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)

  • End date
    Oct 31, 2023
  • participants needed
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 2 September 2021
Toll Free Number
Primary Contact
Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz ( Site 0506) (1.4 mi away) Contact
+229 other location
radical cystectomy
hearing loss
solid tumour
bladder cancer
invasive bladder cancer
platinum-based chemotherapy
metastatic urothelial carcinoma


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).

Condition Transitional cell carcinoma, Urothelial Carcinoma
Treatment Pembrolizumab, Lenvatinib, Placebo for lenvatinib
Clinical Study IdentifierNCT03898180
SponsorMerck Sharp & Dohme Corp.
Last Modified on2 September 2021


Yes No Not Sure

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
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
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