ( Site 0243)

Villejuif, Val-de-Marne, France, 94805

CHD Vendee-onco-hematologie ( Site 0251)

La Roche sur Yon, Vendee, France, 85925

Institut Curie ( Site 0237)

Paris, France, 75005

Germany

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

Tuebingen, Baden-Wurttemberg, Germany, 72076

Universitaetsklinikum Giessen und Marburg GmbH ( Site 0284)

Marburg, Hessen, Germany, 35032

Helios Kliniken Schwerin GmbH ( Site 0278)

Schwerin, Mecklenburg-Vorpommern, Germany, 19049

Universitaetsmedizin Goettingen ( Site 0281)

Gottingen, Niedersachsen, Germany, 37075

Universitaetsklinikum Essen ( Site 0274)

Essen, Nordrhein-Westfalen, Germany, 45147

Staedtisches Krankenhaus Kiel GmbH ( Site 0285)

Kiel, Schleswig-Holstein, Germany, 24116

Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0277)

Luebeck, Schleswig-Holstein, Germany, 23538

Universitaetsklinikum Hamburg-Eppendorf ( Site 0282)

Hamburg, Germany, 20246

Hungary

Bacs-Kiskun Megyei Korhaz ( Site 0510)

Kecskemet, Bacs-Kiskun, Hungary, 6000

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

Miskolc, Borsod-Abauj-Zemplen, Hungary, 3526

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

Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000

Markusovszky Egyetemi Oktatokorhaz ( Site 0502)

Szombathely, Vas, Hungary, 9400

Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 0509)

Budapest, Hungary, 1106

Orszagos Onkologiai Intezet ( Site 0503)

Budapest, Hungary, 1122

Uzsoki Utcai Korhaz ( Site 0508)

Budapest, Hungary, 1145

Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0504)

Kaposvar, Hungary, 7400

Israel

Ha Emek Medical Center ( Site 0560)

Afula, Israel, 1834111

Assuta Ashdod Public ( Site 0562)

Ashdod, Israel, 7747629

Rambam Medical Center ( Site 0552)

Haifa, Israel, 3109601

Shaare Zedek Medical Center ( Site 0559)

Jerusalem, Israel, 9103102

Hadassah Ein Kerem Medical Center ( Site 0558)

Jerusalem, Israel, 9112001

Meir Medical Center ( Site 0554)

Kfar Saba, Israel, 4428164

Rabin Medical Center ( Site 0553)

Petach-Tikwa, Israel, 4941492

Sheba Medical Center ( Site 0551)

Ramat Gan, Israel, 5265601

Sourasky Medical Center ( Site 0561)

Tel Aviv, Israel, 6423906

Assaf Harofeh Medical Center ( Site 0556)

Zerifin, Israel, 70300

Italy

Ospedale San Raffaele-Oncologia Medica ( Site 0309)

Milano, Lombardia, Italy, 20132

ASST Grande Ospedale Metropolitano Niguarda ( Site 0307)

Milano, Lombardia, Italy, 20162

Centro di Riferimento Oncologico CRO ( Site 0304)

Aviano, Pordenone, Italy, 33081

Istituto Tumori Giovanni Paolo II ( Site 0306)

Bari, Italy, 70124

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

Bologna, Italy, 40138

Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0305)

Catania, Italy, 95126

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

Milano, Italy, 20133

Azienda Ospedaliera Santa Maria ( Site 0303)

Terni, Italy, 05100

Ospedale Borgo Roma-Oncologia ( Site 0308)

Verona, Italy, 37134

Japan

Hirosaki University Hospital ( Site 0123)

Hirosaki, Aomori, Japan, 036-8563

National Cancer Center Hospital East ( Site 0128)

Kashiwa, Chiba, Japan, 277-8577

Ehime University Hospital ( Site 0137)

Toon, Ehime, Japan, 791-0295

Sapporo Medical University Hospital ( Site 0122)

Sapporo, Hokkaido, Japan, 060-8543

University of Tsukuba Hospital ( Site 0126)

Tsukuba, Ibaraki, Japan, 305-8576

Kitasato University Hospital ( Site 0129)

