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Urothelial CarcinomaPhase 2NCT05923190

Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

A Phase 2 study testing Enfortumab vedotin and Pembrolizumab in people with Urothelial Carcinoma and Metastatic Urothelial Carcinoma, run by Fox Chase Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a non-randomized two arm open-label phase 2 pilot study in adult subjects with locally advanced or metastatic urothelial cancer. The study will investigate an alternative administration schedule of EV given as monotherapy and in combination with pembrolizumab. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Enfortumab vedotin and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteUnited States
Study dates
14 Jun 2023to 1 Jul 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • EV monotherapy main cohort:
  • Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
  • Planned to receive EV as standard treatment for advanced urothelial cancer
  • ECOG performance status 0-2
  • Prior systemic therapy must have completed at least 14 days prior to initiating therapy.
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  • Age > 18 years.
  • Ability to understand and willingness to sign a written informed consent and HIPAA consent document
  • Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin-fixed paraffin-embedded [FFPE] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
  • Normal organ and marrow function as defined below.
  • Absolute neutrophil count > 1,000/mm3 unless patient has constitutional neutropenia
  • Platelets > 100,000/ul
  • Hemoglobin > 8.0 g/dL
  • Alanine transaminase (ALT) and aspartate transaminase (AST) <2.5X upper limit of normal (ULN) or <3.5X ULN if liver metastases
  • Creatinine Clearance >20 ml/min
  • EV/pembrolizumab arm:
  • Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
  • Planned to receive EV/pembrolizumab as standard treatment for advanced urothelial cancer
  • ECOG performance status 0-2
  • Prior systemic therapy must have completed at least 14 days prior to initiating therapy.
  • Age > 18 years.
  • Ability to understand and willingness to sign a written informed consent and HIPAA consent document
  • Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin fixed, paraffin embedded [FFPE] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
  • Normal organ and marrow function as defined below.
  • Absolute neutrophil count > 1,000/mm3 unless patient has constitutional neutropenia
  • Platelets > 100,000/ul
  • Hemoglobin > 8.0 g/dL
  • ALT and AST <2.5X ULN or <3.5X ULN if liver metastases
  • Creatinine Clearance >20 ml/min

Who cannot join

  • Both EV monotherapy and EV/pembrolizumab arms:
  • Patients who have received prior monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs) for urothelial cancer.
  • Grade 2 or higher baseline sensory or motor neuropathy.
  • Uncontrolled diabetes (HbA1c >8%)
  • Patients with uncontrolled and untreated central nervous system (CNS) metastases.
  • Prior radiation to CNS metastases is permitted.
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  • Prior history of CNS disease that has responded to previous systemic therapy is permitted only if no recurrence.
  • Patient should not have leptomeningeal disease
  • CNS metastases have been clinically stable for at least 6 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis.
  • If requiring steroid treatment for CNS metastases, the patient is on stable dose < 20 mg/day of prednisone or equivalent for at least 2 weeks prior to starting treatment
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug that cannot be watched and requires treatment, or any evidence of residual disease from a previously diagnosed malignancy that cannot be watched and requires treatment. Adjuvant hormonal therapy for breast cancer is allowed.
  • Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.
  • Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with enfortumab vedotin.
  • History of idiopathic pulmonary fibrosis; organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
  • Prior allogeneic stem cell or solid organ transplant.
  • Other underlying medical condition that, in the opinion of the investigator, would impair the ability of the patient to receive or tolerate the planned treatment and follow-up; any known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
  • Patients with active tuberculosis.
  • Pregnant or breast feeding
  • EV/Pembrolizumab exploratory arm only:
  • Patients who received prior immunotherapy for metastatic urothelial carcinoma (mUC) or for an alternative malignancy are eligible unless they developed an immune related adverse event while on therapy requiring cessation of therapy or use of disease modifying agents, corticosteroids, or immunosuppressive drugs.
  • History of autoimmune diseases. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
  • Patients with vitiligo or residual autoimmune hypothyroidism on stable doses of hormone replacement are permitted to enroll.
  • Patients with type 1 diabetes mellitus (T1DM) on a stable dose of insulin are permitted to enroll.
  • Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • On high dose steroids at the time of study enrollment, defined as >20mg prednisone (or bioequivalent), including steroids used for management of intracranial lesions. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fox Chase Cancer Center - Philadelphia

    Philadelphia, Pennsylvania, 19111-2497

Other trials in United States

About this study

Official title: A Pilot Trial of Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

This is a non-randomized two arm open-label phase 2 pilot study in adult subjects with locally advanced or metastatic urothelial cancer. The study will investigate an alternative administration schedule of EV given as monotherapy and in combination with pembrolizumab.

