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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)

A study to find out if enfortumab vedotin given with pembrolizumab helps people with muscle-invasive bladder cancer keep their bladder

Blanca Trujillo

Astellas Pharma Inc.

2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo

clinicaltrialregistration@astellas.com

Medical Information Center

Astellas Pharma Inc.

2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo

+81-120-189-371

clinicaltrialregistration@astellas.com

Recruiting

June. 23, 2026

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Participant has histologically-confirmed muscle-invasive bladder cancer (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.
2. 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.
3. Participant is deemed eligible for radical cystectomy (RC) and pelvic lymph node dissection (PLND).
4. 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.
5. Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
6. Have a transurethral resection (TUR) of a bladder tumor within 60 days (+14 days) prior to, or during, screening (from the date of ICF signature).

1. Participant has preexisting sensory or motor neuropathy Grade >/= 2.
2. Participant has >/= N2 disease or metastatic disease (M1) as identified by imaging
3. 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.
4. 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.
5. Participant has known active keratitis or corneal ulcerations. Participant with superficial punctate keratitis is allowed if the disorder is being adequately treated.
6. Participant has a history of (non-infectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
7. 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.
8. 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.
9. 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).
a) 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.
b) Brief (< 7 days) use of systemic corticosteroids is allowed when use is considered standard of care.
c) Participant with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded.
d) Participant requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded.
e) Participant with hypothyroidism that is stable with hormone replacement therapy or Sjogren's syndrome will not be excluded.
10. 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 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic t-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137).
11. 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 [MMAE]-based antibody-drug conjugates within 3 years prior to screening.
NOTE: Prior treatment for NMIBC with intravesical instillation therapy such as Bacillus Calmette-Guerin 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.
12. Participant has received a partial cystectomy of the bladder to remove any NMIBC or MIBC.
13. Participant has received any prior radiotherapy to the bladder.

Both

Muscle-invasive Bladder Cancer

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.

- Overall clinical complete response (cCR) rate after treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator
- 2-year bladder-intact event-free survival (BI-EFS) rate in participants who achieve cCR after completing up to 9 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator

- Overall cCR rate after 4 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator
- 2-year BI-EFS rate in participants who achieve cCR after 4 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator
- Overall survival (OS) in participants who achieve cCR after completing up to 9 cycles of treatment with enfortumab vedotin in combination with pembrolizumab
- Disease-free survival (DFS) in participants who achieve cCR after completing up to 9 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator
- Metastatic-free survival (MFS) in participants who achieve cCR after completing up to 9 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator
- Type, incidence, relatedness, severity and seriousness of safety variables (AEs and laboratory tests)
- Treatment discontinuation rate due to AEs

+81-6-6645-3447

May. 28, 2026

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 products 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/. Study-related supporting documentation is redacted and provided if available, such as the protocol and amendments, statistical analysis plan and clinical study report. 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. 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.

United States/South Korea/Spain/Garmany