A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04)

Last updated: February 6, 2025
Sponsor: Merck Sharp & Dohme LLC
Overall Status: Active - Not Recruiting

Phase

1/2

Condition

Carcinoma

Urothelial Cancer

Urothelial Tract Cancer

Treatment

Coformulated favezelimab/pembrolizumab

Coformulated vibostolimab/pembrolizumab

EV

Clinical Study ID

NCT05845814
3475-04B
MK-3475-04B
2022-001371-14
  • Ages > 18
  • All Genders

Study Summary

This study is a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the efficacy and safety of coformulated favezelimab/pembrolizumab plus EV and coformulated vibostolimab/pembrolizumab plus EV relative to pembrolizumab plus EV. There will be no comparison of coformulated favezelimab/pembrolizumab plus EV versus coformulated vibostolimab/pembrolizumab plus EV. If ORR and/or DRR are substantially better on coformulated favezelimab/pembrolizumab plus EV and/or coformulated vibostolimab/pembrolizumab plus EV compared with pembrolizumab plus EV, after evaluation of the totality of data, the sponsor might consider Part 2 (expansion) to further characterize the efficacy and safety of the treatment arms under study.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Must have histologically documented, locally advanced/metastatic urothelialcarcinoma (la/mUC).

  • Participants with mixed histology are eligible provided the urothelialcomponent is ≥50% (and <10% plasmacytoid component)

  • Participants whose tumors contain any neuroendocrine component are not eligible (variant histology to be confirmed locally)

  • Must not have received prior systemic therapy for la/mUC. The following therapies inearlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) arepermitted:

  • Participants that received neoadjuvant or adjuvant chemotherapy are permitted.

  • Participants who received anti- programmed cell death 1 protein (PD-1) orprogrammed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg, NMIBC, MIUC) with progression/recurrence >12 months from completion oftherapy are permitted.

  • Must provide an archival tumor tissue sample or newly obtained core or excisionalbiopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequatefor biomarker evaluation. A newly obtained biopsy is strongly preferred, but notrequired if archival tissue is evaluable.

  • Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 orbaseline. Endocrine-related AEs adequately treated with hormone replacement or with <Grade 2 neuropathy are eligible.

Exclusion

Exclusion Criteria:

  • Has a known additional malignancy, except if the participant has undergonepotentially curative therapy with no evidence of that disease recurrence for atleast 3 years since initiation of that therapy.

  • Central nervous system (CNS) metastases are permitted on-study if all of thefollowing are true: a) CNS metastases have been clinically stable for at least 4weeks prior to screening and baseline scans show no evidence of new or enlargedmetastasis; b) the participant is on a stable dose of ≤10 mg/day of prednisone orequivalent for at least 2 weeks (if requiring steroid treatment); c) participantdoes not have leptomeningeal disease.

  • Has received a live or live-attenuated vaccine within 30 days prior to the firstdose of study intervention.

  • Has received an investigational agent or has used an investigational device within 4weeks prior to study intervention administration.

  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapyor any other form of immunosuppressive therapy within 7 days prior the first dose ofstudy intervention. Inhaled or topical steroids are permitted in the absence ofactive autoimmune disease. Physiologic replacement doses of corticosteroids arepermitted for participants with adrenal insufficiency.

  • Has active keratitis or corneal ulcerations. Superficial punctate keratitis isallowed if the disorder is being adequately treated in the opinion of theinvestigator.

  • Has an active autoimmune disease that has required systemic treatment in past 2years except replacement therapy.

  • Has a history of uncontrolled diabetes.

  • Has a history of (noninfectious) pneumonitis that required steroids or has currentpneumonitis

  • Has an active infection (viral, bacterial, or fungal) requiring systemic therapy.

  • Has a known history of human immunodeficiency virus (HIV) infection.

  • Has hepatitis B or hepatitis C virus infection.

  • Has had major surgery within 4 weeks prior to first dose of study intervention.

  • Has had an allogenic tissue/solid organ transplant

Study Design

Total Participants: 390
Treatment Group(s): 4
Primary Treatment: Coformulated favezelimab/pembrolizumab
Phase: 1/2
Study Start date:
June 23, 2023
Estimated Completion Date:
May 31, 2027

Study Description

The master study for this substudy is MK-3475-U04/KEYMAKER-U04. The master study will not be screening any participants and will not be registered.

With Amendment 2, participants will discontinue treatment with coformulated vibostolimab/pembrolizumab (Arm B) and be transitioned to pembrolizumab only. Per protocol, no analysis of Part 2 primary or secondary outcome measures (including efficacy or safety) will occur since Part 2 of the study will no longer take place.

