Positive results from phase III EV-303 clinical trial of Padcev (enfortumab vedotin) + Keytruda (pembrolizumab) as neoadjuvant /adjuvant treatment for MIBC-. Pfizer + Astellas

 Pfizer Inc.  and Astellas Pharma Inc.  announced positive topline results from the Phase IIII EV-303 clinical trial (also known as KEYNOTE-905). The EV-303 study is evaluating Padcev (enfortumab vedotin), a Nectin-4 directed antibody-drug conjugate, in combination with Keytruda (pembrolizumab), a PD-1 inhibitor, as neoadjuvant and adjuvant treatment (before and after surgery) versus surgery alone, the current standard of care, in patients with muscle-invasive bladder cancer (MIBC) who are not eligible for or declined cisplatin-based chemotherapy.

At the first interim efficacy analysis, the trial demonstrated a clinically meaningful and statistically significant improvement in event-free survival (EFS), the study’s primary endpoint, and overall survival (OS), a key secondary endpoint, with neoadjuvant and adjuvant  Padcev  plus Keytruda  versus surgery alone. An additional secondary endpoint of pathologic complete response (pCR) rate was also met.

The trial is continuing to evaluate the secondary EFS, OS and pCR rate endpoints for neoadjuvant and adjuvant Keytruda versus surgery alone as they continue to mature. The safety profiles for  Padcev plus Keytruda and Keytruda monotherapy were consistent with the known profiles of each treatment regimen.

The EV-303 Trial (NCT03924895) is an ongoing, open-label, randomized, three-arm, controlled, Phase III study evaluating neoadjuvant and adjuvant Padcev  in combination with Keytruda  or neoadjuvant and adjuvant Keytruda  versus surgery alone in patients with MIBC who are either not eligible for or declined cisplatin-based chemotherapy. Patients were randomized to receive either neoadjuvant and adjuvant Keytruda  (arm A), surgery alone (arm B) or neoadjuvant and adjuvant Padcev in combination with Keytruda (arm C).

The primary endpoint of this trial is EFS between arm C versus 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 or failure to undergo RC surgery in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy or death due to any cause. Key secondary endpoints include OS and pCR rate between arm C and arm B, as well as EFS, OS and pCR rate between arm A and arm B

The trial is continuing to evaluate the secondary EFS, OS and pCR rate endpoints for neoadjuvant and adjuvant Keytruda versus surgery alone as they continue to mature. The safety profiles for PADCEV plus Keytruda and Keytruda monotherapy were consistent with the known profiles of each treatment regimen.

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 III clinical trial (also known as KEYNOTE-B15).

About the EV-303 Trial ; The EV-303 trial is an ongoing, open-label, randomized, three-arm, controlled, Phase III study evaluating neoadjuvant and adjuvant PADCEV in combination with Keytruda or neoadjuvant and adjuvant Keytruda  versus surgery alone in patients with MIBC who are either not eligible for or declined cisplatin-based chemotherapy. Patients were randomized to receive either neoadjuvant and adjuvant Keytruda (arm A), surgery alone (arm B) or neoadjuvant and adjuvant PADCEV in combination with Keytruda (arm C).

The primary endpoint of this trial is EFS between arm C versus 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 or failure to undergo RC surgery in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy or death due to any cause. Key secondary endpoints include OS and pCR rate between arm C and arm B, as well as EFS, OS and pCR rate between arm A and arm B.

Seagen and Astellas previously entered a clinical collaboration agreement with Merck to evaluate the combination of Seagen’s and Astellas’ PADCEV (enfortumab vedotin) and Merck’s Keytruda (pembrolizumab) in patients with muscle-invasive bladder cancer (MIBC) who are not eligible for or declined cisplatin-based chemotherapy. Pfizer Inc. successfully completed its acquisition of Seagen on December 14, 2023. Keytruda is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada