Medicine Matters oncology

Hello, my name is Tom Powles. I'm a medical oncologist from London.

Today, I'm going to talk about the EV301 study. This is a study which compares enfortumab vedotin with chemotherapy in metastatic urothelial cancer patients whose tumors have progressed on both platinum-based chemotherapy and immune checkpoint inhibitors. This group of patients is difficult to treat. Their median survival at the moment is thought to be in the region of eight months, and standard treatment as in the trial the control arm of the trial is single arm chemotherapy, paclitaxel, docetaxel, vinflunine.

Enfortumab vedotin targets nectin. It has a microtubule disrupting agent as the payload, and linker molecule in the middl-- in the middle with an antibody targeting the nectin. That's the structure of enfortumab vedotin. And it's being tested in phase two setting in this population with response rates in the region of 40%. The randomized phase iii trial had overall survival as the primary endpoint. The primary endpoint showed a survival advantage with a hazard ratio of 0.70 favoring enfortumab vedotin with median survival of approximately 13 months in the study on.

This was statistically significant. The progression free survival and response rates also favored enfortumab vedotin versus chemotherapy. The drug worked across broad subgroups of patients compared to chemotherapy. And so overall, the efficacy was clearly superior compared to the standard of care.

The tolerability profile was in line with what we expected with enfortumab vedotin. Approximately 50% of grade three or more toxicity treatment related was observed in both the chemotherapy arm and the enfortumab vedotin arm. And approximately 15% of both arms stopped treatment because of adverse events.

Treatment related deaths were in the region of 2% which is consistent with data for other drugs in this setting. Treatment related adverse events of special interest, including things like skin toxicity, peripheral neuropathy, and hypoglycemia, occurred in a manageable number of patients with enfortumab vedotin.

Overall, it's fair to conclude that enfortumab vedotin outperforms chemotherapy from an efficacy perspective. The tolerability was in line with expectations and is manageable. And so in summary, this is a new standard of care in my opinion. In this setting of patients who have previously had both platinum-based chemotherapy and immune checkpoint inhibitors in advanced urothelial cancer which will change the way we look at bladder cancer.

Enfortumab vedotin is also being investigated earlier in the disease process, and so this is probably the first step of a number of steps for this very exciting new drug. The next series of research questions for enfortumab vedotin in metastatic urothelial cancer primarily focus on moving the drug earlier in the disease process and combining with other agents. There's a very exciting front line trial of enfortumab vedotin plus pembrolizumab versus platinum-based chemotherapy in front line metastatic urothelial cancer.

There are also neoadjuvant trials, and indeed, at ASCO this year, there's also a presentation-- GU ASCO --also a presentation of enfortumab vedotin in patients whose tumors have progressed on single agent immunotherapy. So the drug is being brought earlier into the disease setting. We need to probably know more about the quality of life associated with the agent. We're going to look at that in EV301. We should also I think be looking at biomarkers associated with response and resistance.

So a huge amount of work to do. This new class of agents are really important in this disease.