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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Bladder-intact Event Free Survival (BI-EFS) by Blinded Independent Central Review (BICR)

Primary Outcome 1 - Timeframe: Up to approximately 45.5 months

Primary Outcome 2 - Measure: Overall Survival (OS)

Primary Outcome 2 - Timeframe: Up to approximately 60 months

CONDITION

• Urothelial Cancer
• Urinary Bladder Neoplasms

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Zejing Wang, MD/PhD

Role: Study Director

Affiliation: Pfizer

Overall Contact

Name: Pfizer CT.gov Call Center

Phone: 1-800-718-1021

Email: [email protected]

LOCATION