Back to Clinical Trials

Brief Title: A Substudy of Investigational Agents in Programmed Cell Death-1/Ligand 1 (PD-1/L1) Refractory Locally Advanced or Metastatic Urothelial Carcinoma (mUC) (MK-3475-04A)

A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A


  • Org Study ID: 3475-04A
  • Secondary ID: N/A
  • NCT ID: NCT05562830
  • Sponsor: Merck Sharp & Dohme LLC


This substudy is part of an umbrella platform study which is designed to evaluate investigational agents with or without pembrolizumab in participants with urothelial carcinoma who are in need of new treatment options. Substudy 04A will enroll participants with locally advanced or mUC whose disease is resistant to treatment with programmed cell death-1/ligand 1 (PD-1/L1) inhibitors. The protocol infrastructure will enable the rolling assignment of investigational treatments.

  • Overall Status
    Active, not recruiting
  • Start Date
    November 16, 2022
  • Phase
  • Study Type


Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A


  • Urothelial Carcinoma


Inclusion Criteria:
The main inclusion and exclusion criteria include but are not limited to the following:
* Histologically or cytologically confirmed diagnosis of locally advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.

- * PD-1/L1 refractory locally advanced or mUC as evidenced by:
EITHER disease progression while on treatment or after treatment with an anti-PD-1/L1 monoclonal antibody (mAb) for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies OR disease recurrence while on treatment or after treatment with an anti-PD-1/L1 mAb for muscle-invasive urothelial carcinoma (MIUC) administered as monotherapy.
* Participants 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.
Exclusion Criteria:
* Known additional nonurothelial malignancy that is progressing or has required active treatment within 3 years prior to study randomization/allocation.

- * Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation.

- * Active infection requiring systemic therapy.

- * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.

- * Known history of human immunodeficiency virus (HIV).

- * Known history of hepatitis B or known hepatitis C virus infection.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No


Name: Medical Director

Role: Study Director

Affiliation: Merck Sharp & Dohme LLC

Overall Contact

Name: N/A

Phone: N/A

Email: N/A


Facility Status Contact