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The pivotal randomized cohort is fully enrolled in the phase 1b/2 EV-103 (KEYNOTE-869) trial assessing the first-line combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) in cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma.1
In the cohort, known as cohort K, patients are being randomized to either monotherapy with the antibody-drug conjugate enfortumab vedotin or combination therapy with enfortumab vedotin plus the PD-1 inhibitor pembrolizumab.
“Completing enrollment in this study is an important step in investigating the potential for the combination of Padcev and Keytruda to treat metastatic urothelial cancer,” Roger Dansey, MD, chief medical officer, Seagen, which codevelops enfortumab vedotin with Astellas Pharma, stated in a press release. “If results of this study are compelling, we may have the opportunity to submit them to the FDA as part of an application for accelerated approval.”
Overall, the ongoing, multicohort, open-label, multicenter EV-103 trial (NCT03288545) is evaluating enfortumab vedotin alone and with different combinations of anticancer therapies as a first- and second-line treatment for patients with locally advanced or metastatic urothelial cancer.
Based on prior results from the EV-103 trial, the FDA granted a breakthrough therapy designation to enfortumab vedotin plus pembrolizumab (Keytruda) as a first-line treatment for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy.
The designation, which will expedite the development and regulatory review of the combination in this setting, was based on findings from the dose-escalation and dose-expansion cohort A of the EV-103 trial,2 which enrolled patients with locally advanced or metastatic urothelial cancer who were not eligible for cisplatin-based chemotherapy.
The cohort included 45 patients, with a median age of 69 years. Men accounted for 80% (n = 36) of the study population and the primary tumor location was lower tract in 69% (n = 31) of patients. Sites of metastasis included lymph nodes only in 4 patients and visceral disease in the remaining 41 patients, including liver metastases in 15 patients. PD-L1 expression status by combined composite score was less than 10 in 19 patients, 10 or higher in 13 patients, and was not evaluable/available in 13 patients.
Results from this cohort showed that the combination led to an objective response rate (ORR) of 73%, comprising a 15.6% complete response rate and a 57.8% partial response rate.
“The FDA’s Breakthrough Therapy designation is based on preliminary data on the combination of Padcev and Keytruda,” Andrew Krivoshik, MD, PhD, senior vice president and head of Development Therapeutic Areas, Astellas, stated in the release. “Both Cohort K of EV-103 and our ongoing, broader phase 3 EV-302 study are evaluating this platinum-free combination in patients with previously untreated advanced urothelial cancers.”
1. Seagen and Astellas Complete Enrollment in EV-103 Trial Cohort K Combining PADCEV® (enfortumab vedotin-ejfv) With Pembrolizumab as First-Line Treatment for Advanced Urothelial Cancer. Published online October 12, 2021. Accessed October 13, 2021. https://bit.ly/3lCNKq6.
2. Rosenberg JE, Flaig TW, Friedlander TW, et al. Study EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. J Clin Oncol. 2020;38(suppl; abstr 441).