Medicine Matters oncology

My name is Dr. Jonathan Rosenberg, and I am the chief of the Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center in New York City. And it's my pleasure today to talk to you about the results of EV-103. This is a phase 1b study of enfortumab vedotin and pembrolizumab in patients with cisplatin-- who are cisplatin ineligible with metastatic urothelial cancer.

Patients who are not eligible to receive cisplatin-based therapy generally receive carboplatin-based treatments or single-agent immune checkpoint inhibitors. On average, the outcomes for patients with carboplatin-based therapies are relatively poor, and there's a big unmet need for better treatment options for those patients. Enfortumab vedotin is an antibody drug conjugate that was recently approved in the United States by the FDA under an accelerated approval to treat patients with both immunotherapy- and chemotherapy-resistant urothelial cancers.

The study I'm presenting today is updated data from the first line study of enfortumab vedotin and pembrolizumab in cisplatin-ineligible metastatic urothelial bladder cancer patients. These patients meet criteria for cisplatin ineligibility based unimpaired renal function, impaired performance status, neuropathy, et cetera. These patients were enrolled and treated in a phase 1b study, an expansion cohort. A total of 45 patients were treated.

The drug was administered day 1 and 8 every 21 days, and pembrolizumab was administered once every 3 weeks. The objective response rate of patients on this trial was 73.3%, which is a little higher than the most recent update from ESMO 2019. And this is due to increased numbers of responses among patients that were treated on the trial as time has gone on.

In addition, the median duration of this response has not been reached, and it appears to be at least 10 if not 12 months if not even longer. The median progression-free survival in patients treated in this 45-patient cohort was 12.3 months. And to put that in context, the median progression-free survival with gemcitabine and carboplatin is approximately 4 to 6 months. So almost a doubling of progression-free survival compared to what would be considered the standard treatment option.

In addition, the median overall survival is not yet reached, and over 80% of patients were alive at the one-year landmark. There were no new treatment-emergent toxicities noted different than what you might expect from the single agents alone. There were the usual suspects in terms colitis, rashes, peripheral neuropathy-- things that you might expect from each drug by itself, but not at higher rates and not really new toxicities. There were some asymptomatic lipase elevations that had no clinical consequence, and patients were able to continue treatment.

So in summary, this was a seemingly highly active doublet regimen of a checkpoint inhibitor plus a novel antibody drug conjugate. The hope is that this will prove itself in a larger trial. And there's currently a plan for a randomized phase 3 trial comparing enfortumab vedotin either with or without platinum-based chemotherapy compared to gemcitabine and platinum in patients with metastatic urothelial carcinoma. It might establish a new platinum-free option for patients with untreated metastatic urothelial cancer.