Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm on UroToday with Dr. Nick Zorko, who is a medical oncologist, professor of medicine at the University of Minnesota. Nick, thanks so much for joining us on UroToday.

Nicholas Zorko: Thanks for having me today. It's always exciting to be here.

Zachary Klaassen: We've got a great discussion on cell surface targets new one such as STEAP1. So just tell us at a high level, what these new targets are and it has really resulted a lot of phase one trials, hasn't it?

Nicholas Zorko: Yeah. We're really in an exciting time for the bispecific antibody phase here. Before, there were a lot of trials that did not work. And in the last year or so, there's been some really exciting data that's come out for phase one.

Zachary Klaassen: Yeah.

Nicholas Zorko: A great example would be AMG 509 Xaluritamig targeting STEAP1, and then there is J&J's Pasritamig that just came out at ASCO this summer targeting KLK2. And then we have Janux and Regeneron targeting PSMA as well. So exciting multiple targets, multiple shots on goal that we might get with this.

Zachary Klaassen: And we've gone from androgen receptor to PSMA and now all these other new ones. So this is really going to be the new frontier of how we're treating advanced disease.

Nicholas Zorko: I think so, as somebody in that field specifically, specifically trained to treat immune-related reactions like that. But I think it's really exciting. I think we have the preliminary data finally from multiple products to show that this is potentially viable. And I think the other thing is too, there's always been the thought that prostate cancer is immunologically cold, that it just will not respond to immune therapy, and we're starting to see this data demonstrating otherwise.

Zachary Klaassen: And I think let's dig into STEAP1 a little bit. And you mentioned AMG 509 Xaluritamig was presented last year. Really sort of like, "Oh, wow," kind of data. So just walk us through that in the mCRPC setting.

Nicholas Zorko: Yeah, so for the AMG 509 or Xaluritamig or Xalu, that was published in early 2024, and that was a phase one study, so dose finding and then finding the recommended phase two dose. It's a CD3 STEAP1 bispecific antibody, so that was given in late stage metastatic prostate cancer, so heavily pre-treated patients there. Eventually the dose was chosen to be a fourth step up, so it was 0.1 milligrams, 0.3, 1, and then 1.5, and then after 1.5, then it was spaced out to every two weeks. Responses were above 60%. I believe it was 68% for PSA50, which was a big hit from that standpoint just to see that data. And it was the first of the data out the gate showing that this was feasible and had manageable cytokine release syndrome also.

Zachary Klaassen: Yeah, no, I remember looking at the data and it was one of those moments where we thought, "Okay, this could be the next thing that we're going to run with." And that kind of leads us into a little more of today's discussion, looking at the phase 1B and the metastatic hormone sensitive setting in combination with ARPI. So just lay out that trial design for us, and I think it just recently opened, correct?

Nicholas Zorko: It just recently opened. There's one site in Switzerland. There's two sites in Australia, and then we were the first site open in the United States just a couple weeks ago.

Zachary Klaassen: Awesome. That's great.

Nicholas Zorko: So we're excited to be there. So it's the same drug, Xaluritamig. What this is now doing, taking that proof of concept from hormone-resistant prostate cancer and trying to move it into the earlier phases of can this be used earlier, can this be used safely? There are multiple other studies already with Xaluritamig. There's a biochemical relapse study. There's also a neoadjuvant study as well with Xaluritamig, but with slightly different dosing characteristics there. But really this is using this in first line metastatic hormone-sensitive prostate cancer, so high volume disease, and then it is a triplet therapy using ADT and then either abiraterone or darolutamide. The plan is to use these for one year in combination with the Xaluritamig for at least a year.

Zachary Klaassen: And we should see data maybe in the next couple of years that this would be a phase 1B, so early data.

Nicholas Zorko: Probably early data in the next couple of years. It's a year long of treatment with the triplet therapy, and then the ARPI can continue after that.

Zachary Klaassen: Okay, perfect.

Nicholas Zorko: So don't know when, but I think the data might be several years out, but-

Zachary Klaassen: Awesome.

Nicholas Zorko: ... good things come to those who wait.

Zachary Klaassen: That's right. It's been such an exciting time, especially in this new target era. Any concluding statements? Anything we haven't hit on that you want to talk about with our listeners?

Nicholas Zorko: Yeah, I think it's just a new era in the phase for immune therapy. Like I said, we thought prostate cancer was immunologically cold. There's lots of options now it appears like in study, so I think it's going to be a really exciting time to see how those shape out and what comes next in the next couple of years.

Zachary Klaassen: Very exciting. Nick, thanks for joining us on UroToday.

Nicholas Zorko: Great. Thank you for having me.

Zachary Klaassen: You bet.