• Enfortumab vedotin plus pembrolizumab continues to demonstrate superior efficacy versus chemotherapy in a broad population, reinforcing the combination as standard of care in first-line treatment of la/mUC

• At nearly 30 months of follow-up in the Phase 3 EV-302 trial, the combination doubled median overall survival and progression-free survival compared to chemotherapy, with no new safety signals identified

Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) announced additional follow-up results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) evaluating the efficacy and safety of PADCEV ^® (enfortumab vedotin-ejfv), a Nectin-4 directed antibody-drug conjugate, plus KEYTRUDA^® (pembrolizumab), a PD-1 inhibitor, in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). The results showed a sustained overall survival (OS) and progression-free survival (PFS) benefit consistent with the findings of the primary analysis after an additional 12 months of follow-up (median follow-up of 29.1 months). 

Thomas Powles, M.R.C.P., M.D., Professor of Genitourinary Oncology at Queen Mary University of London; Director, Barts Cancer Center, London; EV-302 Primary Investigator

“These latest findings from the EV-302 trial reaffirm the primary results, which demonstrated survival improvements for patients treated with enfortumab vedotin and pembrolizumab that were previously unprecedented in locally advanced or metastatic urothelial cancer. These data show that the potential survival benefit has become even more robust with extended follow up and further solidify the combination as standard of care.”

Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% confidence interval [CI], 0.43-0.61). The median OS was 33.8 months for the combination versus 15.9 months for chemotherapy. The OS benefit was observed in all prespecified subgroups, including cisplatin eligible and ineligible subgroups. Enfortumab vedotin plus pembrolizumab also reduced the risk of disease progression or death by 52% versus chemotherapy (HR = 0.48, 95% CI, 0.41-0.57). The median PFS was 12.5 months for the combination versus 6.3 months for chemotherapy. The safety profile was consistent with previous findings and no new safety concerns were identified.¹

Please see Important Safety Information at the end of this press release, including BOXED WARNING for enfortumab vedotin.

In addition to longer follow-up data, an exploratory analysis evaluating treatment outcomes and safety profile in patients with confirmed complete response (cCR) will also be presented. Among patients evaluable for response, confirmed objective response rate (cORR) was 67.5% for enfortumab vedotin plus pembrolizumab compared to 44.2% for chemotherapy. Median duration of response (DOR) was 23.3 months (95% CI, 17.8-not estimable [NE]) for the combination and 7.0 months (95% CI, 6.2-9.0) for chemotherapy. A cCR was achieved in 30.4% of patients treated with enfortumab vedotin plus pembrolizumab and 14.5% of patients treated with chemotherapy. Median duration of cCR was not reached for the combination and 15.2 months (95% CI, 10.3-NE) for chemotherapy. In patients with cCR, grade ≥3 treatment-related adverse events occurred in 61.7% of patients in the enfortumab vedotin plus pembrolizumab arm compared to 71.9% in the chemotherapy arm. There were no treatment-related deaths in the cCR subgroup.

Roger Dansey, M.D., Chief Oncology Officer, Pfizer

“Patients with bladder cancer can face a poor prognosis, particularly in the advanced stages, and until recently had few available treatment options. The updated EV-302 results show sustained long-term efficacy in a broad population that includes both cisplatin eligible and ineligible patients and reinforce this combination’s ability to reshape the urothelial cancer treatment landscape.”

Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas

“The combination of enfortumab vedotin and pembrolizumab was the first approval to offer an alternative to platinum-containing chemotherapy, which had been the standard of care for first-line locally advanced or metastatic urothelial cancer for decades. We are delighted that the additional follow-up results of the EV-302 trial show a durable benefit. These data represent yet another milestone in our long-standing commitment to helping patients around the world live longer and healthier lives.”

Enfortumab vedotin plus pembrolizumab is approved for the treatment of adult patients with la/mUC 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.