Dr Robert Dreicer

As Dr Petrylak pointed out, metastatic urothelial cancer is a pretty common disease and there is very limited therapeutics. For decades, basically, front line chemotherapy was all we had. The approval of the checkpoint inhibitors was important but, as Dr Petrylak also pointed out, the response rate is basically one out of four or five people. Erdafitinib, a recently FDA approved drug, is useful in this setting, however it only impacts about one out of five patients who have a particular mutation. So new therapies are badly needed.

I’m also compelled by this data, there’s activity in patients who have received both chemotherapy or prior immunotherapy. There’s activity in hard to reach disease sites like the liver. The median survival of these patients approaches a year and, albeit it’s a phase II study, the reality is front line chemotherapy, the best we have, the median is 13 months. So the reality is, in my mind, I look at this data as effective therapy. I would support accelerated approval; I hope the FDA shares that. The confirmatory phase III will get done rapidly, hopefully. I think this is an important development for our patients.

Dr Richard Schilsky

Thanks so much. Dan, one quick follow-up question for you. You mentioned that the target, Nectin-4, is expressed in a number of different tumour types so, as far as you know, is the drug being developed in other tumour types as well?

Prof Daniel Petrylak

Yes, the phase I trial actually included ovarian and lung cancer patients. There are phase II studies that are being designed in breast cancer as well as gastric cancer. Basically anywhere that Nectin is expressed.

Dr Richard Schilsky

So that’s a particularly very high impact if studies in the other diseases show similar activity. So now is your chance to ask some questions. So please come to a microphone and identify yourself and to whom you are addressing your question.

Neil Osterweil

Hi, Neil Osterweil with Oncology Practice. A question for Dr Petrylak. Just a little bit more about the target, about Nectin-4. Is it newly discovered and you mentioned just now, Dr Schilsky asked what I was going to ask about where else it’s being tried.

Prof Daniel Petrylak

So it was discovered within the last five years and it’s expressed almost preferentially in tumour cells. Not really expressed at high levels in normal cells, in fact, a lot of normal tissue does not express Nectin. So, as Dr Schilsky pointed out, there are other studies that are going to be done – lung cancer, I believe, ovarian cancer I don’t think they’re going to be going forward with the cohort but head and neck cancer there’s a phase II trial that has now been designed for three different solid tumours.

Neil Osterweil

And how specific is the drug so that apparently you don’t get many of those off-target effects?

Prof Daniel Petrylak

The major side effects that we’ve seen include rash, peripheral neuropathy. All of these, as we’ll see in the presentation later, pretty much are reversible. We had only one toxic death that was on treatment.