Keytruda (pembrolizumab) plus Padcev (enfortumab vedotin-ejfv) demonstrated statistically significant and clinically meaningful improvements in event-free survival, overall survival, and pathologic complete response rates in the perioperative setting for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy in the Phase 3 KEYNOTE-905/EV-303 trial. This represents the first and only systemic therapy to improve survival when used before and after surgery in this high-risk, cisplatin-ineligible population, marking a significant advancement in MIBC treatment where no progress has been made beyond surgery alone.
Key Trial Design & Population:
- KEYNOTE-905/EV-303 Phase 3, open-label, randomized, multi-arm trial
- 595 patients with cT2-T4aN0-N1M0 cisplatin-ineligible MIBC eligible for radical cystectomy
- Three arms: (A) neoadjuvant Keytruda → surgery → adjuvant Keytruda; (B) surgery alone; (C) neoadjuvant Keytruda + Padcev → surgery → adjuvant Keytruda + Padcev then Keytruda alone
- Primary endpoint: event-free survival (EFS) comparing Arm C vs. Arm B
- Key secondary endpoints: overall survival (OS) and pathologic complete response (pCR) rate
Key Findings:
- Statistically significant improvement in EFS (primary endpoint) for Keytruda + Padcev vs. surgery alone
- Statistically significant improvement in OS compared to surgery alone
- Statistically significant improvement in pCR rate with combination therapy
- First-ever positive Phase 3 study in cisplatin-ineligible MIBC population
- Safety profile consistent with known profiles of Keytruda and Padcev; no new safety signals identified
Clinical Implications:
- Addresses critical unmet need for approximately 50% of MIBC patients who cannot receive cisplatin-based chemotherapy
- First systemic treatment to demonstrate survival benefit in perioperative setting for this population
- Potential new standard of care for cisplatin-ineligible MIBC patients
- Builds on existing approval of Keytruda + Padcev for locally advanced/metastatic urothelial cancer
- Significantly advances treatment paradigm beyond surgery alone, which has been the only option for this population
Development Status & Next Steps:
- Full trial results to be presented at upcoming medical meeting
- Regulatory submissions planned to FDA and global authorities
- Trial continuing to evaluate secondary endpoints comparing neoadjuvant/adjuvant Keytruda alone (Arm A) vs. surgery alone (Arm B)
- Part of broader development program: 5 additional Phase 3 studies evaluating Keytruda across all bladder cancer stages
- Conducted in collaboration with Pfizer (previously Seagen) and Astellas
