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Clinical Trials List

Protocol NumberMK-7902-011 (E7080-G000-317)
NCT Number(ClinicalTrials.gov Identfier)NCT03898180

2019-06-01 - 2024-07-31

Phase III

Recruiting7

ICD-10C68.9

Malignant neoplasm of urinary organ, unspecified

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)

  • Trial Applicant

    Merck Sharp & Dohme (I.A.) LLC

  • Sponsor

    Merck Sharp & Dohme Corp.

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator Hsiao-Jen Chung Division of Urology
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chao-Hsiang Chang Division of Urology
China Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Shian-Shiang Wang Division of Urology
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Wen-Pin Su Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Yu-Li Su Division of Hematology & Oncology
Kaoshiung Chang Gung Memorial Hospital of the C.G.M.F.

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Yu-Chieh Tsai Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Wen-Jeng Wu Division of Urology
Kaohsiung Medical Univeristy Chung-Ho Memorial Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

1 Recruiting

Condition/Disease

Locally Advanced or Metastatic Urothelial Carcinoma

Objectives

Primary Objectives - To compare pembrolizumab + lenvatinib to pembrolizumab + placebo with respect to PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). - To compare pembrolizumab + lenvatinib to pembrolizumab + placebo with respect to overall survival (OS).

Test Drug

Lenvatinib
Pembrolizumab

Active Ingredient

Lenvatinib
Pembrolizumab

Dosage Form

capsule
injection

Dosage

4 mg、10 mg
100 mg

Endpoints

Primary Endpoints
- Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to PFS per RECIST 1.1 by BICR. PFS, defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first.
- Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to OS. OS, defined as the time from
randomization to the date of death from any cause.

Inclution Criteria

1. Have a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial carcinoma of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
2. Have at least 1 measurable target lesion per RECIST 1.1 as assessed by the local site investigator/radiologist.
3. Have provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated and adequate for PD-L1 evaluation.
4. Have received no prior systemic chemotherapy for advanced or metastatic UC with the following exceptions:
* Neoadjuvant platinum-based chemotherapy for treatment of muscleinvasive bladder cancer with recurrence >12 months from completion of the therapy is permitted.
* Adjuvant platinum-based chemotherapy following radical cystectomy, with recurrence >12 months from completion of the therapy, is permitted.
5. Meet criteria for either option a or option b (below):
a. Have a tumor(s) with PD-L1 CPS ≥10 and be considered ineligible to receive cisplatin-based combination therapy, based on 1 of the following:
• ECOG PS 2 (Protocol Appendix 9) within 7 days prior to randomization
• CrCl (calculated or measured using the institutional standard) ≥30 to ≤60 mL/min
• NCI CTCAE Version 4.0 Grade ≥2 audiometric hearing loss (25 dB in 2 consecutive frequency ranges)
• NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy
OR
b. In the opinion of the investigator, be considered ineligible to receive any platinum-based chemotherapy (ie, ineligible for cisplatin and carboplatin) based on:
• ECOG PS 2 within 7 days prior to randomization.
and at least 1 of the following:
• Documented visceral metastatic disease
• CrCl ≥30 to ≤60 mL/min
• NCI CTCAE Version 4.0 Grade ≥2 audiometric hearing loss
• NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy
• Other reason, identified on the case report form (CRF), for the participant’s being unable to receive 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.
Note: The reason(s) for ineligibility for cisplatin or any platinum-based chemotherapy must be documented in the participant’s medical record and on the electronic case report form (eCRF).
6. Be male or female and ≥18 years of age and considered an adult per local regulations on the day of signing the informed consent.
7. Have ECOG PS 0, 1, or 2 within 7 days prior to randomization and a life expectancy of ≥3 months.
8. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 95 days after the last dose of pembrolizumab or lenvatinib/placebo and refrain from donating sperm during this period:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause [Protocol Appendix 5]) as detailed below:
• Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a 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.
9. A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies:
• Is not a WOCBP.
OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year) with low user dependency, or be abstinent from heterosexual intercourse as her preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Protocol Appendix 5 during the intervention period and for at least 120 days after
the last dose of pembrolizumab or lenvatinib/placebo. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 72 hours before the first dose of study intervention.
• If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Additional requirements for pregnancy testing during and after study intervention are in Protocol Appendix 2.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk of including a woman with an early undetected pregnancy.
10. The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
11. Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤140/90 mm Hg at screening and no change in antihypertensive medications within 1 week prior to randomization.
12. Have adequate organ function.

