Pfizer and Astellas Pharma Report Positive Trial Results for Bladder-Cancer Treatment

Pfizer and Astellas Pharma reported positive Phase 3 trial results for their bladder-cancer treatment combination, demonstrating a significant improvement in event-free and overall survival compared to surgery alone. The drug combination is the first to improve survival in patients ineligible for cisplatin-based chemotherapy. The trial will continue to evaluate endpoints, and results will be discussed with global health authorities for potential regulatory filings.

Pfizer Inc. and Astellas Pharma Inc. announced significant results from the Phase 3 EV-303 clinical trial, which evaluated the combination of PADCEV (enfortumab vedotin) and KEYTRUDA (pembrolizumab) as neoadjuvant and adjuvant treatment for muscle-invasive bladder cancer (MIBC) patients ineligible for cisplatin-based chemotherapy. The study demonstrated a clinically meaningful and statistically significant improvement in event-free survival (EFS) and overall survival (OS) compared to surgery alone.

The EV-303 trial, also known as KEYNOTE-905, is an ongoing, open-label, randomized, three-arm, controlled, Phase 3 study that compared neoadjuvant and adjuvant KEYTRUDA (arm A), surgery alone (arm B), and neoadjuvant and adjuvant PADCEV in combination with KEYTRUDA (arm C) in MIBC patients not eligible for or declined cisplatin-based chemotherapy. The primary endpoint of the trial is EFS between arm C and arm B, defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy (RC) surgery, failure to undergo RC surgery in participants with residual disease, local or distant recurrence as assessed by imaging and/or biopsy, or death due to any cause.

At the first interim efficacy analysis, the trial showed a significant improvement in EFS and OS with neoadjuvant and adjuvant PADCEV plus KEYTRUDA versus surgery alone. An additional secondary endpoint of pathologic complete response (pCR) rate was also met. The safety profiles for PADCEV plus KEYTRUDA and KEYTRUDA monotherapy were consistent with the known profiles of each treatment regimen.

Christof Vulsteke, M.D., Ph.D., Head of Integrated Cancer Center Ghent (IKG, Belgium) and Clinical Trial Unit Oncology Ghent and EV-303 principal investigator, stated, "Patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy have not seen a significant treatment advance beyond surgery and face high rates of disease recurrence and a poor prognosis, even after having their bladder removed. These EV-303 study results mark the first time a systemic treatment approach, used before and after surgery, significantly extended survival over standard-of-care surgery in this population, demonstrating the potential of this combination to address a critical unmet patient need."

Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Head of Oncology Development, Astellas, noted, "These results from EV-303 represent a breakthrough for cisplatin-ineligible patients with muscle-invasive bladder cancer, demonstrating the potential of PADCEV in combination with KEYTRUDA when used before and after surgery as a new standard of care. We look forward to presenting further details on these data at an upcoming medical congress."

Johanna Bendell, M.D., Oncology Chief Development Officer, Pfizer, added, "PADCEV plus KEYTRUDA has already changed the treatment paradigm for patients with locally advanced or metastatic urothelial cancer as standard of care. These latest results underscore the practice-changing potential of this combination in earlier stages of bladder cancer, where it has the potential to improve outcomes for even more patients. Thank you to the patients and investigators who participated in this trial."

The trial will continue to evaluate the secondary EFS, OS, and pCR rate endpoints for neoadjuvant and adjuvant KEYTRUDA versus surgery alone as they continue to mature. Results will be submitted for presentation at an upcoming medical congress and will be discussed with global health authorities for potential regulatory filings. Neoadjuvant and adjuvant PADCEV plus KEYTRUDA is also being evaluated in cisplatin-eligible patients with MIBC in the EV-304 Phase 3 clinical trial (also known as KEYNOTE-B15).

References:
[1] https://www.astellas.com/en/news/29976