– Risk of death was reduced by 53% in patients treated with enfortumab vedotin plus pembrolizumab compared to chemotherapy –

– Enfortumab vedotin plus pembrolizumab improved median overall survival by more than 15 months vs. chemotherapy

Astellas Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura, "Astellas") and Seagen Inc. (Nasdaq: SGEN)  announced results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) for PADCEV^® (enfortumab vedotin-ejfv) in combination with KEYTRUDA^®(pembrolizumab) versus chemotherapy. The combination improved overall survival (OS) and progression-free survival (PFS) with statistically significant and clinically meaningful results in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2023 as part of the Presidential Session (Abstract #LBA6).

The EV-302 study met its dual primary endpoints of OS and PFS, compared to platinum and gemcitabine chemotherapy. Patients treated with enfortumab vedotin and pembrolizumab experienced:

• Median OS of 31.5 months (95% CI: 25.4-NR) compared to 16.1 months (95% CI: 13.9-18.3) in the chemotherapy arm.
  • Significantly prolonged OS, reducing the risk of death by 53% compared to treatment with chemotherapy (Hazard Ratio [HR]=0.47; 95% Confidence Interval [CI]: 0.38-0.58; P<0.00001).
• An Independent Data Monitoring Committee determined that OS crossed the pre-specified efficacy boundary at interim analysis.
• Median PFS of 12.5 months (95% CI: 10.4-16.6) compared to 6.3 months (95% CI: 6.2-6.5) in the chemotherapy arm.
  • 55% reduction in the risk of cancer progression or death compared to treatment with chemotherapy (HR=0.45; 95% CI: (0.38-0.54); P<0.00001).
• Consistent OS results across all pre-defined subgroups, including cisplatin eligibility and PD-L1 expression level.

The most common (≥3%) Grade 3 or higher adverse events (AEs) related to treatment with enfortumab vedotin and pembrolizumab were rash maculo-papular, hyperglycemia, neutropenia, peripheral sensory neuropathy, diarrhea, and anemia. The safety results in EV-302 are consistent with those previously reported with this combination in EV-103 in cisplatin-ineligible patients with la/mUC. No new safety issues were identified.

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

Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas
"The remarkable findings presented today demonstrate that the combination of enfortumab vedotin and pembrolizumab could offer longer survival and more time without disease progression for patients with advanced urothelial cancer. The presentation of this data is an important milestone for this patient population, and we look forward to continued discussions with regulatory authorities as we work to expedite bringing this therapy to those who need it most."

Roger Dansey, M.D., President, Research and Development, Seagen
"The combination of enfortumab vedotin and pembrolizumab, if approved, represents a potential paradigm shift in the treatment of metastatic urothelial cancer. The results of this historic trial presented today show improvements in overall survival and progression free survival not previously achieved in a broad population of patients."

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
"An advanced urothelial cancer diagnosis is difficult for patients and their families, and physicians have limited treatment options for these patients. The results of this Phase 3 trial are unlike any we have seen so far and open a new chapter in advanced urothelial cancer treatment. This presents a great opportunity for this medicine to make a meaningful impact on advanced urothelial cancer patients, who face an urgent need for new therapies."

Among secondary endpoints, results demonstrated a 68% confirmed objective response rate (ORR) (95% CI: 63.1-72.1, P<0.00001) in patients treated with enfortumab vedotin plus pembrolizumab, versus an ORR of 44% (95% CI: 39.7-49.2) in patients treated with chemotherapy. In the enfortumab vedotin plus pembrolizumab arm, 29.1% of patients experienced a complete response, and 38.7% of patients experienced a partial response, compared with 12.5% and 32.0% in the chemotherapy arm, respectively. The median duration of response (DOR) was not reached in the enfortumab vedotin plus pembrolizumab arm, versus 7 months (95% CI: 6.2-10.2, P<0.00001) in the chemotherapy arm.

The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.

The EV-302 trial is intended to serve as the basis for global submissions and as the confirmatory trial for the U.S. accelerated approval of this combination. In April 2023, the U.S. Food and Drug Administration (FDA) granted an accelerated approval to PADCEV in combination with KEYTRUDA for the treatment of adult patients with la/mUC who are not eligible to receive cisplatin-containing chemotherapy based on tumor response rate and durability of response from the EV-103 trial. The EV-302 trial is part of an extensive program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Topline results of the EV-302 trial were announced in September 2023.