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Combining new therapies for advanced bladder cancer

A Phase 1/2 Randomized, Umbrella Study to Evaluate the Efficacy and Safety of MK-2870 Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab, as Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04C

PHASE1; PHASE2 · Merck Sharp & Dohme LLC · NCT06483334

This study is testing a new combination of two treatments for advanced bladder cancer to see if they are safe and effective for patients.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment98 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC (industry)
Drugs / interventionsavelumab, chemotherapy, pembrolizumab, sacituzumab, enfortumab
Locations23 sites (San Francisco, California and 22 other locations)
Trial IDNCT06483334 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of sacituzumab tirumotecan combined with enfortumab vedotin in patients with advanced urothelial carcinoma. It consists of two parts: the first part assesses the safety and preliminary efficacy of the combination, while the second part builds on these results to further evaluate the combination with pembrolizumab. Participants will provide tumor samples for biomarker evaluation, and the study aims to gather data on pharmacokinetics and safety profiles.

Who should consider this trial

Good fit: Ideal candidates are individuals with histologically documented locally advanced or metastatic urothelial carcinoma who have received prior platinum-based chemotherapy.

Not a fit: Patients who have received more than two lines of therapy for their urothelial carcinoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with advanced urothelial carcinoma.

How similar studies have performed: Other studies have shown promising results with similar combinations of therapies in treating advanced urothelial carcinoma, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

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.

Exclusion Criteria:

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 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 this trial is running

San Francisco, California and 22 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Metastatic Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Programmed Cell Death-1, Programmed Cell Death 1 Ligand 1, Programmed Cell Death 1 Ligand 2

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.