A Study to Find Out if Enfortumab Vedotin Given With Pembrolizumab Helps People With Muscle-invasive Bladder Cancer Keep Their Bladder

An Open-label, Single-Arm, Phase 2 Study to Evaluate Enfortumab Vedotin Plus Pembrolizumab for Bladder Preservation in Participants With Muscle-invasive Bladder Cancer (EV-209)

People with a type of bladder cancer called muscle-invasive bladder cancer have cancer that has spread into the muscle wall of the bladder. The standard treatment is to have chemotherapy, followed by surgery to completely remove the bladder. This has a significant impact on people with long-term life-altering changes. There are also limited options for people who cannot have chemotherapy or who do not want their bladder removed.

Studies show that enfortumab vedotin, when given with pembrolizumab, can help people with advanced bladder cancer. This treatment has also worked well for people with muscle-invasive bladder cancer who can't receive chemotherapy when it was given before and after bladder-removal surgery. However, some people can't have or won't have this surgery. There is still a need for new treatments that let people keep their bladder. This is especially important for people who respond well to the enfortumab vedotin, when given with pembrolizumab, and may benefit from continuing this study treatment instead of having surgery.

The main aims of this study are to check how many people continue to respond well to enfortumab vedotin with pembrolizumab and how many people have their bladder intact after 2 years.

People in this study will be adults who have muscle-invasive bladder cancer and are able to have surgery to remove the bladder.

People cannot take part if they have nerve damage (sensory or motor neuropathy), have had certain other cancers, have diabetes that is not under control, or have had a transplant.

People will receive infusions of enfortumab vedotin on the 1st and 8th day of 3-week (21-day) cycles. They will also receive pembrolizumab on the 1st day of every 3-week cycle. There will be safety checks at each visit with checks of the tumors at some visits. The doctors will continue to check for medical problems throughout the study.

People will continue to receive study treatment unless their cancer doesn't improve after 9 cycles of study treatment, or until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly they pass away.

People's whose cancer gets worse or doesn't improve after 9 cycles may need bladder surgery, radiotherapy or chemotherapy. People will visit the clinic after they stop their study treatment, in which they will be asked about any medical problems and have a health check. After this, people will continue to have scans every 12 weeks (3 months) for the first 2 years until their cancer gets worse. After this, if their cancer doesn't get worse, they will continue to have scans every 24 weeks (6 months) for up to 5 years to check for any changes in their cancer. After people's cancer gets worse, they won't have any more scans but will have telephone health checks every 3 months.

Study Overview

• Status: Recruiting
• Conditions: Muscle-invasive Bladder Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Enfortumab Vedotin

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Astellas Pharma Global Development, Inc.; Phone Number: 800-888-7704; Email: Astellas.registration@astellas.com

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Recruiting
      • Arkansas Urology Associates
  • Illinois
    • Lisle, Illinois, United States, 60532
      • Recruiting
      • Accellacare of Duly
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Recruiting
      • Centers for Advanced Urology, LLP
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
    • Willow Grove, Pennsylvania, United States, 19090
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer - Asplundh Cancer Pavilion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has histologically-confirmed MIBC, stage cT2-T4aN0M0 or T1-T4aN1M0. NOTE: urothelial carcinomas (UCs) not originating from the bladder (e.g., upper tract [ureters, renal pelvis], urethra) are not eligible. UCs invading into the prostatic stroma with no histologic muscle invasion is allowed, provided that the extent of disease is confirmed via imaging.
• Participant has predominant UC histology (≥ 50%). NOTE: Participants with mixed histology are eligible provided the urothelial component is ≥ 50% (participants whose tumors contain predominant [≥ 50%] plasmacytoid variant are not eligible). Participants whose tumors contain any neuroendocrine histology are not eligible.
• Participant is deemed eligible for radical cystectomy and pelvic lymph node dissection.
• Participant has accessible archival tumor tissue from the primary tumor, for which source and availability have been confirmed prior to study intervention. If no archival tumor tissue is available, the participant will have a biopsy to obtain tumor tissue prior to study intervention.
• Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have a transurethral resection of a bladder tumor within 60 days (+14 days) prior to screening (from the date of informed consent form signature).

Exclusion Criteria:

• Participant has preexisting sensory or motor neuropathy Grade ≥ 2.
• Participant has ≥ N2 disease or metastatic disease (M1) as identified by imaging
• Participant has a history of uncontrolled diabetes mellitus within 3 months prior to screening. Uncontrolled diabetes (within 3 months before first dose) is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7% and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. The lowest HbA1c during the screening period will be used to determine eligibility.
• Participant has a second malignancy diagnosed within 3 years before first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. Participant with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
• Participant has known active keratitis or corneal ulcerations. Participant with superficial punctate keratitis is allowed if the disorder is being adequately treated.
• Participant has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
• Participant has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Participant 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 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.

