Enfortumab Vedotin Plus Pembrolizumab With Selective Bladder Sparing for Treatment of Muscle-invasive Bladder Cancer

February 19, 2026 updated by: Matthew Galsky

Phase 2 Trial of Enfortumab Vedotin Plus Pembrolizumab With Selective Bladder Sparing for Treatment of Muscle-invasive Urothelial Cancer of the Bladder

Patients with MIBC will receive 3 cycles (C1-C3) of induction enfortumab vedotin plus pembrolizumab followed by restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies using a recommended template. Patients achieving a stringently defined cCR (clinical complete response) will receive 14 cycles of "maintenance" treatment. Enfortumab vedotin will be administered during the first 6 cycles (C4-C9) of "maintenance" treatment and pembrolizumab will be given all 14 cycles (C4-C14). Patients with any residual disease at clinical restaging (i.e., >cTa disease) will undergo cystectomy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
47

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
        • Principal Investigator:
          • Abhishek Tripathi, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Tareq Salous, MD
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Principal Investigator:
          • Alexander Wei, MD
        • Contact:
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Principal Investigator:
          • Matthew Galsky, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
        • Contact:
        • Principal Investigator:
          • Elizabeth Plimack, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  2. Age ≥ 18 years at the time of consent.
  3. ECOG Performance Status of 0-1 within 28 days prior to registration.
  4. Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder clinical stage T2-3N0M0. Participants with mixed histology are eligible provided the urothelial component is ≥50% with the following exceptions: (a) tumors with any degree of squamous differentiation are eligible provided there is a urothelial cancer component, (b) tumors that contain any component of neuroendocrine histology are not eligible. N0 will be considered as the absence of radiographically enlarged lymph nodes on baseline imaging (i.e., Patients with lymph nodes ≥1 cm in short axis on imaging are not eligible).
  5. Have undergone a standard of care maximal transurethral resection of bladder tumor ≤ 90 days prior C1D1. A maximal TURBT should be performed when feasible and is defined as a macroscopically complete resection of bladder tumor.
  6. All subjects must have adequate transurethral resection of bladder tumor tissue available for submission identified during screening. The specimen must include tumor tissue (i.e., if a restaging maximal TURBT was performed and there was no cancer in the specimen, tissue from the most recent prior TURBT that established the diagnosis of muscle-invasive urothelial cancer of the bladder should be submitted). Tissue from both the restaging TURBT and the prior diagnostic TURBT may be requested. Subjects without available archival tissue must be discussed with the sponsor-investigator.
  7. Be deemed eligible to undergo radical cystectomy and pelvic lymph node dissection

  8. Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.

    • Absolute neutrophil count (ANC): ≥ 1.5 x 10^9/L
    • Hemoglobin (Hgb): ≥ 9 g/dL
    • Platelets: ≥ 100 x 10^9/L
    • Creatinine clearance: ≥ 30 mL/min
    • Bilirubin: ≤ 1.5 ×ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN
    • Aspartate aminotransferase (AST): ≤ 2.5 × ULN
    • Alanine aminotransferase (ALT): ≤ 2.5 × ULN
    • International normalized ratio (INR) or Prothrombin time (PT) or Partial thromboplastin time (PTT): ≤ 1.5 ×ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range for intended use of anticoagulants

10. Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. WOCBP must agree to use contraception.

11. Male participants able to father a child who are sexually active with female of childbearing potential must be willing to use an effective method(s) of contraception.

Exclusion Criteria:

