Status:

ACTIVE_NOT_RECRUITING

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)

Lead Sponsor:

Merck Sharp & Dohme LLC

Conditions:

Metastatic Urothelial Carcinoma

Locally Advanced Urothelial Carcinoma

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief 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 safety and preliminary efficacy of s...

Detailed 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. As of Amendment 5, Part 2 will not be conducted. No...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

July 17 2024

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

March 31 2028

Estimated Enrollment :

38 Patients enrolled

Trial Details

Trial ID

NCT06483334

Start Date

July 17 2024

End Date

March 31 2028

Last Update

January 5 2026

Active Locations (25)

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Page 1 of 7 (25 locations)

1

University of California San Francisco HDFCCC ( Site 4044)

San Francisco, California, United States, 94158

2

University of Chicago Medical Center ( Site 4037)

Chicago, Illinois, United States, 60637

3

Indiana University Melvin and Bren Simon Cancer Center ( Site 4011)

Indianapolis, Indiana, United States, 46202

4

Dana-Farber Cancer Institute ( Site 4047)

Boston, Massachusetts, United States, 02115