Alicia Morgans: Hi, this is Alicia Morgans, a GU medical oncologist at Northwestern University. I am thrilled to have here with me today Dr. Josh Meeks, a friend and colleague, who is an Assistant Professor of Urology and Biochemistry and Molecular Genetics at Northwestern University. We both worked together at the Polsky Urologic Cancer Institute at Northwestern and Josh is here to talk to me today about SUO 2019. Thank you so much for talking with me, Josh.

Joshua Meeks: Thanks, Alicia. It's my pleasure.

Alicia Morgans: Wonderful. So I just wanted to continue talking about some of the things that you found most exciting and interesting. What are the greatest advances in BCG unresponsive bladder cancer from SUO this year?

Joshua Meeks: So yeah, I think, in addition to all the stuff we've talked about with Nadofaragene firadenovec (Adstiladrin®), there are some other little glimpses of information out there that were kind of reported. So Shaheen Alanee, who's at MedAcuity in Detroit had results of his IIT, which was BCG plus pembro. This has been going on for a long time. I want to say it goes back to 2013 and the thought was it's a Phase I, really primarily looking at safety. So it was a total of 13 patients that got treated. Now, once again they got six doses of BCG. Overall, he reports it was relatively safe with a 67% response rate, still had five grade 3 events, two grade 4 events, and then there were two patients who died from progression. So I think this is going to be an early sort of foreshadowing from what we're going to see with Keynote-676 with a potentially very high response rate of BCG plus IV pembro.

Once again, the thought process mechanistically is, BCG is going to bring the immune cells to the bladder and the pembro is going to keep away the immune cell exhaustion. So I thought that it was really great to see that. There are some early data from Phase III from the VICINIUM trial. And again, this is a pseudomonas toxin delivered in the bladder. Now I would contrast this with the data from Nadofaragene firadenovec (Adstiladrin®) in that the Vicinium is given two times a week for six weeks and then given six weeks afterward, weekly. So, these are 18 doses in 12 weeks. The three-month response rate was about 40%. Once again, if you'd go back to the Nadofaragene firadenovec (Adstiladrin®) data, it was closer to 58%. So far, that doesn't seem to be hitting the bar, but we don't have durability data on that yet.

And then the last thing, you know, Jim McKiernan has done a lot of work in this space. He's really been an advocate of chemotherapy. He had a triple chemotherapy regimen, which is not getting too far from what you give IV, Alicia. So it's gem, doce, and cisplatin where you give the gem and doce on different days and then the cisplatin, I think is also separate, but it's given biweekly, the cisplatin is. And people have not used the cisplatin in the bladder because of toxicity from that. So, he's been able to kind of get this to work. He's only given it to 10 patients. Of the seven who have enough follow up, two of seven have had a reoccurrence. So I don't know where the chemotherapy is going to fit in now today. And again that probably the most interesting data in this field so far, other than sort of these newer agents, are the gem-doce, which is a two-drug regimen and they just published a multi-institutional series of this.

And it's still what we give here to most patients because of the response rates about 42% at two years. And again, it's not published by pharma, it's physicians at different institutions doing this together, mostly driven by Mike O'Donnell's work from Iowa. But I'll tell you, it's very well tolerated. Patients do great and almost across the board about a 40% response rate at two years. So I think despite what we're seeing with these, with sort of industry-sponsored trials, this is still a very effective regimen. In the future, this may be what we're comparing things to.

Alicia Morgans: So remind me, these are going to be BCG unresponsive patients who are then able to get these kinds of standard chemotherapeutic agents just intravesical and how often did you say they get that?

Joshua Meeks: So it really depends. So for gem-doce, what most people do is you get six weekly doses, gemcitabine and then we empty the bladder and put the docetaxel in. So each drug is held about an hour and a half each. So it's kind of an, I mean, the patient is in your office probably about two hours. They get six weeks of therapy and then we take a look in their bladder anywhere from four to six weeks later. If they look good and there's no cancer or very minimal cancer, they go on to get a monthly maintenance regimen. And again, I tend to recommend that for patients who've not responded to BCG because number one, it's very well tolerated, it's got probably the highest response rate we've seen. I also think there may be something to letting their immune cells kind of recover. They've gotten a ton of BCG in these patients and their immune cells are very exhausted. Going to a chemotherapy-based regimen may be working in a different way, but then also it just gives their immune cells a chance to recover.

Alicia Morgans: Absolutely. So I think it's really important what you said that this may end up being our new sort of standard comparator arm for these BCG unresponsive patients and these drugs are available. So it's nice to be able to have something that's basically off the shelf potentially for use and there are some data to support that regimen that it sounds like you're already kind of using in your clinic.

Joshua Meeks: I think the only challenge for these drugs, despite the fact that they're so available is really the nursing and institutional education. Because a lot of patients around the Chicagoland area come to see us for these drugs, even though I'm certain there are cancer centers closer to them that could give them these drugs in their bladder. But they just don't have the nursing and education to be able to give these. So I still think as an organization we're probably lagging behind where we should be to potentially provide these to people closer to their homes in a pretty straightforward way,

Alicia Morgans: But really an important part of just commenting on practice patterns that even if a drug is available if you don't have the nursing staff, the training, the facilities to support its use, it's not going to be something that you can deploy in your own practice. So maybe something we should think about in terms of future education opportunities for urology practices and the nurses and other team members that work with them. So thank you for raising that very practical piece of practice that we need to always think about. So, any closing thoughts on SUO 2019 as we kind of round things out for the BCG unresponsive bladder cancer patients?

Joshua Meeks: I think this year is going to be a critical year. I think they're going to see potentially at least one, if not I would almost speculate there may be three approvals for drugs in this space, but there really hasn't been anything in a long, long time. And then I think after that it's going to be kind of on us to figure out combinations. How do we get that CR rate higher? And so it's going to be a really interesting next couple of years in this field,

Alicia Morgans: Wonderful. And lots of hope for patients to treat unresponsive BCG, unresponsive disease, but keep their bladder, which is always usually something that people want as long as they can hold onto it. So thank you for sharing these updates and we appreciate your time.

Joshua Meeks: Thanks, Alicia.