Japan's Ministry of Health, Labour and Welfare Approves PADCEV™ (enfortumab vedotin) with KEYTRUDA® (pembrolizumab) for First-Line Treatment of Radically Unresectable Urothelial Carcinoma
Japan's Ministry of Health, Labour and Welfare Approves PADCEV™ (enfortumab vedotin) with KEYTRUDA® (pembrolizumab) for First-Line Treatment of Radically Unresectable Urothelial Carcinoma |
[24-September-2024] |
- Approval based on the EV-302 trial where the treatment combination nearly doubled median overall survival and significantly extended progression free survival compared to platinum-containing chemotherapy, the current standard of care for first-line treatment of radically unresectable urothelial carcinoma1 - Approval follows priority review designation from the Ministry of Health, Labour and Welfare, granted on the basis of the clinical usefulness of the treatment combination and the seriousness of the disease for which it is intended2 TOKYO, Sept. 24, 2024 /PRNewswire/ -- Astellas Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura, "Astellas") today announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approved PADCEV™ (enfortumab vedotin [genetical recombination]) with MSD's KEYTRUDA® (pembrolizumab [genetical recombination]) as a combination therapy for the first-line treatment of adult patients with radically unresectable urothelial carcinoma. This is the first approved combination treatment for radically unresectable urothelial cancer in Japan to offer an alternative to platinum-containing chemotherapy, the current standard of care for first-line treatment. In Japan, bladder cancer is the 9th most common cancer, with over 34,500 new cases diagnosed and 11,000 deaths reported from the disease in 2022.3 Particularly poor outcomes are associated with the latter stages of the disease, with global five-year survival rates of 39% and 8% for locally advanced and metastatic urothelial cancer, respectively.4 The approval by the MHLW was supported by results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) which explored the efficacy and safety of enfortumab vedotin in combination with pembrolizumab in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). Results showed that the treatment combination resulted in a median overall survival of 31.5 months (95% CI: 25.4-NR) compared to 16.1 months (95% CI: 13.9-18.3) with platinum-containing chemotherapy, representing a 53% reduction in risk of death (Hazard Ratio [HR]=0.47; 95% Confidence Interval [CI]: 0.38-0.58; P<0.00001). The median progression-free survival of 12.5 months (95% CI: 10.4-16.6) with the combination compared to 6.3 months (95% CI: 6.2-6.5) with chemotherapy represents a 55% reduction in the risk of cancer progression or death (HR=0.45; 95% CI: (0.38-0.54); P<0.00001). The safety results in EV-302 are consistent with those previously reported for this combination in EV-103 in cisplatin-ineligible patients with la/mUC. The most common (≥3%) Grade 3 or higher adverse events (AEs) related to treatment with enfortumab vedotin in combination with pembrolizumab were maculo-papular rash, hyperglycemia, neutropenia, peripheral sensory neuropathy, diarrhea, and anemia. No new safety issues were identified. During the EV-302 trial, approximately 30% of patients completed treatment with chemotherapy and then went on to receive maintenance therapy with avelumab, a PD-L1 inhibitor, which is reflective of current real world clinical practice.1 Results were presented at the 2023 European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine.1 Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas In addition to this latest approval, enfortumab vedotin in combination with pembrolizumab was approved by the European Commission in August 2024 for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer, who are eligible for platinum-containing chemotherapy. Furthermore, in December 2023, the U.S. Food and Drug Administration approved the use of the combination therapy for adult patients with locally advanced or metastatic urothelial cancer. Astellas has already reflected the impact from the approval for enfortumab vedotin in Japan in its financial forecast for the current fiscal year ending March 31, 2025. About EV-302 The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Findings from EV-302 were presented at the 2023 European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine.1 About Bladder and Urothelial Cancer About PADCEV™ (enfortumab vedotin [genetical recombination]) PADCEV is indicated in Japan as monotherapy for the treatment of adult patients with radically unresectable urothelial carcinoma that has progressed after anti-cancer chemotherapy, and in combination with KEYTRUDA® (pembrolizumab) for the first-line treatment of adult patients with radically unresectable urothelial carcinoma.13 Ongoing Investigational Trials EV-103 (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter Phase 1b/2 trial investigating enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with la/mUC and in patients with muscle-invasive bladder cancer (MIBC). Enfortumab vedotin in combination with pembrolizumab is being investigated in an extensive program in multiple stages of urothelial cancer, including two Phase 3 clinical trials in MIBC in EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303 (NCT03924895, also known as KEYNOTE-905). The use of enfortumab vedotin in combination with pembrolizumab in second-line urothelial cancer and MIBC has not been proven safe or effective. EV-203 (NCT04995419) is a Phase 2, multicenter, single-arm bridging trial in China designed to evaluate the efficacy, safety, and pharmacokinetic performance of enfortumab vedotin as treatment for patients in China. A total of 40 patients were enrolled in the trial. EV-104 (NCT05014139) is a Phase 1 trial exploring enfortumab vedotin in patients with non-muscle invasive bladder cancer (NMIBC). The trial will be conducted in two-parts, assessing dose escalation and dose expansion with enfortumab vedotin when administered intravesically as a monotherapy. EV-202 (NCT04225117) is an ongoing, multi-cohort, open-label, multicenter Phase 2 trial investigating enfortumab vedotin alone in patients with previously treated advanced solid tumors. This trial also has a cohort that is investigating enfortumab vedotin in combination with pembrolizumab in patients with previously untreated recurrent / metastatic head and neck squamous cell carcinoma. Important Safety Information About Astellas About the Astellas, Pfizer and Merck Collaboration Astellas Cautionary Notes Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice. 1 Powles T, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024;390:875-888. 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