Astellas Pharma Inc. today announced that Japan’s Ministry of Health, Labour and Welfare has approved PADCEVTM (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 carcinoma 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
“Today’s approval by Japan’s MHLW expands the benefits of treatment with enfortumab vedotin in combination with pembrolizumab to patients living with radically unresectable urothelial carcinoma in Japan. These patients will now have an alternative to platinum-containing chemotherapy to treat this devastating disease, helping to improve patient outcomes, extend lives and give further hope to the patients and families that we serve.”

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.

The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing 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 platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.1

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.

 

Source: astellas.com

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