• Participant has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

  • Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • Brief (< 7 days) use of systemic corticosteroids is allowed when use is considered standard of care.
  • Participant with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded.
  • Participant requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded.
  • Participant with hypothyroidism that is stable with hormone replacement therapy or Sjögren's syndrome will not be excluded.
• Participant has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed death-ligand 2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Participant has received prior systemic anti-cancer therapy for MIBC/non-muscle invasive bladder cancer (NMIBC), or received prior systemic anti-cancer therapy including investigational agents (including enfortumab vedotin or other monomethyl auristatin E-based antibody-drug conjugates) within 3 years prior to screening.

NOTE: Prior treatment for NMIBC with intravesical instillation therapy such as Bacillus Calmette-Guérin or intravesical chemotherapy is permitted. Prior systemic treatment (including, but not limited to, anti-PD-1/PD-L1 treatment with pembrolizumab, etc.) received for NMIBC is not permitted.

• Participant has received a partial cystectomy of the bladder to remove any NMIBC or MIBC.
• Participant has received any prior radiotherapy to the bladder.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enfortumab Vedotin with Pembrolizumab; Participants will receive enfortumab vedotin on days 1 and 8 of every 21-day cycle and pembrolizumab on day 1 of every 21-day cycle.	Drug: Pembrolizumab; IV; Drug: Enfortumab Vedotin; Intravenous infusion (IV); Other Names: ASG-22CE; PADCEV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall clinical complete response (cCR) rate after treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator	cCR rate is defined as the proportion of participants having cCR after treatment with enfortumab vedotin in combination with pembrolizumab. cRC is defined as no visible tumor detected on cystoscopy or no residual tumor on transurethral resection of bladder tumor (TURBT); no evidence of malignancy, except for the presence of Ta (low grade), and no radiographic evidence of residual or metastatic disease on imaging (magnetic resonance urogram [MRU] or computed tomography urogram [CTU] if contraindicated). Bladder wall thickening on imaging is acceptable if not associated with malignancy, except for the presence of Ta (low grade), and negative urine cytology.	Up to 27 weeks
Bladder-intact event-free survival (BI-EFS) rate in participants who achieve cRC after 9 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator	BI-EFS rate is defined as the proportion of participants who have not had an observed BI-EFS event 2 years after the first dose. BI-EFS is defined as the time from first dose to either histologically confirmed recurrent muscle-invasive bladder cancer (MIBC), disease progression, cystectomy, or death from any cause.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall cCR rate after 4 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator	cCR rate is defined as the proportion of participants having cCR after completing 4 cycles of enfortumab vedotin and/or pembrolizumab. cRC is defined as no visible tumor detected on cystoscopy or no residual tumor on TURBT; no evidence of malignancy, except for the presence of Ta (low grade), and no radiographic evidence of residual or metastatic disease on imaging (MRU or CTU if contraindicated). Bladder wall thickening on imaging is acceptable if not associated with malignancy, except for the presence of Ta (low grade), and negative urine cytology.	Up to 12 weeks
BI-EFS rate in participants who achieve cCR after 4 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator	BI-EFS rate is defined as the proportion of participants who have not had an observed BI-EFS event 2 years after the first dose. BI-EFS is defined as the time from first dose to either histologically confirmed recurrent MIBC, disease progression, cystectomy, or death from any cause.	2 years
Overall Survival (OS)	OS is defined as the time from first dose to death due to any cause in participants who achieve cCR after completing up to 9 cycles of enfortumab vedotin and/or pembrolizumab.	Up to 5 years
Disease-Free Survival (DFS) as assessed by investigator	DFS is defined as the time from cCR to the first occurrence of either radiologically or pathologically confirmed local or distant recurrence, or death from any cause in participants who achieve cCR after completing up to 9 cycles of enfortumab vedotin and/or pembrolizumab.	Up to 5 years
Metastatic-free Survival (MFS) as assessed by investigator	MFS is defined as the time from first dose to the first occurrence of either radiologically or pathologically confirmed distant metastasis, or death from any cause in participants who achieve cCR after completing up to 9 cycles of enfortumab vedotin and/or pembrolizumab.	Up to 5 years
Number of participants with Adverse Events (AEs)	AEs will be coded using the MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 12 months
Number of participants with laboratory value abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant laboratory values.	Up 11.5 months
Treatment discontinuation rate due to AEs	Treatment discontinuation rate is defined as the number of participants discontinuing due to AEs.	Up 12 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): April 30, 2031

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pembrolizumab; PADCEV; ASG-22CE; Enfortumab Vedotin; Bladder Preservation
• Additional Relevant MeSH Terms: pembrolizumab; enfortumab vedotin
• Other Study ID Numbers: 7465-CL-0209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No