Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a medical oncologist at the Dana-Farber Cancer Institute. I'm so excited to have here with me today, a good friend and colleague, Dr. Neal Shore who's the medical director of the Carolina Urologic Research Center, as well as being the CMO of urology and the surgical oncology program at Genesis Care. Thank you so much for being here with me today.

Neal Shore: Great to be with you, Alicia. Thank you.

Alicia Morgans: Wonderful. So I wanted to talk with you a little bit about a trial in progress, a really innovative design, looking at a particular population, the metastatic hormone sensitive prostate cancer population, and I'd love to hear your thoughts on this. It's the ARASEC program.

Neal Shore: Yeah, thank you very much. So we're really super excited. We've enrolled our first few patients. This is largely a US study. We're taking advantage of the great work that was done in the chartered trial and looking at the control population and the well-described, well-reviewed metrics of what happened to that control population, that patients that just got monotherapy ADT didn't get ADT and docetaxel. Our trial is for MCSCP patients. They're going to get a single arm. They're going to get ADT, plus darolutamide.

As we know, darolutamide has been approved in the non-metastatic castration resistant prostate cancer space because of the ARAMIS trial. Here in ASCO GU, we had the wonderful results of the ARASENS trial triplet therapy. But here we're looking at the doublet space and really excited. I think we know that these patients tolerate darolutamide really well. It's an active AR pathway inhibitor, so I'm hoping that we accrue rapidly. We see positive results. We compare to the historical monotherapy ADT, which is no longer really a standard of care because of all the other great advances that we've had.

Alicia Morgans: That's so important. Just to emphasize, really the new backbone, it's not so new anymore, that we've all emphasized, I think at GU ASCO 2022, is this ADT and something combination, probably ADT and an antigen receptor antagonist, or a signaling inhibitor. So tell us exactly how you're doing this work and how it might move the needle in terms of our understanding of that comparison with the control arm.

Neal Shore: Again, I would be remiss if I didn't congratulate you. In ASCO 2020, you asked me to help you with one of your fellows, Brian Shulke?

Alicia Morgans: Yes.

Neal Shore: And Carmel Pizarro. We put out some really nice work reviewing all the different combinations and why patients with MCSPC should be getting combination therapy, whether it's ADT [inaudible 00:02:47], or ADT APA, or ADT ABI, or ADT ENZA. So now we're basically trying to say, okay, let's look at ADT and daro. It just adds more to our toolbox. It gives us more optionality. Various parts of the country, various parts of the world may have certain accessibility issues. But what I've always been struck by and why I got involved in the development of darolutamide very early on and fortunate to work with Kareem Fizazi on this in the phase one, phase two studies was this notion that darolutamide really has minimal to no blood brain barrier penetration.

So a lot of the work that we've done together, and you've been phenomenal in the patient reported outcomes literature, and with your expertise, is looking at neurocognitive impairment that we see from many oncolytic therapies where we seem to see a minimal attribution of that with darolutamide. In addition, we'll be looking at cardio oncologic effects as well. So we have a really nice body of literature now with long-term data in ARAMIS and with ARASENS. I'm so happy to be leading the ARASEC trial with some fantastic US sites. We've already started accruing. I think we're going to accrue very rapidly. Assuming that it's a positive study, we have to do the study, it'll complement ARASENS, the triplet therapy very well.

Alicia Morgans: Well, that's great. So if patients, if investigators, clinicians are interested, I'm sure we will put up the clinicaltrials.gov information. So if they can find a site. Is this accruing widely across the US?

Neal Shore: Yeah, we have really good national distribution. Clinicaltrials.gov is a great location to find it. Basically, we're in every region of the country. I think we are really hoping to, because it's an open label, single arm study using this really nice opportunity to leverage the control arm from charted, and we've obviously had discussions with the agency on this, yes, that would be fantastic. That's why we have a trial in progress poster here at ASCO GU.

Alicia Morgans: Well, really just to emphasize, as we start to wrap up, that all patients on this trial will get darolutamide and of course, they'll all get ADT. So everyone will get that optimal treatment, or at least one of the treatments that they could use in the metastatic hormone-sensitive setting, but don't currently have the option to get based on the label. So everyone gets the treatment, which I think is always a good selling point when you're thinking about a clinical trial.

Neal Shore: Yeah, that's absolutely right. So thank you very much for letting me review it.

Alicia Morgans: Absolutely. Thank you for your time.