Urothelial CancerPhase 3NCT07566156
Enfortumab Vedotin in Combination With Pembrolizumab vs. Concurrent Chemoradiotherapy (cCRT) in People With Muscle Invasive Bladder Cancer (EV-309)
A Phase 3 study testing Enfortumab vedotin, Conventional Radiotherapy and Hypofractionated Radiotherapy in people with Urothelial Cancer and Urinary Bladder Neoplasms, run by Astellas Pharma Global Development, Inc. at 26 sites in 4 countries.
Trial summary
This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together as a bladder preservation approach to treat patients with muscle invasive bladder cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Cancer, Urinary Bladder Neoplasms
- What is being tested?
- Enfortumab vedotin, Conventional Radiotherapy and Hypofractionated Radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 390 participants
- Where
- 26 sitesin 4 countries
- Study dates
- 11 May 2026to 29 Feb 2032
- Phase
- Phase 3
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
- Has histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology staged cT2-T4aN0M0
- Tissue comprising muscle-invasive urothelial cancer must be submitted for clinical staging at baseline
- Eligible for and agree to receive chemoradiotherapy and one of the protocol-specified radiosensitizing chemotherapy regimens
- Fit for systemic therapy and elect bladder preservation, including participants who are ineligible for or have elected not to undergo cystectomy
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Who cannot join
- Advanced or metastatic disease (N+, M1), non-urothelial carcinoma, diffuse or multifocal CIS, urothelial carcinoma or histological variant at any site outside the urinary bladder within previous 24 months prior to randomization except Ta/T1/CIS of the upper urinary tract including renal pelvis and ureter if the participant had undergone complete nephrectomy
- Has received any prior systemic treatment, chemoradiation, and/or radiation for MIBC or NMIBC
- Prior pelvic radiation for any reason
- Inadequate bladder function
- Other active malignancies within 3 years prior to randomization
- Previously treated with enfortumab vedotin or other MMAE-based antibody-drug conjugates (ADCs)
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- Previously treated with a PD(L)-1 inhibitor, defined as a PD-1 inhibitor or PD-L1 inhibitor
- Uncontrolled diabetes
- Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted
- Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection
- Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization
- Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
- Known genetic disorders associated with radiosensitivity (eg, ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi syndrome)
- Active keratitis or corneal ulcerations
- History of autoimmune disease that has required systemic treatment in the past 2 years
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Prior allogeneic stem cell or solid organ transplant
- Received a live attenuated vaccine within 30 days prior to randomization
Trial locations and contacts
26 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
26 sites in 4 countries
United States19 sites, 19 recruiting
- Recruiting
Rocky Mountain Cancer Center
Aurora, Colorado, 80012
- Recruiting
Texas Oncology
Austin, Texas, 78705
- Recruiting
Missouri Cancer Associates
Columbia, Missouri, 65201
- Recruiting
Williamette Valley Cancer Institute and Research Center
Eugene, Oregon, 97401
- Recruiting
Oncology Hematology Care Clinical Trials, LLC
Fairfield, Ohio, 45014
- Recruiting
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, 46825
- Recruiting
Hope and Healing Clinical Research LLC
Hinsdale, Illinois, 60521
- Recruiting
Arkansas Urology
Little Rock, Arkansas, 72211
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
Hope and Healing Clinical Research LLC
New Lenox, Illinois, 60451
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
- Recruiting
Medical Oncology Hematology Consultants
Newark, Delaware, 19713
- Recruiting
Illinois Cancer Specialists
Niles, Illinois, 60714
- Recruiting
Virginia Oncology Associates
Norfolk, Virginia, 23502
- Recruiting
Comprehensive Urology
Royal Oak, Michigan, 48073
- Recruiting
Samsun Clinic - Ridley-Tree Cancer Center
Santa Barbara, California, 93105
- Recruiting
Siteman Cancer Center
St Louis, Missouri, 63110
- Recruiting
Compass Oncology - West
Tigard, Oregon, 97223
- Recruiting
Texas Oncology - Northeast Texas
Tyler, Texas, 75702
South Korea4 sites, 4 recruiting
- Recruiting
Site KR01113
Daegu
- Recruiting
Site KR01063
Seongnam-si
- Recruiting
Site KR01065
Seoul
- Recruiting
Site KR01084
Seoul
Canada2 sites, 2 recruiting
- Recruiting
Site CA01194
Chicoutimi, Quebec
- Recruiting
Site CA01071
Montreal, Quebec
About this study
Official title: A PHASE 3, OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE ENFORTUMAB VEDOTIN IN COMBINATION WITH PEMBROLIZUMAB IN ADULT PARTICIPANTS WITH MUSCLE-INVASIVE BLADDER CANCER WHO ARE INELIGIBLE FOR OR HAVE ELECTED NOT TO UNDERGO CYSTECTOMY
This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together as a bladder preservation approach to treat patients with muscle invasive bladder cancer. The study will compare these drugs to concurrent chemoradiotherapy that is usually used to treat this cancer (standard of care). The study will enroll patients with muscle-invasive bladder cancer (MIBC) who have cancer that has not spread outside the bladder.
Read the detailed description
This study is being conducted to evaluate the combination of enfortumab vedotin + pembrolizumab versus standard of care concurrent chemoradiotherapy, in subjects with previously untreated muscle invasive bladder cancer.
Enfortumab vedotin may be administered for up to 9 cycles or a protocol defined reason for study discontinuation occurs, whichever is first. Pembrolizumab may be administered for a maximum of 17 cycles (3-week cycles) or a protocol-defined reason for study discontinuation occurs, whichever is first. Concurrent chemoradiotherapy may be administered for a maximum of 6.5 weeks.