  1. Pre-existing sensory or motor neuropathy Grade ≥ 2
  2. Ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
  3. Prior systemic chemotherapy for muscle-invasive urothelial cancer of the bladder.
  4. Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured. Patients with intermediate or lower risk prostate cancer as defined by the National Comprehensive Cancer Network (NCCN) risk stratification guidelines may be eligible for enrollment.
  5. Prior radiation therapy for bladder cancer.
  6. Hemoglobin A1c ≥ 8% or hemoglobin A1c 7%-<8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
  7. Active infection requiring systemic therapy.
  8. Known active Hepatitis B or C infection. NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  9. HIV-infected patients on effective anti-retroviral therapy with an undetectable viral load are eligible.
  10. Has a known history of active TB (Bacillus Tuberculosis).
  11. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  12. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  13. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
  14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  15. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab or enfortumab vedotin and/or any of their excipients.
  16. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  17. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  19. Has had an allogenic tissue/solid organ transplant.
  20. Is currently receiving an investigational agent or has received an investigational agent or used an investigational device within 28 days of study registration.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Enfortumab vedotin plus pembrolizumab
Patients with MIBC will receive 3 cycles (C1-C3) of induction enfortumab vedotin (1.25 mg/kg for a maximum dose of 125 mg) plus pembrolizumab (200 mg) followed by restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies using a recommended template. Patients achieving a stringently defined cCR (defined below) will receive 14 cycles of "maintenance" treatment. Enfortumab vedotin (1.25 mg/kg for a maximum dose of 125 mg) will be administered during the first 6 cycles (C4-C9) of "maintenance" treatment and pembrolizumab (200 mg) will be given all 14 cycles (C4-C14). Patients with any residual disease at clinical restaging (i.e., >cTa disease) will undergo cystectomy.
Drug: Pembrolizumab
200 mg
Drug: Enfortumab vedotin
1.25 mg/kg (maximum dose 125 mg)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Complete response rate with enfortumab vedotin plus pembrolizumab for MIBC
Time Frame: 9 weeks
Clinical complete response rate will be defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab
9 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety of enfortumab vedotin plus pembrolizumab
Time Frame: 2 years
Safety will be determined according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5
2 years
Positive predictive value (PPV) of cCR Patients
Time Frame: 2 years
Estimate the positive predictive value (PPV) of cCR for 2-year bladder-intact event-free survival
2 years
Local recurrence-free survival
Time Frame: 4 years
Estimate invasive local recurrence-free survival in patients achieving a clinical complete response and forgoing immediate cystectomy. Local recurrence free survival is defined as the time from initiation of treatment until the development of invasive local recurrences in the intact bladder.
4 years
Association between clinical complete response (cCR) and bladder-intact event-free survival
Time Frame: 4 years
Estimate association between clinical complete response defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab and bladder-intact event-free survival defined from initiation of treatment until radical cystectomy, evidence of unresectable or metastatic disease, or death due to any cause based on the Kaplan-Meier method .
4 years
Association between clinical complete response (cCR) and recurrence-free survival
Time Frame: 4 years
Estimate association between clinical complete response defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab and recurrence free survival defined as the time from initiation of treatment until the development of invasive local recurrences in the intact bladder based on the Kaplan-Meier method.
4 years
Association between clinical complete response (cCR) and metastasis-free survival
Time Frame: 4 years
Estimate association between clinical complete response defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab and metastasis-free survival defined as the time from initiation of treatment to the development of metastatic disease based on the Kaplan-Meier method.
4 years
Association between clinical complete response (cCR) and overall survival
Time Frame: 4 years
Estimate association between clinical complete response defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab and overall survival defined as the time from initiation of treatment to date of death from any cause based on the Kaplan-Meier method.
4 years
Bladder-intact event-free survival
Time Frame: 4 years
Bladder-intact event-free survival is defined from initiation of treatment until radical cystectomy, evidence of unresectable or metastatic disease, or death due to any cause. Bladder-intact event-free survival will be estimated in patients achieving a clinical complete response.
4 years
Pathologic stage
Time Frame: 4 years
Pathologic stage will be defined based on TNM staging of the cystectomy specimen. Pathologic stage will be explained in patients who did not achieve a clinical complete response and in patients achieving a clinical complete response who subsequently undergo cystectomy.
4 years
Metastasis-free survival
Time Frame: 4 years
Metastasis-free survival is defined as the time from initiation of treatment to the development of metastatic disease. Microscopic metastatic disease involving regional lymph nodes resected at cystectomy performed with curative intent will not be considered an event. Metastasis-free survival will be estimated in patients achieving a clinical complete response, in patients not achieving a clinical complete response, and in the overall cohort.
4 years
Overall survival
Time Frame: 4 years
Overall survival is defined as the time from initiation of treatment to date of death from any cause. Overall survival will be estimated in patients achieving a clinical complete response, in patients not achieving a clinical complete response, and in the overall cohort.
4 years
Positive predictive value (PPV) of cCR Patients
Time Frame: 2 years
Estimate the positive predictive value (PPV) of cCR for 2-year metastasis-free survival
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Matthew Galsky

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC
Icahn School of Medicine at Mount Sinai
Astellas Pharma Inc
Seagen Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Matthew Galsky, MD, Sponsor-Investigator

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 7, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 17, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 30, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 5, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HCRN-GU22-598

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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