Merck (known as MSD outside the United States and Canada) has reported significant positive results from the Phase 3 KEYNOTE-A39 trial (EV-302), which is a collaboration with Seagen and Astellas. This trial assessed the effectiveness of the combination of KEYTRUDA and Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate, compared to chemotherapy (gemcitabine plus cisplatin or carboplatin) in patients with previously untreated locally advanced or metastatic urothelial cancer.
The first analysis from this trial demonstrated a remarkable 53% reduction in the risk of death when KEYTRUDA plus enfortumab vedotin was compared to chemotherapy. This translates to a median overall survival of 31.5 months versus 16.1 months, marking an improvement of over 15 months.
In addition, KEYTRUDA plus enfortumab vedotin also led to a significant enhancement in progression-free survival, reducing the risk of disease progression or death by 55%, with a median PFS of 12.5 months versus 6.3 months with chemotherapy.
These results remained consistent across various subgroups, regardless of patient eligibility for cisplatin-based chemotherapy, PD-L1 expression levels, and the presence of liver metastases.
KEYNOTE-A39 represents a pivotal study that will support global regulatory submissions and serve as the confirmatory trial for the current accelerated approval of KEYTRUDA plus enfortumab vedotin as the first-line treatment for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This accelerated approval was based on data from the KEYNOTE-869 trial.
Based on the positive results from KEYNOTE-A39, the FDA has granted priority review for the use of this combination therapy in advanced urothelial cancer patients who have not received prior systemic therapy. The data from KEYNOTE-A39, a Phase 3 trial, is particularly significant because it represents the first positive Phase 3 results that combine a PD-1 inhibitor and an antibody-drug conjugate in patients with advanced urothelial carcinoma.
These results have the potential to transform the treatment landscape for previously untreated patients with advanced urothelial carcinoma, offering new hope for improved outcomes. According to Dr. Thomas Powles, the primary investigator for the KEYNOTE-A39 trial, these findings hold great promise for patients diagnosed with advanced urothelial carcinoma. He highlighted the urgency for new treatment options in this patient population, and the substantial reduction in the risk of death observed in combination therapy is indeed a remarkable development.
These results are a significant step forward and may bring much-needed advancements in the treatment of patients with advanced urothelial carcinoma who have limited options following the failure of traditional therapies.
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