Informations générales (source: ClinicalTrials.gov)
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)
Interventional
Phase 2
Astellas Pharma Global Development, Inc. (Voir sur ClinicalTrials)
mars 2026
avril 2031
12 octobre 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Yohann LORIOT | 12/10/2026 13:55:05 | Contacter | ||
Critères
Tous
- 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).
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.