Sagamihara, Kanagawa, Japan, 252-0375

Nara Medical University Hospital ( Site 0133)

Kashihara, Nara, Japan, 634-8522

Saitama Medical University International Medical Center ( Site 0125)

Hidaka, Saitama, Japan, 350-1298

Yamaguchi University Hospital ( Site 0135)

Ube, Yamaguchi, Japan, 755-8505

Akita University Hospital ( Site 0124)

Akita, Japan, 010-8543

Chiba Cancer Center ( Site 0127)

Chiba, Japan, 260-8717

Nagasaki University Hospital ( Site 0136)

Nagasaki, Japan, 852-8501

Osaka City University Hospital ( Site 0132)

Osaka, Japan, 545-8586

Tokushima University Hospital ( Site 0134)

Tokushima, Japan, 770-8503

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

Tokyo, Japan, 113-8519

Korea, Republic of

Chonnam National University Hwasun Hospital ( Site 0194)

Hwasun Gun, Jeonranamdo, Korea, Republic of, 58128

National Cancer Center ( Site 0196)

Goyang-si, Kyonggi-do, Korea, Republic of, 10408

Chungnam National University Hospital ( Site 0195)

Daejeon, Taejon-Kwangyokshi, Korea, Republic of, 35015

Korea University Anam Hospital ( Site 0197)

Seoul, Korea, Republic of, 02841

Seoul National University Hospital ( Site 0191)

Seoul, Korea, Republic of, 03080

Severance Hospital ( Site 0192)

Seoul, Korea, Republic of, 03722

Veterans Health Service Medical Center ( Site 0198)

Seoul, Korea, Republic of, 05368

Samsung Medical Center ( Site 0193)

Seoul, Korea, Republic of, 06351

Netherlands

Ziekenhuis Rijnstate ( Site 0342)

Arnhem, Gelderland, Netherlands, 6815 AD

Maastricht Universitair Medisch Centrum - MUMC ( Site 0334)

Maastricht, Limburg, Netherlands, 6229 HX

VieCuri Medisch Centrum ( Site 0340)

Venlo, Limburg, Netherlands, 5912 BL

Amphia Ziekenhuis Breda ( Site 0331)

Breda, Noord-Brabant, Netherlands, 4819 EV

Deventer Ziekenhuis ( Site 0341)

Deventer, Overijssel, Netherlands, 7416 SE

Haga Ziekenhuis ( Site 0333)

Den Haag, Zuid-Holland, Netherlands, 2545 AA

Erasmus MC ( Site 0332)

Rotterdam, Zuid-Holland, Netherlands, 3015 GD

St. Antonius Ziekenhuis ( Site 0335)

Utrecht, Netherlands, 3543 AZ

Poland

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

Wroclaw, Dolnoslaskie, Poland, 50-556

Szpital Wojewodzki ( Site 1062)

Tarnow, Malopolskie, Poland, 33-100

Europejskie Centrum Zdrowia Otwock ( Site 0532)

Otwock, Mazowieckie, Poland, 05-400

Urologica Praktyka Lekarska Adam Marcheluk ( Site 0543)

Siedlce, Mazowieckie, Poland, 08-110

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

Warszawa, Mazowieckie, Poland, 01-748

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

Bielsko-Biala, Slaskie, Poland, 43-300

Russian Federation

GBUZ Leningrad Regional Clinical Oncology Dispensary ( Site 0426)

Kuzmolovskiy Settlement, Leningradskaya Oblast, Russian Federation, 188663

Russian Scientific Center of Roentgenoradiology ( Site 0424)

Moscow, Moskva, Russian Federation, 117485

Central Clinical Hospital with Polyclinic ( Site 0415)

Moscow, Moskva, Russian Federation, 121359

Medical Rehabilitation Center ( Site 0411)

Moscow, Moskva, Russian Federation, 125367

Murmansk Regional Oncology Dispensary ( Site 0420)

Murmansk, Murmanskaya Oblast, Russian Federation, 183057

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

Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation, 603074

Omsk Clinical Oncology Dispensary ( Site 0418)

Omsk, Omskaya Oblast, Russian Federation, 644013

Clinical Hospital Saint Luka ( Site 0421)

