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)

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Metastatic Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma

In brief

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 safety and preliminary efficacy of sacituzumab tirumotecan plus enfortumab vedotin (EV). Part 2 will be based on Part 1 results and will evaluate the efficacy, pharmacokinetics, and safety of sacituzumab tirumotecan plus EV in combination with pembrolizumab in participants with advanced urothelial carcinoma.

Key facts

Study ID

NCT06483334

Run by

Merck Sharp & Dohme LLC

People needed

38

Starts

2024-07-17

Expected to finish

2028-03-31

Last updated by the study team

2026-02-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The main inclusion criteria include but are not limited to the following:
• Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).
• 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.

You may not qualify if…

• The main exclusion criteria include but are not limited to the following:
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• 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.

Where it is running

• 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) — Naples, 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

Full record on ClinicalTrials.gov

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