Exclusion Criteria

1. Has disease that is suitable for local therapy administered with curative intent (eg, chemotherapy and radiation for Stage 3 disease).
2. Has tumor with any neuroendocrine or small cell component.
3. Has a history of a gastrointestinal condition or procedure (eg, gastric bypass, malabsorption) that, in the opinion of the investigator, may affect oral drug absorption.
4. Has had major surgery within 4 weeks prior to the first dose of study intervention.
Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
5. Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
6. Has radiographic evidence of major blood vessel invasion/infiltration, or has had clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks prior to the first dose of study intervention.
The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
7. Has had significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of 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.
8. Has known intolerance or severe hypersensitivity (Grade ≥3) to pembrolizumab or lenvatinib or any of their excipients.
9. Has received lenvatinib as monotherapy or in combination with a PD-1/PD-L1 inhibitor or has previously been enrolled in a clinical study evaluating lenvatinib for bladder cancer, regardless of the treatment received.
10. Is a WOCBP who has a positive urine pregnancy test within 24 hours before randomization (see Protocol Appendix 5). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy test result is positive. If >24 hours have elapsed between the screening pregnancy test and the first dose of study intervention, another pregnancy test (urine or serum) must be performed and must be negative for the participant to start receiving study intervention.
11. 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 (eg, CTLA-4, OX 40, CD137), or any other antibody or drug targeting T-cell costimulatory pathways in the adjuvant or advanced/metastatic setting.
12. Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study intervention, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study intervention. Participants must have recovered from all radiation-related toxicities, and must
not require corticosteroids.
13. Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
14. In the investigator’s judgment, has not recovered from toxicity or other complications from any major surgery prior to starting study intervention.
15. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
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.
16. Has an LVEF below the institutional normal range, as determined by MUGA or ECHO.
17. Has history or presence of an abnormal ECG that, in the investigator’s opinion, is clinically meaningful. Participants with QTcF >480 msec are excluded. If a single QTcF is >480 msec, the participant may be enrolled if the average QTcF for 3 ECGs is <480 msec.
18. 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.
19. 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 (eg, breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded.
• A history of prostate cancer (T2NXMX or lower with Gleason score ≤7) treated with definitive intent (surgically or with radiation therapy) at least 1 year prior to study entry is acceptable, provided that the participant is considered prostate cancer-free and the following criteria are met:
• Participants who have undergone radical prostatectomy must have undetectable prostate-specific antigen (PSA) for >1 year and at screening.
• Participants who have had radiation must have a PSA doubling time >1 year (based on at least 3 values determined >1 month apart) and a total PSA value which does not meet Phoenix criteria for biochemical recurrence (ie, <2.0 ng/mL above nadir).
• Participants with untreated low-risk prostate cancer (Gleason score ≤6) on active surveillance with PSA doubling time >1 year (based on at least 3 values determined >1 month apart) are also eligible.
20. Has central nervous system (CNS) metastases, unless the participant has completed local therapy (eg, whole brain radiation therapy, surgery, or radiosurgery) and has discontinued use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of CNS metastases must be stable for at least 4 weeks
before starting study intervention.
21. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Brief (<7 days) use of systemic corticosteroids is allowed when use is considered SOC.
• Participants with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will be an
exception to this rule.
• Participants requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded.
• Participants with hypothyroidism that is stable with hormone replacement or Sjøgren’s syndrome will not be excluded.
22. Has a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis.
23. Has an active infection requiring systemic therapy.
24. Has a known history of human immunodeficiency virus (HIV) infection. Testing is not required unless mandated by the local health authority.
25. Has a known history of or is positive for active hepatitis B (hepatitis B surface antigen [HbsAg] reactive) or has active hepatitis C (HCV RNA). Testing is not required unless mandated by the local health authority.
26. Has active tuberculosis.
27. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
28. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
29. Is receiving hemodialysis.
30. A participant with >1+ proteinuria on urinalysis at screening will undergo 24- hour urine collection for quantitative assessment of proteinuria. A participant with urine protein ≥1 g/24 h will be excluded.
31. 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.
32. Has had an allogeneic tissue/solid organ transplant.

The Estimated Number of Participants

  • Taiwan

    35 participants

  • Global

    694 participants

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