PADCEV™ (enfortumab vedotin) plus KEYTRUDA™ (pembrolizumab) significantly improves survival for certain patients with bladder cancer when given before and after surgery

• Enfortumab vedotin plus pembrolizumab is the first and only regimen to improve survival when used before and after standard of care (surgical cystectomy) in cisplatin-ineligible patients with muscle-invasive bladder cancer

• Results will be discussed with global health authorities for potential regulatory filings

Astellas Pharma recently announced positive topline results from the Phase 3 EV-303 clinical trial (also known as KEYNOTE-905). The EV-303 study is evaluating PADCEV^TM (enfortumab vedotin), a Nectin-4 directed antibody-drug conjugate, in combination with KEYTRUDA^TM (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 enfortumab vedotin plus pembrolizumab 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 pembrolizumab versus surgery alone as they continue to mature. The safety profiles for enfortumab vedotin plus pembrolizumab and pembrolizumab monotherapy were consistent with the known profiles of each treatment regimen.

Bladder cancer is the ninth most common cancer worldwide, diagnosed in more than 614,000 patients each year globally.[i] MIBC represents approximately 30% of all bladder cancer cases.[ii] The standard treatment for patients with MIBC is neoadjuvant cisplatin-based chemotherapy followed by surgery, which has been shown to prolong survival.ⁱⁱHowever, up to half of patients with MIBC are not eligible to receive cisplatin and face limited treatment options, typically undergoing surgery alone.[iii]

”There is a high unmet need for systemic treatments in patients not eligible for cisplatin and the results seen in EV-303 appears very encouraging for this group of patients”, says Elinor Cockburn, Head of Medical Affairs in Astellas Nordic.

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 enfortumab vedotin plus pembrolizumab is also being evaluated in cisplatin-eligible patients with MIBC in the EV-304 Phase 3 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 3 study evaluating neoadjuvant and adjuvant enfortumab vedotin in combination with pembrolizumab or neoadjuvant and adjuvant pembrolizumab 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 pembrolizumab (arm A), surgery alone (arm B) or neoadjuvant and adjuvant enfortumab vedotin in combination with pembrolizumab (arm C).[iv] Several Nordic sites are participating in this clinical trial.

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.^iv

For more information on the global EV-303 trial, go to clinicaltrials.gov.

About PADCEV^TM (enfortumab vedotin)
Enfortumab vedotin is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.[v] Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).[vi]

Enfortumab vedotin plus pembrolizumab is approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) regardless of cisplatin eligibility in the United States, the European Union, Japan and a number of other countries around the world. Enfortumab vedotin is also approved as a single agent for the treatment of adult patients with la/mUC who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.^vi

About Astellas

Astellas Pharma is a company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. We focus on Urology, Oncology and Women’s health prioritized therapeutic areas. Astellas vision is to be on the forefront of healthcare change by turning innovative science into value for patients. With our Nordic office in Copenhagen Astellas is represented in the whole Nordic region.

For more information:

Elinor Cockburn, Medical Affairs, Astellas Pharma, elinor.cockburn@astellas.com, +45 4343 0355