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Zachary Klaassen: My name is Zach Klaassen. I'm a Urologic Oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined on your show today by Doctor Luke Nordquist, who is CEO of Xcancer and a Medical Oncologist. Luke, thanks so much for joining us today.

Luke Nordquist: Zach, good to be here. Thanks for the invite.

Zachary Klaassen: So we're going to cover a couple of topics today, but we're going to start with just an update on the CLARIFY trial. I'm going to pull up the slides, and I'd love for you to walk us through the trial design for this important imaging study as we continue to see enrollment in this trial.

Luke Nordquist: So the CLARIFY study, it's from a company, Clarity, out of Australia. We've done a number of trials for them now. They're working a lot with copper isotopes. The study to CLARIFY—very important study as you mentioned. It's pre-surgery for high-risk patients. So the Gleason 8, 9, and 10, the PSA over 20, T3a or greater disease. That's the population of people that they're looking at in people that are looking to go to surgery within 90 days from being on the study.

And the purpose of this—if we look back and say, how have we done this in the past? Well, we'd get a bone scan and a CAT scan in these patients, and they're not perfect by any means. In fact, they're wrong about a third of the time and don't show disease that's there, which causes the recurrence. And it's improved with the evolution of various PET scans along the way, and more recently, the Gallium and F18 PSMA PET.

What Clarity has introduced here with the CLARIFY trial is a Copper-64 isotope, SAR-bisPSMA, which is a different chelating and linker system. And in these high-risk patients, the population that I just discussed, and the patients who go on, they get injected, they get a scan within four hours, and then they get a second scan without a repeat injection 24 hours later. And that's one of the highlighted potential benefits of the Copper-64—is the longer half-life.

So with Gallium and F18, we have about an hour to get the images in, and that's what we're stuck with. With the Copper-64, the earlier studies have been very promising in showing significant more disease that wasn't picked up at the one hour on a second day. And they've even done studies beyond the second day into the third day of imaging. So it might actually then provide more flexibility in performing the scans at a later time point on patients also.

So they're looking at 383 patients globally, currently open in Australia at three centers, in the United States at 18 centers. We've been accruing quite well to this. It's really a nice program I have with my local urologist that we work well with them, and they've sent over some of the patients. We've had some of the patients, and they go to surgery with them.

They got to compare this against a standard of truth. And in this case, it's the histopathology from the surgical specimens, from the pathology. There's three blinded, independent radiologists that are reading these scans to compare. So that's the purpose though. But I think you might have a slide with the primary endpoint or objective, is assessing the ability of this scan to detect regional nodal metastatic disease.

Ideally, we haven't seen this, but you could have showed distant metastatic also that would maybe deter somebody from even undergoing definitive therapy. But in this case, looking more for regional that would still be potentially curative but give a better idea for the surgeons on the extent of the nodal dissection that they need at the time of surgery.

Zachary Klaassen: That's great. I think before we switch gears to talk about radioligand therapy trials, when we look at—we've had several iterations of PSMA PET, obviously, now for the last several years. And some of these images are just absolutely spectacular, picking up one- to two-millimeter lymph nodes. How do you see this potentially fitting in, and what's your experience been in the trial with these images and how counseling patients?

Luke Nordquist: Yeah, I think it's fabulous. I always say it's important to get a good surgeon, but now we know it's also good to get good images before we get a good surgeon, too, because they can only see what they see on the images. And so if this is going to help dictate who really should go to surgery or radiation, who maybe shouldn't, or who would have a better chance if they knew where the disease was before surgery.

I think it's also making a huge impact. And Clarity also has trials in the recurrent setting, in people who aren't cured with surgery that have the biochemical relapse. The PSA is rising. In the past, it was a knee-jerk reaction to go to eight weeks of radiation for about a 30% chance of cure rate. If you had additional systemic therapies, you might get closer to 50%.

But now we're seeing, instead of eight weeks of radiation, if we do one of these PSMA PET scans, identify oligometastatic disease, kind of a newer term of isolated lesions, that we can then go to SBRT or cryoablation. And in our own data here, we looked at about the last 50 patients we've done this with. And if all the disease was in the pelvic area, about half of those people went to zero PSA after cryoablation or SBRT.

We also had a population of those patients who were outside—let's say in the retroperitoneal, but oligometastatic. And this is small. It's our own data. It's not been published. But when we went to cryoablation for those oligometastatic disease, none of them had a PSA reach zero. So maybe we'll learn a lot from that of who would benefit from still salvage radiation, who might benefit more from local cryoablation or SBRT.

Zachary Klaassen: Yeah, great answer. And I think you highlighted nicely the fact that we get excellent staging imaging to really direct which direction we're going with these patients.

Luke Nordquist: Absolutely.

Zachary Klaassen: Patients love it. They love having the best imaging that we have, whether it's a trial or in practice, and then using that information to properly counsel them what their options are.

Luke Nordquist: I don't know how this would be in the FDA-approved setting, but there's been a lot of concern that people bring up on the outside—oh, are patients really going to want to stay an extra day to get the PET scan? I tell you, at least in the patients I've taken care of, they have no issue. If they can get a better image that's going to better direct surgery or radiation, they're happy to stay an extra day or two, and I don't think that would be an issue going forward. I think it actually provides more flexibility for them.

Zachary Klaassen: Yeah, great point. Luke, great discussion on your show today. Thanks so much for your time and expertise.

Luke Nordquist: Anytime, Zach. Appreciate it. Thank you.