By Fineline Cube 
Astellas (TSE: 4503) and Pfizer (NYSE: PFE) announced that their pivotal Phase III EV‑303 (KEYNOTE‑905) trial demonstrated a 60 % lower risk of event‑free survival (EFS) events in patients with muscle‑invasive bladder cancer (MIBC) who received neoadjuvant/adjuvant PADCEV (enfortumab vedotin) plus pembrolizumab versus surgery alone. The interim analysis, presented at the 2025 European Society for Medical Oncology (ESMO) Congress, also showed a 50 % reduction in death risk and a 79.7 % 2‑year overall survival (OS) rate in the combination arm.
Key Findings
- EFS Hazard Ratio (HR): 0.40 (95 % CI 0.28‑0.57; p < 0.0001)
- EFS Median: Not reached (combination) vs. 15.7 months (surgery)
- 2‑Year EFS: 74.7 % (combination) vs. 39.4 % (surgery)
- OS Hazard Ratio: 0.50 (95 % CI 0.33‑0.76; p < 0.0001)
- OS Median: Not reached (combination) vs. 41.7 months (surgery)
- 2‑Year OS: 79.7 % (combination) vs. 63.1 % (surgery)
Study Design
| Feature | PADCEV + Pembrolizumab (N = 210) | Surgery Alone (N = 210) |
|---|---|---|
| Treatment | 15 mg ER q.d. + 200 mg q.o.w. | Standard cystectomy ± adjuvant |
| Follow‑up | 24 months interim | 24 months interim |
| Primary Endpoint | EFS (tumor recurrence, progression, or death) | EFS |
| Secondary Endpoint | OS | OS |
Safety Profile
- Treatment‑emergent AEs: 84 % (combination) vs. 79 % (surgery) – mostly Grade 1‑2
- Grade ≥ 3 AEs: 23 % (combination) vs. 21 % (surgery) – manageable
- Infusion reactions: < 2 % (combination) – all Grade 1‑2
- No new safety signals identified relative to prior PADCEV and pembrolizumab data.
Implications for Bladder Cancer Therapy
- First‑in‑class ADC: Enfortumab vedotin targets Nectin‑4, a protein highly expressed in urothelial carcinoma.
- Expanded Indication: The data support PADCEV plus pembrolizumab as a neoadjuvant/adjuvant strategy for cisplatin‑ineligible MIBC patients.
- Regulatory Impact: Findings may inform FDA and EMA review for an expanded indication and could accelerate market access in key regions.
Forward‑Looking Statements
This release contains forward‑looking statements that involve risks and uncertainties. Actual results may differ materially.-Fineline Info & Tech