- Conditions
- Urothelial Cancer, Urinary Bladder Neoplasms
- Being tested
- Enfortumab vedotin, Conventional Radiotherapy, Hypofractionated Radiotherapy, Cisplatin, Fluorouracil
- Keywords
- Urologic Neoplasms, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy, Complications, Urogenital Diseases, Urinary Bladder Diseases, Urologic Diseases, Male Urogenital Diseases, Urinary Bladder Neoplasms, Cisplatin, Fluorouracil, Mitomycin, Gemcitabine, Muscle Invasive Bladder Cancer, Enfortumab vedotin, Pembrolizumab, Urothelial Cancer
- Medical subject headings
- Urinary Bladder Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Female Urogenital Diseases, Urogenital Diseases, Urinary Bladder Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enfortumab vedotinDrug
Also called • Padcev, • ASG-22CE, • ASG-22Me
Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle up to cycle 9.
Conventional RadiotherapyRadiation
64 Gy in 32 fractions over 6.5 weeks administered to the participant's bladder only or the bladder and prophylactically to pelvic nodes.
Hypofractionated RadiotherapyRadiation
55 Gy in 20 fractions over 4 weeks administered to the participant's bladder only.
CisplatinDrug
40 mg of cisplatin per meter squared of body surface area, administered once weekly via IV infusion during radiation OR 20 mg of cisplatin per meter squared of body surface area per day on Days 1 and 2 weekly via IV infusion during radiation.
FluorouracilDrug
Also called • 5-Fluorouracil, • 5-FU
500 mg per meter squared of body surface area per day on Days 1-5 (week 1) and Days 22 26 (week 3) administered as continuous IV infusion during radiation in combination with mitomycin C.
Mitomycin CDrug
Also called • MMC
12 mg per meter squared of body surface area administered as an IV bolus on Day 1 during radiation in combination with fluorouracil.
GemcitabineDrug
100 mg per meter squared of body surface area administered once weekly via IV infusion during radiation OR 27 mg per meter squared of body surface area administered twice weekly via IV infusion during radiation
PembrolizumabDrug
Also called Keytruda
IV infusion on Day 1 of every 3-week cycle up to cycle 17.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Enfortumab vedotin + pembrolizumab (EV + P) Receives: Drug: Enfortumab vedotin; Drug: Pembrolizumab |
| Arm B | Active comparator | Concurrent Chemoradiotherapy (cCRT) Receives: Radiation: Conventional Radiotherapy; Radiation: Hypofractionated Radiotherapy; Drug: Cisplatin; Drug: Fluorouracil; Drug: Mitomycin C; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bladder-intact Event Free Survival (BI-EFS) by Blinded Independent Central Review (BICR)
BI-EFS is defined as the time from randomization to any of the following events: histologically confirmed persistent or residual MIBC post-treatment confirmed by BICR, histologically confirmed recurrent MIBC by BICR, disease progression by BICR, cystectomy, or death from any cause.
Measured: Up to approximately 45.5 months
Overall Survival (OS)
Time from randomization to death due to any cause.
Measured: Up to approximately 60 months
Secondary outcomes (8)
Bladder-intact Event Free Survival (BI-EFS) by Investigator
BI-EFS is defined as the time from randomization to any of the following events: histologically confirmed persistent or residual MIBC post-treatment, histologically confirmed recurrent MIBC, disease progression, cystectomy, or death from any cause.
Measured: Up to approximately 45.5 months
Complete clinical response (cCR) rate by Blinded Independent Central Review (BICR) and Investigator
cCR is defined as no radiographic evidence of residual or metastatic disease on imaging, negative cystoscopy, negative pathology except for low-grade Ta, and negative urine cytology.
Measured: Up to approximately 60 months
Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR) and Investigator
Time from randomization to radiologically or pathologically confirmed distant metastasis, or death due to any cause, whichever occurs first.
Measured: Up to approximately 60 months]
Time to Cystectomy
The time from randomization to cystectomy.
Measured: Up to approximately 60 months
Disease Free Survival (DFS) by Blinded Independent Central Review (BICR) and Investigator
The time from cCR to local recurrence or distant metastases, a second primary bladder cancer, or death due to any cause, whichever occurs first.
Measured: Up to approximately 60 months
Cystectomy Free Survival (CFS)
The time from randomization to cystectomy or death due to any cause, whichever occurs first.
Measured: Up to approximately 60 months
Number of Participants with Treatment Emergent Adverse Event (TEAE)
An AE is any untoward medical occurrence in a participant who receives a study treatment without regard to possibility of causal relationship. Treatment-emergent are events between the first dose of study treatment and up to 30 days after the last dose that were absent before treatment or that worsened relative to pretreatment state.
Measured: From start of study treatment up to 30 days after last dose of study drug (approximately up to 1.1 years)
Number of Participants with Serious TEAEs
An SAE is any AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 90 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measured: From start of treatment up to 90 days after the last dose of study treatment (approximately up to 1.3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2026
- Study start11 May 2026
- Primary completion31 Mar 2030 (estimated)
- Study completion29 Feb 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CancerStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized, controlled, parallel-group, multicenter, open-label study of EV in combination with pembrolizumab versus an active comparator-cCRT in adult participants with MIBC who are ineligible for or have elected not to undergo cystectomy. The study is open-label, and the investigators, participants, and sponsor will be aware of the study intervention assignment. The study intervention assignment is by randomization (1:1).
- Masking
- None (open label)
- Enrolment
- 390 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Zejing Wang, MD/PhD, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07566156
- Sponsor's protocol ID
- C5701009
- Other IDs
- EV-309, 2026-525612-34-00
- Status last verified
- Oct 2026
- First submitted
- 29 Apr 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.