Connect with a study center

  • Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si

    Brisbane, Queensland 4029
    Australia

    Site Not Available

  • Austin Health-Cancer Clinical Trials Centre ( Site 3950)

    Heidelberg, Victoria 3084
    Australia

    Site Not Available

  • The Ottawa Hospital - General Campus-The Ottawa Hospital Cancer Centre ( Site 3105)

    Ottawa, Ontario K1H 8L6
    Canada

    Site Not Available

  • Princess Margaret Cancer Centre ( Site 3106)

    Toronto, Ontario M5G 2M9
    Canada

    Site Not Available

  • Sunnybrook Research Institute - Odette Cancer Centre ( Site 3108)

    Toronto, Ontario M4N 3M5
    Canada

    Site Not Available

  • Bradfordhill-Clinical Area ( Site 3155)

    Santiago, Region M. De Santiago 8420383
    Chile

    Site Not Available

  • FALP-UIDO ( Site 3151)

    Santiago, Region M. De Santiago 7500921
    Chile

    Site Not Available

  • ONCOCENTRO APYS-ACEREY ( Site 3158)

    Viña del Mar, Valparaiso 2520598
    Chile

    Site Not Available

  • Bradford Hill Norte ( Site 3152)

    Antofagasta, 1240000
    Chile

    Site Not Available

  • Centro de Investigación Oncológica del Norte ( Site 3152)

    Antofagasta, 1240000
    Chile

    Active - Recruiting

  • CHU de Bordeaux Hop St ANDRE ( Site 3607)

    Bordeaux, Aquitaine 33075
    France

    Site Not Available

  • Centre Georges François Leclerc-Centre de recherche clinique ( Site 3608)

    Dijon, Cote-d Or 21079
    France

    Site Not Available

  • Oncopole Claudius Regaud ( Site 3610)

    Toulouse, Haute-Garonne 31059
    France

    Site Not Available

  • Hôpital Européen Georges Pompidou ( Site 3605)

    Paris, Ile-de-France 75015
    France

    Site Not Available

  • centre hospitalier lyon sud ( Site 3606)

    Pierre-Bénite, Rhone 69310
    France

    Site Not Available

  • Rambam Health Care Campus-Oncology Division ( Site 3501)

    Haifa, 3109601
    Israel

    Site Not Available

  • Rabin Medical Center-Oncology ( Site 3504)

    Petah Tikva, 4941492
    Israel

    Site Not Available

  • Sheba Medical Center-ONCOLOGY ( Site 3503)

    Ramat Gan, 5265601
    Israel

    Site Not Available

  • Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3405)

    Milan, Lombardia 20133
    Italy

    Site Not Available

  • Ospedale San Raffaele-Oncologia Medica ( Site 3403)

    Milano, Lombardia 20132
    Italy

    Site Not Available

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 3406)

    Napoli, 80131
    Italy

    Site Not Available

  • Asan Medical Center-Department of Oncology ( Site 3901)

    Seoul, 05505
    Korea, Republic of

    Site Not Available

  • Samsung Medical Center ( Site 3902)

    Seoul, 06351
    Korea, Republic of

    Site Not Available

  • Severance Hospital, Yonsei University Health System-Medical oncology ( Site 3903)

    Seoul, 03722
    Korea, Republic of

    Site Not Available

  • Maastricht UMC+ ( Site 3304)

    Maastricht, Limburg 6229 HX
    Netherlands

    Site Not Available

  • Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 3302)

    Amsterdam, Noord-Holland 1066 CX
    Netherlands

    Site Not Available

  • Erasmus Medisch Centrum-Medical Oncology ( Site 3303)

    Rotterdam, Zuid-Holland 3015 GD
    Netherlands

    Site Not Available

  • Hospital Universitari Vall d'Hebron ( Site 3767)

    Barcelona, 08035
    Spain

    Site Not Available

  • Hospital Clinico San Carlos ( Site 3765)

    Madrid, 28040
    Spain

    Site Not Available

  • Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 3802)

    Kaohsiung, 83301
    Taiwan

    Site Not Available

  • National Cheng Kung University Hospital-Clinical Trial Center ( Site 3803)

    Tainan, 704
    Taiwan

    Site Not Available

  • National Taiwan University Hospital-Oncology ( Site 3801)

    Taipei, 10002
    Taiwan

    Site Not Available

  • ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 3201)

    London, London, City Of SW3 6JJ
    United Kingdom

    Site Not Available

  • St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 3206)

    London, London, City Of EC1A 7BE
    United Kingdom

    Site Not Available

  • Moores Cancer Center ( Site 3028)

    La Jolla, California 92093
    United States

    Site Not Available

  • University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 3045)

    Orange, California 92868
    United States

    Site Not Available

  • Anschutz Cancer Pavilion ( Site 3017)

    Aurora, Colorado 80045
    United States

    Site Not Available

  • Emory University School of Medicine ( Site 3043)

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • Indiana University Melvin and Bren Simon Cancer Center ( Site 3011)

    Indianapolis, Indiana 46202
    United States

    Site Not Available

  • Washington University School of Medicine ( Site 3038)

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Icahn School of Medicine at Mount Sinai ( Site 3018)

    New York, New York 10029
    United States

    Site Not Available

  • Memorial Sloan Kettering Cancer Center ( Site 3031)

    New York, New York 10065
    United States

    Site Not Available

  • Cleveland Clinic-Taussig Cancer Center ( Site 3036)

    Cleveland, Ohio 44195
    United States

    Site Not Available

  • UPMC Hillman Cancer Center ( Site 3014)

    Pittsburgh, Pennsylvania 15232
    United States

    Site Not Available

  • Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 3041)

    Salt Lake City, Utah 84112
    United States

    Site Not Available

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