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)
CompletedPhase 3Results postedLast updated 5 February 2026
What this trial tests
Phase 3 trial testing Pembrolizumab in Urothelial Carcinoma in 505 participants. Completed in 20 May 2024.
18 and older, any sex, with Urothelial Carcinoma. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Progression-free Survival (PFS)Primary· Up to approximately 25 months
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
Group
Value
95% CI
Pembrolizumab + Lenvatinib
4.5
4.0 – 6.0
Pembrolizumab + Placebo
4.0
2.7 – 5.4
Overall Survival (OS)Primary· Up to approximately 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 Jul-26-2021.
Group
Value
95% CI
Pembrolizumab + Lenvatinib
11.8
9.1 – 15.1
Pembrolizumab + Placebo
12.9
9.8 – 17.8
Objective Response Rate (ORR)Secondary· Up to approximately 25 months
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.
Group
Value
95% CI
Pembrolizumab + Lenvatinib
33.1
27.2 – 39.3
Pembrolizumab + Placebo
28.9
23.3 – 35.1
Duration of Response (DOR)Secondary· Up to approximately 25 months
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 diame
Group
Value
95% CI
Pembrolizumab + Lenvatinib
NA
NA – NA
Pembrolizumab + Placebo
NA
NA – NA
Disease Control Rate (DCR)Secondary· Up to approximately 25 months
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 tum
Group
Value
95% CI
Pembrolizumab + Lenvatinib
66.9
60.7 – 72.8
Pembrolizumab + Placebo
56.2
49.7 – 62.5
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 ScoreSecondary· Baseline and Week 11
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 bett
Group
Value
95% CI
Pembrolizumab + Lenvatinib
0.73
-2.63 – 4.09
Pembrolizumab + Placebo
3.79
0.47 – 7.12
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS (Item 29) and QOL (Item 30) Combined ScoreSecondary· Baseline and up to approximately 25 months
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 sta
Group
Value
95% CI
Pembrolizumab + Lenvatinib
3.4
2.1 – 4.3
Pembrolizumab + Placebo
7.6
4.2 – NA
Number of Participants Who Experience an AESecondary· Up to approximately 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. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.
Group
Value
95% CI
Pembrolizumab + Lenvatinib
234
Pembrolizumab + Placebo
235
Number of Participants Who Discontinue Study Treatment Due to an AESecondary· Up to approximately 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. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of
Group
Value
95% CI
Pembrolizumab + Lenvatinib
83
Pembrolizumab + Placebo
44
Adverse events — posted to ClinicalTrials.gov
Time frame: Up to approximately 52 months.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Lenvatinib + Pembrolizumab First Course
Serious: 155/247 (63%)
Deaths: 178/251
Placebo + Pembrolizumab First Course
Serious: 116/254 (46%)
Deaths: 175/254
Lenvatinib + Pembrolizumab → Pembrolizumab Second Course
Serious: 0/2 (0%)
Deaths: 0/2
Placebo + Pembrolizumab → Pembrolizumab Second Course
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.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT07572123 — Evaluating the Addition of Maintenance Immunotherapy Compared to the Usual Treatment of Chemotherapy and Autologous Stem
· Phase 2, PHASE3
· not yet recruiting
NCT07275216 — Pembrolizumab in Combination With Chemotherapy for the Treatment of Frail Hodgkin Lymphoma Patients Ineligible for Stand
· Phase 2
· not yet recruiting
NCT07302347 — A Study of Pembrolizumab in Japanese Pediatric Participants With Solid Tumors or Lymphomas and Japanese Adult Participan
· Phase 1, PHASE2
· recruiting
NCT06724042 — Study of ISM5939 in Patients With Advanced and/or Metastatic Solid Tumors
· Phase 1
· not yet recruiting
NCT07383441 — Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer
· Phase 3
· not yet recruiting
Other recruiting trials for Urothelial Carcinoma
Currently open trials in the same condition.
NCT07416123 — A Study of GEN1106 in Participants With Solid Tumors
· Phase 1
· recruiting
NCT07421700 — Symbiotic-GU-06: A Study to Learn About PF-08634404 Alone or In Combination With Enfortumab Vedotin in Urothelial Cancer
· Phase 1, PHASE2
· recruiting
NCT07390617 — A Study of Neuropathy Caused by Enfortumab Vedotin in People With Urothelial Carcinoma
· recruiting
Other Merck Sharp & Dohme LLC trials
Trials by the same sponsor.
NCT07224477 — A Clinical Study of V540A in Healthy Female Participants (V540A-005)
· Phase 2
· not yet recruiting
NCT07302347 — A Study of Pembrolizumab in Japanese Pediatric Participants With Solid Tumors or Lymphomas and Japanese Adult Participan
· Phase 1, PHASE2
· recruiting
NCT07528508 — A Clinical Trial in Healthy Participants to Study the Effect of a Single Dose of MK-8527 on Levels of Methadone (MK-8527
· Phase 1
· not yet recruiting
NCT07513376 — A Clinical Trial of Adjuvant Intismeran (V940) With or Without Pembrolizumab Coformulated With Berahyaluronidase Alfa (M
· Phase 3
· not yet recruiting
NCT07532304 — A Clinical Trial of MK-4646 With Bictegravir/Emtricitabine/Tenofovir Alafenamide and Dolutegravir in Healthy Adult Parti
· Phase 1
· not yet recruiting
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Merck Sharp & Dohme LLC
Last refreshed: 5 February 2026
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03898180.