The phase 3 KEYNOTE-A39/EV-302 study has met its dual primary end points of overall survival (OS) and progression-free survival (PFS) in previously untreated, locally advanced or metastatic urothelial carcinoma (la/mUC), according to the latest topline results.
The trial assessed the combination of enfortumab vedotin-ejfv (EV) plus pembrolizumab versus chemotherapy (gemcitabine plus cisplatin or carboplatin). Investigators enrolled patients who may or may not be eligible for treatment with cisplatin-based chemotherapy, regardless of PD-L1 status.
The combination demonstrated a statistically significant and clinically meaningful improvement in OS and PFS compared with chemotherapy in patients with previously untreated la/mUC, researchers reported. Additionally, EV plus pembrolizumab showed a statistically significant improvement in overall response rate—the key secondary end point.
The safety profile of EV plus pembrolizumab in this study was consistent with previously reported studies of this combination.
“The results of this pivotal phase 3 study are highly encouraging,” said Dr. Eliav Barr, senior vice president, head of global clinical development, and chief medical officer at Merck, in a press release. “This is an important milestone, as many patients with advanced urothelial carcinoma still experience disease progression following chemotherapy.”
EV-302 is intended to serve as the confirmatory trial for the current US Food and Drug Administration accelerated approval of EV plus pembrolizumab as first-line treatment for patients with la/mUC who are not eligible to receive cisplatin-containing chemotherapy based on data from the EV-103 dose-escalation cohorts—Cohort A and Cohort K.