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

NCT07566156 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: C5701009EV-3092026-525612-34-00
• Study Type: interventional
• Target: 390
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Urothelial Cancer; Urinary Bladder Neoplasms

Keywords

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy; Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Cisplatin; Fluorouracil; Mitomycin; Gemcitabine; Muscle Invasive Bladder Cancer; Enfortumab vedotin; Pembrolizumab; Urothelial Cancer; Urothelial Carcinoma; Bladder-sparing; Bladder Preservation

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to approximately 45.5 months

• Overall Survival (OS)

  Time from randomization to death due to any cause.

  Up to approximately 60 months

Secondary Outcomes (8)

• Bladder-intact Event Free Survival (BI-EFS) by Investigator

  Up to approximately 45.5 months

• Complete clinical response (cCR) rate by Blinded Independent Central Review (BICR) and Investigator

  Up to approximately 60 months

• Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR) and Investigator

  Up to approximately 60 months]

• Time to Cystectomy

  Up to approximately 60 months

• Disease Free Survival (DFS) by Blinded Independent Central Review (BICR) and Investigator

  Up to approximately 60 months

Study Arms (2)

Arm A

EXPERIMENTAL

Enfortumab vedotin + pembrolizumab (EV + P)

Drug: Enfortumab vedotin; Drug: Pembrolizumab

Arm B

ACTIVE COMPARATOR

Concurrent Chemoradiotherapy (cCRT)

Radiation: Conventional Radiotherapy; Radiation: Hypofractionated Radiotherapy; Drug: Cisplatin; Drug: Fluorouracil; Drug: Mitomycin C; Drug: Gemcitabine

Interventions

Enfortumab vedotin DRUG

Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle up to cycle 9.

Also known as: • Padcev, • ASG-22CE, • ASG-22Me

Arm A

Conventional Radiotherapy RADIATION

64 Gy in 32 fractions over 6.5 weeks administered to the participant's bladder only or the bladder and prophylactically to pelvic nodes.

Arm B

Hypofractionated Radiotherapy RADIATION

55 Gy in 20 fractions over 4 weeks administered to the participant's bladder only.

Arm B

Cisplatin DRUG

40 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.

Arm B

Fluorouracil DRUG

500 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.

Also known as: • 5-Fluorouracil, • 5-FU

Arm B

Mitomycin C DRUG

12 mg per meter squared of body surface area administered as an IV bolus on Day 1 during radiation in combination with fluorouracil.

Also known as: • MMC

Arm B

Gemcitabine DRUG

100 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

Arm B

Pembrolizumab DRUG

IV infusion on Day 1 of every 3-week cycle up to cycle 17.

Also known as: Keytruda

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 syndrom, Fanconi syndrome)
• Active keratitis or corneal ulcerations
• History of autoimmune disease that has required systemic treatment in the past 2 years

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Pfizer: collaborator

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Transitional Cell

Interventions

enfortumab vedotin; Radiation Dose Hypofractionation; Cisplatin; Fluorouracil; Mitomycin; Gemcitabine; pembrolizumab

Condition Hierarchy (Ancestors)

Female Urogenital Diseases and Pregnancy Complications; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides

Study Officials

• Zejing Wang, MD/PhD

  Pfizer

  STUDY DIRECTOR

Central Study Contacts

Pfizer CT.gov Call Center

CONTACT

1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A randomized, controlled, parallel-group, multicenter, open-label study of EV in combination with pembrolizumab versus an active comparator-cCRT in adult participants with MIBC who are ineligible for or have elected not to undergo cystectomy. The study is open-label, and the investigators, participants, and sponsor will be aware of the study intervention assignment. The study intervention assignment is by randomization (1:1).

Study Record Dates

• First Submitted: April 29, 2026
• First Posted: May 4, 2026
• Study Start (Estimated): May 11, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): February 29, 2032
• Last Updated: May 4, 2026

Record last verified: 2026-04