A Study of Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab in Advanced Urothelial Carcinoma (MK-3475-04C/KEYMAKER-U04)
NCT ID: NCT06483334
Last Updated: 2025-12-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
38 participants
INTERVENTIONAL
2024-07-17
2028-03-31
Brief Summary
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Detailed Description
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As of Amendment 5, Part 2 will not be conducted. No participants will be enrolled in Part 2, and no data for Part 2 will be collected.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Sacituzumab tirumotecan plus EV
Participants will receive sacituzumab tirumotecan as an intravenous (IV) infusion and EV as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.
Sacituzumab tirumotecan
IV infusion at different dose levels
Enfortumab Vedotin
IV infusion at different dose levels
Supportive care measures
Participants are allowed to take supportive care measures at the discretion of the investigator. Prophylactic supportive care measures may include but are not limited to antiemetic agents, antidiarrheal agents, granulocyte and erythroid growth factors, and blood transfusions.
Sacituzumab tirumotecan plus EV and pembrolizumab
Participants will receive sacituzumab tirumotecan as an IV infusion and EV as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision. Participants will also receive pembrolizumab 200 mg as an IV infusion on Day 1 of every 3-week cycle for up to \~2 years (35 cycles).
Sacituzumab tirumotecan
IV infusion at different dose levels
Enfortumab Vedotin
IV infusion at different dose levels
Pembrolizumab
200 mg IV infusion
Supportive care measures
Participants are allowed to take supportive care measures at the discretion of the investigator. Prophylactic supportive care measures may include but are not limited to antiemetic agents, antidiarrheal agents, granulocyte and erythroid growth factors, and blood transfusions.
Interventions
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Sacituzumab tirumotecan
IV infusion at different dose levels
Enfortumab Vedotin
IV infusion at different dose levels
Pembrolizumab
200 mg IV infusion
Supportive care measures
Participants are allowed to take supportive care measures at the discretion of the investigator. Prophylactic supportive care measures may include but are not limited to antiemetic agents, antidiarrheal agents, granulocyte and erythroid growth factors, and blood transfusions.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable.
* Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement are eligible.
* PART 1 ONLY: Participants must have received platinum-based chemotherapy for treatment of la/mUC.
* PART 1 ONLY: Participants must not have received \>2 lines of therapy for la/mUC. Platinum-based chemotherapy followed by avelumab maintenance is considered 2 lines of therapy.
* PART 2 ONLY: Participants must not have received prior systemic therapy for la/mUC.
Exclusion Criteria
* Known active central nervous system metastases and/or carcinomatous meningitis.
* Has Grade ≥2 peripheral neuropathy.
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease and/or serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention.
* Has active keratitis or corneal ulcerations. Superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator.
* Has a history of uncontrolled diabetes.
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
* PART 2 ONLY: Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
* PART 2 ONLY: Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.
* Is human immunodeficiency virus (HIV)-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has active Hepatitis B or Hepatitis C virus infection.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Has an active infection requiring systemic therapy.
* PART 2 ONLY: History of allogeneic tissue/solid organ transplant.
* Has not adequately recovered from major surgery or has ongoing surgical complications.
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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University of California San Francisco HDFCCC ( Site 4044)
San Francisco, California, United States
University of Chicago Medical Center ( Site 4037)
Chicago, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center ( Site 4011)
Indianapolis, Indiana, United States
Dana-Farber Cancer Institute ( Site 4047)
Boston, Massachusetts, United States
Siteman Cancer Center ( Site 4038)
St Louis, Missouri, United States
Icahn School of Medicine at Mount Sinai ( Site 4018)
New York, New York, United States
Cleveland Clinic-Taussig Cancer Center ( Site 4036)
Cleveland, Ohio, United States
Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 4041)
Salt Lake City, Utah, United States
The Ottawa Hospital - General Campus ( Site 4105)
Ottawa, Ontario, Canada
Princess Margaret Cancer Centre ( Site 4106)
Toronto, Ontario, Canada
Centre Hospitalier Lyon Sud ( Site 4606)
Pierre-Bénite, Auvergne-Rhône-Alpes, France
Rambam Health Care Campus ( Site 4501)
Haifa, , Israel
Rabin Medical Center-Oncology ( Site 4504)
Petah Tikva, , Israel
Sheba Medical Center-ONCOLOGY ( Site 4503)
Ramat Gan, , Israel
Ospedale San Raffaele-Oncologia Medica ( Site 4403)
Milan, Lombardy, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 4405)
Milan, , Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 4406)
Napoli, , Italy
Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 4302)
Amsterdam, North Holland, Netherlands
Severance Hospital, Yonsei University Health System-Medical oncology ( Site 4903)
Seoul, , South Korea
Asan Medical Center-Department of Oncology ( Site 4901)
Seoul, , South Korea
Samsung Medical Center ( Site 4902)
Seoul, , South Korea
Hospital Universitari Vall d'Hebron-Oncology ( Site 4767)
Barcelona, , Spain
Hospital Clinico San Carlos ( Site 4765)
Madrid, , Spain
National Cheng Kung University Hospital-Clinical Trial Center ( Site 4803)
Tainan, , Taiwan
St Bartholomew s Hospital ( Site 4206)
London, London, City of, United Kingdom
Countries
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Related Links
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Merck Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-3475-04C
Identifier Type: OTHER
Identifier Source: secondary_id
2023-506387-14-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1293-7631
Identifier Type: REGISTRY
Identifier Source: secondary_id
3475-04C
Identifier Type: -
Identifier Source: org_study_id