Enfortumab Vedotin in Combination With Pembrolizumab vs. Concurrent Chemoradiotherapy (cCRT) in People With Muscle Invasive Bladder Cancer ( EV-309 )

Astellas

Status and phase: Enrolling; Phase 3

Conditions: Urinary Bladder Neoplasms; Urothelial Cancer

Treatments: Drug: Pembrolizumab; Radiation: Conventional Radiotherapy; Radiation: Hypofractionated Radiotherapy; Drug: Gemcitabine; Drug: Enfortumab vedotin; Drug: Mitomycin C; Drug: Fluorouracil; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT07566156

EV-309 (Other Identifier)

C5701009

2026-525612-34-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 390 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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)
• 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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390 participants in 2 patient groups

Arm A

Experimental group

Description:

Enfortumab vedotin + pembrolizumab (EV + P)

Treatment:

Drug: Enfortumab vedotin

Drug: Pembrolizumab

Arm B

Active Comparator group

Description:

Concurrent Chemoradiotherapy (cCRT)

Treatment:

Drug: Cisplatin

Drug: Mitomycin C

Drug: Fluorouracil

Drug: Gemcitabine

Radiation: Hypofractionated Radiotherapy

Radiation: Conventional Radiotherapy