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.
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
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
Parallel
Enfortumab vedotin
DrugEnfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle up to cycle 9.
Conventional Radiotherapy
Radiation64 Gy in 32 fractions over 6.5 weeks administered to the participant's bladder only or the bladder and prophylactically to pelvic nodes.
Hypofractionated Radiotherapy
Radiation55 Gy in 20 fractions over 4 weeks administered to the participant's bladder only.
Cisplatin
Drug40 mg of cisplatin per meter squared of body surface area, administered once weekly via IV infusion during radiation OR 20 mg of cisplatin per meter squared of body surface area per day on Days 1 and 2 weekly via IV infusion during radiation.
Fluorouracil
Drug500 mg per meter squared of body surface area per day on Days 1-5 (week 1) and Days 22 26 (week 3) administered as continuous IV infusion during radiation in combination with mitomycin C.
Mitomycin C
Drug12 mg per meter squared of body surface area administered as an IV bolus on Day 1 during radiation in combination with fluorouracil.
Gemcitabine
Drug100 mg per meter squared of body surface area administered once weekly via IV infusion during radiation OR 27 mg per meter squared of body surface area administered twice weekly via IV infusion during radiation
Pembrolizumab
DrugIV infusion on Day 1 of every 3-week cycle up to cycle 17.
Bladder-intact Event Free Survival (BI-EFS) by Blinded Independent Central Review (BICR)
BI-EFS is defined as the time from randomization to any of the following events: histologically confirmed persistent or residual MIBC post-treatment confirmed by BICR, histologically confirmed recurrent MIBC by BICR, disease progression by BICR, cystectomy, or death from any cause.
Overall Survival (OS)
Time from randomization to death due to any cause.
Bladder-intact Event Free Survival (BI-EFS) by Investigator
BI-EFS is defined as the time from randomization to any of the following events: histologically confirmed persistent or residual MIBC post-treatment, histologically confirmed recurrent MIBC, disease progression, cystectomy, or death from any cause.
Complete clinical response (cCR) rate by Blinded Independent Central Review (BICR) and Investigator
cCR is defined as no radiographic evidence of residual or metastatic disease on imaging, negative cystoscopy, negative pathology except for low-grade Ta, and negative urine cytology.
Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR) and Investigator
Time from randomization to radiologically or pathologically confirmed distant metastasis, or death due to any cause, whichever occurs first.
Time to Cystectomy
The time from randomization to cystectomy.
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Astellas Pharma Global Development, Inc.
Lead sponsor
Pfizer
Collaborator