PADCEV + Keytruda improve survival in muscle-invasive bladder cancer

• PADCEV (enfortumab vedotin) plus Keytruda (pembrolizumab) is the first and only regimen without platinum-based chemotherapy to improve event-free and overall survival when used before and after surgery in cisplatin-eligible patients with muscle-invasive bladder cancer

• Positive EV-304 data, combined with the recent unprecedented results from the EV- 303 trial, highlight the potential of this combination to become a new platinum-free standard of care in an earlier stage of bladder cancer

• Results from the Phase 3 EV-304 trial will be presented at an upcoming medical meeting and discussed with global health authorities for potential regulatory filings

Astellas Pharma Co. Ltd. recently announced positive topline results from an interim analysis of the Phase 3 EV-304 clinical trial (also known as KEYNOTE-B15) for enfortumab vedotin, a Nectin-4 directed antibody-drug conjugate, in combination with pembrolizumab, a PD-1 inhibitor.

This pivotal study is evaluating the combination as neoadjuvant and adjuvant treatment (before and after surgery) versus standard of care neoadjuvant chemotherapy (gemcitabine and cisplatin) in patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy. The trial met its primary endpoint, demonstrating clinically meaningful and statistically significant improvements in event-free survival (EFS), and overall survival (OS), a key secondary endpoint.

An additional secondary endpoint of pathologic complete response (pCR) rate for neoadjuvant enfortumab vedotin plus pembrolizumab versus neoadjuvant chemotherapy was also met, and a clinically meaningful and statistically significant improvement was observed. The safety profile for enfortumab vedotin plus pembrolizumab was consistent with the known profile of the treatment regimen.

Christopher Hoimes, DO, Director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute, an EV-304 Principal Investigator “Despite available treatment options, nearly half of patients with muscle-invasive bladder cancer progress to metastatic disease within three years of diagnosis. The EV-304 results represent a key milestone in the new era of urothelial cancer treatment. Together, the EV-303 and EV-304 results show that perioperative enfortumab vedotin plus pembrolizumab can positively impact the treatment journey for patients with muscle-invasive bladder cancer, offering significant survival gains across cisplatin-ineligible and cisplatin-eligible patients, signaling a shift from conventional platinum-based chemotherapy and the potential to transform the standard of care.”

Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas “Building on the recent U.S. approval for cisplatin-ineligible patients living with MIBC, these positive EV-304 findings reinforce the potential of enfortumab vedotin plus pembrolizumab to improve survival outcomes for a broad population of patients living with muscle-invasive bladder cancer. Together with the EV-303 data, these results strengthen the evidence supporting this combination regimen as a treatment option for patients regardless of cisplatin eligibility. We are committed to bringing forth much-needed advancements and hope to more patients.

Enfortumab vedotin plus pembrolizumab is not currently approved for use as neoadjuvant and adjuvant treatment in cisplatin-eligible patients with MIBC. These results will be submitted for presentation at an upcoming medical congress and will be discussed with global health authorities for potential regulatory filings.

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About the EV-304/ KEYNOTE-B15 Trial

The EV-304 trial is an ongoing, open-label, randomised, controlled, Phase 3 study evaluating neoadjuvant and adjuvant enfortumab vedotin in combination with pembrolizumab versus neoadjuvant chemotherapy (gemcitabine and cisplatin) in patients with MIBC who are eligible for cisplatin- based chemotherapy. Patients were randomised to receive either neoadjuvant and adjuvant (before and after surgery) enfortumab vedotin in combination with pembrolizumab (arm A) or neoadjuvant chemotherapy (arm B). Curative-intent surgery (cystectomy) was performed, with patients randomised to either arm after completion of pre-operative systemic treatment.ⁱ

The primary endpoint of this trial is EFS, defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy (RC) or failure to undergo RC in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence based on blinded independent central review (BICR) or death due to any cause. Key secondary endpoints include OS and pCR rate.ⁱ

For more information on the global EV-304 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.ⁱⁱ  Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4-expressing cells, followed by the internalisation 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).ⁱⁱⁱ

For full prescribing information, including safety data, please refer to www.medicines.ie

The black triangle symbol (▼) signifies that a medicine is under additional safety monitoring by regulatory authorities. This symbol serves to encourage reporting of suspected side effects by healthcare professionals and patients. 

INDICATIONS

Padcev, in combination with pembrolizumab, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy. 

Padcev as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a programmed death receptor-1 or programmed death-ligand 1 inhibitor