The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

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Genitourinary Cancer

Enfortumab vedotin

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
Phase 1 /2
NCT05562830

Active Not-enrolling

Globe
Locations

United States, Australia, Chile, Denmark, Israel, Korea, Republic of, Spain

Study design

Participant Group/Arm

EXPERIMENTAL: Zilovertamab vedotin

Participants will receive zilovertamab vedotin 2mg/kg administered on Day 1 and Day 8 of each 3 week cycle (Q3W) until documented disease progression or any other discontinuation criterion is met.

Intervention/Treatment

BIOLOGICAL: Zilovertamab vedotin

Administered via intravenous (IV) infusion on day 1 and day 8 of Q3W cycles

Key eligibility criteria

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.

Key dates

Study start date
  • November 2022
Estimated primary completion date
  • October 2027

Key endpoints

Primary Outcome Measures
Outcome Measure

Percentage of Participants Who Experienced At Least One Adverse Event (AE)

Measure Description

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

Time Frame

Up to approximately 5 years

Outcome Measure

Percentage of Participants Who Discontinued Study Treatment Due to an AE

Measure Description

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment

Time Frame

Up to approximately 5 years

Outcome Measure

Objective Response Rate (ORR)

Measure Description

ORR is defined as the percentage of participants who achieve a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

Time Frame

Up to approximately 2 years

Secondary Outcome Measures:
Outcome Measure

Duration of Response (DOR)

Measure Description

For participants who demonstrate confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.

Time Frame

Up to approximately 2 years

Number of participants

40

Collaborators and investigators

Sponsor: Merck Sharp & Dohme LLC

Collaborator: None

This information is current as of July 3rd 2023.