Read the detailed description

This is a non-randomized two arm open-label phase 2 pilot study in adult subjects with locally advanced or metastatic urothelial cancer. The study will investigate an alternative administration schedule of EV given as monotherapy and in combination with pembrolizumab. Approximately 50 patients will be enrolled to the main EV monotherapy cohort who are scheduled to receive EV as standard of care. Additionally, an exploratory arm will enroll 20 patients with metastatic urothelial cancer who are scheduled to receive EV in combination with pembrolizumab as standard of care. All subjects will have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and meet baseline laboratory data as outlined in the section 4.1.

Being tested
Enfortumab vedotin, Pembrolizumab
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Enfortumab vedotinDrug

    EV will be administered at standard dose of 1.25 mg/kg IV on days 1 and 8 with pembrolizumab 200 mg IV on day 1 of a 21-day cycle for 6 cycles

  • PembrolizumabDrug

    Pembrolizumab will be administered on day 1 of a 21-day cycle

Study groups in NCT05923190
Study groupRoleWhat they receive
Enfortumab vedotin (EV) monotherapyActive comparatorEV will be administered at standard dose of 1.25 mg/kg IV on days 1, 8 and 15 of a 28-day cycle for 3 cycles. First schedule de-escalation of EV will occur in patients with disease control per RECIST v1.1 (complete response/partial response/stable disease) on their first scan in the EV at 12 weeks. In these patients, EV will be administered on days 1 and 15 of a 28-day cycle. Second schedule de-escalation of EV will occur in patients with disease control per RECIST v1.1 (complete response/partial response/stable disease) on their second scan in the EV monotherapy (at 24 weeks). EV will be administered on day 1 of a 21-day cycle.
Receives: Drug: Enfortumab vedotin
EV/pembrolizumabExperimentalEV will be administered at standard dose of 1.25 mg/kg IV on days 1 and 8 with pembrolizumab 200 mg IV on day 1 of a 21-day cycle for 6 cycles. Radiographic assessment will be conducted every 9 weeks. Schedule de-escalation of EV will occur in patients with disease control per RECIST v1.1 (complete response/partial response/stable disease) on their first scan in the EV/pembrolizumab arm at 9 weeks. In these patients EV and pembrolizumab will be administered on day 1 of a 21-day cycle.
Receives: Drug: Enfortumab vedotin; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Duration of clinical benefit

    Duration of Clinical Benefit (DoCB) in patients undergoing EV schedule de-escalation in the EV monotherapy cohort. DoCB is defined as time from initiating treatment to disease progression or death in patients who achieve complete response, partial response, or stable disease (per RECIST v1.1)

    Measured: 8 months

Secondary outcomes (2)

  1. Overall survival

    Overall survival (OS) in patients undergoing EV schedule de-escalation in the EV monotherapy cohort

    Measured: 5 years

  2. Time to next treatment

    Time to Next Treatment in patients undergoing EV schedule de-escalation in the EV monotherapy

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2023
  2. Study start14 Jun 2023
  3. Primary completion1 Jul 2028 (estimated)
  4. Study completion1 Jul 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05923190
Sponsor's protocol ID
23-1008
Other IDs
GU-217
Status last verified
Mar 2026
First submitted
20 Jun 2023
Last updated
19 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enfortumab vedotin and Pembrolizumab in people with Urothelial Carcinoma and Metastatic Urothelial Carcinoma, run by Fox Chase Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Duration of clinical benefit (time frame: 8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05923190.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.

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