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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) | Clinical Trials | Clareo Health

COMPLETEDPHASE3

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, 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)

NCT03898180•Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

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). 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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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
+15 more criteria

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.
+18 more criteria

Locations (194)

Banner MD Anderson Cancer Center ( Site 0016)

Gilbert, Arizona, United States

Community Cancer Institute ( Site 0777)

Clovis, California, United States

University of California Irvine Medical Center ( Site 0078)

Orange, California, United States

John Wayne Cancer Institute ( Site 0017)

Santa Monica, California, United States

Northwest Georgia Oncology Centers PC ( Site 0707)

Marietta, Georgia, United States

University of Chicago ( Site 0039)

Chicago, Illinois, United States

Joliet Oncology Hematology ( Site 0091)

Joliet, Illinois, United States

Quincy Medical Group ( Site 0022)

Quincy, Illinois, United States

New England Cancer Specialists ( Site 0047)

Scarborough, Maine, United States

Karmanos Cancer Institute ( Site 0712)

Detroit, Michigan, United States

Key Dates

Start Date

May 6, 2019

Primary Completion Date

July 26, 2021

Completion Date

May 20, 2024

Last Updated

February 5, 2026

Enrollment

505

ACTUAL participants

Conditions

Urothelial Carcinoma

Interventions

Pembrolizumab

BIOLOGICAL

Lenvatinib

DRUG

Placebo for lenvatinib

DRUG

Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study

NCT05987241

Muscle Invasive Bladder Urothelial CarcinomaMuscle Invasive Renal Pelvis Urothelial Carcinoma+5 more

View study

RECRUITINGPHASE2

Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial

NCT07061964

Muscle Invasive Bladder Urothelial CarcinomaStage II Bladder Cancer AJCC v8+1 more

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 5, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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)

Inclusion Criteria

Exclusion Criteria

Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study

Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial

Immune Checkpoint Inhibitor Response in Solid Tumors Using a Live Tumor Diagnostic Platform

Korean Prospective Upper Tract Urothelial Carcinoma Cohort

Low-grade UTUC Treated With Nadofaragene Firadenovec Administered to Renal Pelvis

Enfortumab Vedotin Plus Pembrolizumab With Selective Bladder Sparing for Treatment of Muscle-invasive Bladder Cancer