Saint-Petersburg, Sankt-Peterburg, Russian Federation, 194044

Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0414)

Yaroslavl, Yaroslavskaya Oblast, Russian Federation, 150054

Spain

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

Badalona, Barcelona, Spain, 08916

ICO L Hospitalet ( Site 0361)

Hospitalet de Llobregat, Barcelona, Spain, 08908

Xarxa Assistencial Universitaria Manresa ( Site 0354)

Manresa, Barcelona, Spain, 08243

Hospital Teresa Herrera - Chuac ( Site 0357)

A Coruna, La Coruna, Spain, 15006

Hospital Universitario HM Sanchinarro ( Site 0356)

Madrid, Madrid, Comunidad De, Spain, 28050

Hospital Infanta Cristina ( Site 0355)

Badajoz, Spain, 06080

Hospital General Universitari Vall d Hebron ( Site 0358)

Barcelona, Spain, 08035

Hospital La Princesa ( Site 0862)

Madrid, Spain, 28006

Hospital Universitario Gregorio Maranon ( Site 0352)

Madrid, Spain, 28009

Taiwan

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

Kaoshiung, Kaohsiung, Taiwan, 807

Kaohsiung Chang Gung Memorial Hospital ( Site 0217)

Kaohsiung, Taiwan, 83301

China Medical University Hospital ( Site 0213)

Taichung, Taiwan, 40447

Taichung Veterans General Hospital ( Site 0214)

Taichung, Taiwan, 40705

National Cheng Kung University Hospital ( Site 0215)

Tainan, Taiwan, 70403

National Taiwan University Hospital ( Site 0211)

Taipei, Taiwan, 100

Taipei Veterans General Hospital ( Site 0212)

Taipei, Taiwan, 11217

Turkey

Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0457)

Adana, Turkey, 01330

Ankara Sehir Hastanesi ( Site 0455)

Ankara, Turkey, 06800

Antalya Memorial Hospital Department of Medical Oncology ( Site 0461)

Antalya, Turkey, 07020

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0454)

Istanbul, Turkey, 34098

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

Istanbul, Turkey, 34722

Ege Universitesi Tulay Aktas Onkoloji Hastanesi ( Site 0462)

İzmir, Turkey, 35100

Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0456)

Konya, Turkey, 42080

Sakarya Universitesi Tip Fakultesi Arastirma Hastanesi ( Site 0460)

Sakarya, Turkey, 54290

United Kingdom

Weston Park Hospital ( Site 0387)

Sheffield, Derbyshire, United Kingdom, S10 2SJ

Queens Hospital-Purple Zone ( Site 0377)

Romford, Essex, United Kingdom, RM7 0AG

Lister Hospital ( Site 0376)

Stevenage, Hertfordshire, United Kingdom, SG1 4AB

Kent and Canterbury Hospital ( Site 0390)

Canterbury, Kent, United Kingdom, CT1 3NG

Royal Preston Hospital ( Site 0379)

Preston, Lancashire, United Kingdom, PR2 9HT

Saint Bartholomew s Hospital - London ( Site 0386)

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

University College London Hospital NHS Foundation Trust ( Site 0380)

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

Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 0378)

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

Nottingham University Hospital NHS Trust ( Site 0383)

Nottingham, United Kingdom, NG5 1PB

Derriford Hospital ( Site 0388)

Plymouth, United Kingdom, PL6 8DH

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

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

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Eisai Inc.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:

Study Protocol and Statistical Analysis Plan  [PDF] December 5, 2022

More Information

Additional Information:

Merck Clinical Trials Information 

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03898180
• Other Study ID Numbers: 7902-011; MK-7902-011 ( Other Identifier: Merck ); E7080-G000-317 ( Other Identifier: Eisai ); LEAP-011 ( Other Identifier: Merck ); 194808 ( Registry Identifier: JAPIC-CTI ); 2018-003752-21 ( EudraCT Number )
• First Posted: April 1, 2019
• Results First Posted: October 31, 2023
• Last Update Posted: February 6, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme LLC:

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)

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Transitional Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pembrolizumab; Lenvatinib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Protein Kinase Inhibitors; Enzyme Inhibitors