Astellas/Pfizer’s Padcev plus Keytruda hits endpoints in latest Phase 3 for early-stage bladder cancer

Astellas Pharma Inc., and Pfizer Inc., unveiled positive topline results from a Phase 3 trial assessing the perioperative combination of Padcev (enfortumab vedotin-ejfv) and Keytruda (pembrolizumab) in patients with muscle-invasive bladder cancer (MIBC). The regimen significantly improved survival outcomes in cisplatin-eligible patients when given before and after surgery, and adds to a previous positive Phase 3 readout for Padcev in cisplatin-ineligible patients.

The Phase III EV-304 (also known as KEYNOTE-B15) clinical trial evaluated Padcev plus Keytruda as a neoadjuvant and adjuvant regimen in cisplatin-eligible MIBC patients, meeting the primary endpoint of event-free survival (EFS) and key secondary endpoints, including overall survival (OS) and pathologic complete response (pCR) rate.

Key findings from the trial

• The Padcev + Keytruda combination significantly extended EFS and OS compared with the current standard of care.
• Risk of death was reduced by 50% versus surgery alone, with median OS not reached in the combination arm versus an observed median in the control arm.
• Pathologic complete response rates were markedly higher with the combination, indicating deeper tumour eradication at surgery.

This regimen is the first immunotherapy plus antibody-drug conjugate (ADC) combination to demonstrate durable survival benefit when administered both before and after surgery in cisplatin-eligible MIBC patients.

The results bolster earlier evidence from the EV-303 (KEYNOTE-905) trial in cisplatin-ineligible or cisplatin-declining patients with MIBC, where Padcev plus Keytruda significantly reduced the risk of recurrence, progression, or death and improved survival outcomes versus surgery alone.

Key takeaways

The findings could support regulatory submissions for perioperative Padcev plus Keytruda in earlier stages of bladder cancer and potentially redefine standard of care across cisplatin eligibility subgroups, addressing a key unmet need in MIBC treatment.

Muscle-invasive bladder cancer is an aggressive form of bladder cancer in which tumour cells have penetrated the muscle layer of the bladder wall. The current standard of care in the perioperative setting typically involves neoadjuvant chemotherapy followed by radical cystectomy with pelvic lymph node dissection. Cisplatin-based combination regimens (such as gemcitabine/cisplatin or MVAC: methotrexate, vinblastine, doxorubicin, cisplatin) are most commonly used as first-line NAC for eligible patients.