The single-arm, phase II EV-201 trial showed treatment with enfortumab vedotin—an agent targeting Nectin-4, a protein found in 97% of urothelial cancers—produced responses in 44% of patients with locally advanced or metastatic forms of urothelial cancer. Patients had previously been treated with platinum chemotherapy and a programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitor and had disease progression after their previous treatment. These findings were presented by Petrylak et al (Abstract LBA4505).
“These phase II results replicate the phase I results very closely, which is not often the case in clinical trials,” said lead study author Daniel P. Petrylak, MD, Professor of Medicine (Medical Oncology) and Urology at Yale Cancer Center, New Haven, Connecticut. “The fact that we have a therapy that can help people who don’t benefit from checkpoint inhibitors is very gratifying.”
Phase I trial results of enfortumab vedotin provided sufficient evidence that the drug was safe to administer. In March 2018, the U.S. Food and Drug Administration granted enfortumab vedotin Breakthrough Therapy designation for people with locally advanced or metastatic urothelial cancer that has progressed during or following checkpoint inhibitor therapy.
In the phase II portion of the trial, investigators enrolled patients who had been treated with platinum-based chemotherapy and/or checkpoint inhibitors to two groups: group one had been previously treated with both kinds of agents, and group two consisted of people who had not received platinum chemotherapy. Only results from the first group—patients treated with platinum-based chemotherapy and checkpoint inhibitors—are currently being reported.
In group one, 70% of enrollees were male and the median age was 69; 35% of people had cancers in their upper urinary tract; and enrollees had a median of three prior systemic treatments in the locally advanced or metastatic setting, but had not received treatment for at least 2 weeks prior to enrolling in this trial.
Approximately 44% of patients responded to enfortumab vedotin, resulting in either no growth or shrinkage in their tumors, and 12% had a complete response with no detectable sign of cancer. The median overall survival was 11.7 months. Among patients who had not responded to a checkpoint inhibitor, 41% responded to enfortumab vedotin, and 38% of patients with metastases to the liver responded to enfortumab vedotin.
Enfortumab vedotin was well-tolerated among patients enrolled in the trial. The most common side effects included fatigue (50%), alopecia (49%), and decreased appetite (44%).
A phase III study to confirm these findings is now underway. A second group is still enrolling in the trial.
There is also a trial in progress to look at the benefits of providing enfortumab vedotin for patients newly diagnosed with advanced urothelial cancer. It is studying enfortumab vedotin in combination with pembrolizumab and enfortumab vedotin in combination with a platinum-based chemotherapy.
Disclosure: This study received funding from Seattle Genetics and Astellas Pharma. For full disclosures of the study authors, visit coi.asco.org.
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