Muscle-invasive Bladder CancerPhase 2NCT07475806
A Study to Find Out if Enfortumab Vedotin Given With Pembrolizumab Helps People With Muscle-invasive Bladder Cancer Keep Their Bladder
A Phase 2 study testing Enfortumab Vedotin and Pembrolizumab in people with Muscle-invasive Bladder Cancer, run by Astellas Pharma Global Development, Inc. at 66 sites in 12 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Muscle-invasive Bladder Cancer
- 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
- 240 participants
- Where
- 66 sitesin 12 countries
- Study dates
- 12 Mar 2026to 30 Apr 2031
- Phase
- Phase 2
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
- 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, or during screening (from the date of informed consent form signature).
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
66 sites in 12 countries. Contact the study team or a site near you to ask about taking part.
66 sites in 12 countries
United States19 sites, 19 recruiting
- Recruiting
Centers for Advanced Urology, LLP
Bala-Cynwyd, Pennsylvania, 19004
- Recruiting
Sidney Kimmel Comprehensive Cancer Center (SKCCC) Cherry Hill
Cherry Hill, New Jersey, 08002
- Recruiting
University of Illinois College of Medicine - UIC Cancer Center
Chicago, Illinois, 60612
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Indiana University School of Medicine - Simon Cancer Center
Indianapolis, Indiana, 46202
- Recruiting
Accellacare of Duly
Lisle, Illinois, 60532
- Recruiting
Arkansas Urology Associates
Little Rock, Arkansas, 72211
- Recruiting
University of Wisconsin Hospitals and Clinics
Madison, Wisconsin, 53792
- Recruiting
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
- Recruiting
NYU Langone Urology Associates
New York, New York, 10017
- Recruiting
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
- Recruiting
Urology Austin, PLLC
Round Rock, Texas, 78681
- Recruiting
Profound Research LLC at Michigan Hematology and Oncology Consultants
Royal Oak, Michigan, 48073
- Recruiting
Urology San Antonio
San Antonio, Texas, 78229
- Recruiting
Stanford University School of Medicine
Stanford, California, 94305
- Recruiting
Sidney Kimmel Comprehensive Cancer Center (SKCC) Washington Township
Washington Township, New Jersey, 08080
- Recruiting
The University of Kansas Cancer Center
Westwood, Kansas, 66205
- Recruiting
Sidney Kimmel Comprehensive Cancer - Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
Japan10 sites, 10 recruiting
- Recruiting
Institute of Science Tokyo Hospital
Bunkyo-ku, Tokyo
- Recruiting
Tokyo Metropolitan Hospital Organization-Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Bunkyo-ku, Tokyo
- Recruiting
Gifu University Hospital
Gifu, Gifu
- Recruiting
St. Marianna University Hospital
Kawasaki, Kanagawa
- Recruiting
Kobe City Hospital Organization - Kobe City Medical Center General Hospital
Kobe, Hyōgo
- Recruiting
The Cancer Institute Hospital-Japanese Foundation for Cancer
Koto-ku, Tokyo
- Recruiting
Kyoto University Hospital
Kyoto
- Recruiting
Osaka Metropolitan University Hospital
Osaka
- Recruiting
University of Tsukuba Hospital
Tsukuba, Ibaraki
- Recruiting
Yamaguchi University Hospital - Center For Clinical Research
Ube, Yamaguchi
France8 sites, 8 recruiting
- Recruiting
Site FR33004
Cedex Lyon 08
- Recruiting
Site FR33002
Paris
- Recruiting
Site FR33013
Rennes
- Recruiting
Site FR33009
Strasbourg
- Recruiting
Site FR33012
Strasbourg
- Recruiting
Site FR33011
Suresnes
- Recruiting
Site FR33003
Toulouse
- Recruiting
Site FR33010
Villejuif
South Korea8 sites, 8 recruiting
- Recruiting
Site KR82007
Gyeonggi-do
- Recruiting
Site KR82004
Hwasun, Jeollanam-do
- Recruiting
Site KR82002
Seongnam-si, Gyeonggi-do
- Recruiting
Site KR82001
Seoul
- Recruiting
Site KR82003
Seoul
- Recruiting
Site KR82005
Seoul
- Recruiting
Site KR82008
Seoul
- Recruiting
Site KR82010
Seoul
Italy4 sites, 4 recruiting
- Recruiting
Site IT39013
Bari
- Recruiting
Site IT39005
Foggia
- Recruiting
Site IT39009
Meldola
- Recruiting
Site IT39017
Milan
Poland4 sites, 4 recruiting
- Recruiting
Site PL48005
Lodz
- Recruiting
Site PL48007
Opole
- Recruiting
Site PL48008
Poznan
- Recruiting
Site PL48006
Przemyśl
United Kingdom4 sites, 4 recruiting
- Recruiting
Site UK44003
Colchester
- Recruiting
Site GB44005
London
- Recruiting
Site UK44004
London
- Recruiting
Site UK44001
Plymouth
Spain3 sites, 3 recruiting
- Recruiting
Site ES34011
Granada
- Recruiting
Site ES34002
Ourense
- Recruiting
Site ES34005
Pamplona
Australia2 sites, 2 recruiting
- Recruiting
Site AU61002
New South Wales
- Recruiting
Site AU61005
Southport, Queensland
China2 sites, 2 recruiting
- Recruiting
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing
- Recruiting
Langfang Campus, Cancer Hospital Chinese Academy of Medical Science
Langfang
About this study
Official title: 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.
Read more
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.
- Conditions
- Muscle-invasive Bladder Cancer
- Being tested
- Enfortumab Vedotin, Pembrolizumab
- Keywords
- ASG-22CE, Enfortumab Vedotin, Bladder Preservation, Pembrolizumab, PADCEV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enfortumab VedotinDrug
Also called ASG-22CE, PADCEV
Intravenous infusion (IV)
PembrolizumabDrug
IV
| Study group | Role | What they receive |
|---|---|---|
| Enfortumab Vedotin with Pembrolizumab | Experimental | 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. Receives: Drug: Enfortumab Vedotin; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
cCR 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.
Measured: 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.
Measured: 2 years
Secondary outcomes (8)
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.
cCR 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up 11.5 months
Treatment discontinuation rate due to AEs
Treatment discontinuation rate is defined as the number of participants discontinuing due to AEs.
Measured: Up 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2026
- Study start12 Mar 2026
- Primary completion30 Nov 2027 (estimated)
- Study completion30 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle-invasive Bladder 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07475806
- Sponsor's protocol ID
- 7465-CL-0209
- Status last verified
- Oct 2026
- First submitted
- 13 Mar 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/.