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Phillip Koo: My name is Phillip Koo and welcome to UroToday. Today we have with us Dr. Daniel Saltzstein from Urology of San  Antonio, where he serves as Medical Director of Research and also the Director of the Advanced Prostate Cancer Center.

Welcome, Dr. Saltzstein.

Daniel Saltzstein: Well, Phil, thanks for having me on today. I appreciate it.

Phillip Koo: At Urology of San Antonio, I've been enrolling patients onto this new trial called ECLIPSE. This ECLIPSE trial is really exciting and there's been a lot of buzz and excitement about this trial that's bringing Lutetium-177 to patients a little earlier.

For those who aren't familiar with ECLIPSE, I refer you to a video that was recently released that features Dr. Alicia Morgans and Emmanuel Antonorakis speaking about this. But for those who haven't seen it, can you give us a brief synopsis of the trial?

Daniel Saltzstein: Yeah. Essentially, we are looking for patients who have metastatic castrate-resistant prostate cancer that have failed one novel hormonal agent, whether that be abiraterone, whether that be enzalutamide, and they are progressing usually by RECIST criteria more than two bony lesions are appearing, something like that. Then they're going to get randomized to this unique or novel mechanism of action of using Lutetium or radioligand or the opposite novel hormone agent.

Again, the urologic community is very excited about this because we are moving up Lutetium into the treatment paradigm. Currently, it's only approved in the post-chemo setting, so the patients that we are looking to involve in this trial are in that pre-chemo space.

Phillip Koo: Great. This trial, I believe it was scheduled to enroll a little over 400 patients or so. How has enrollment been so far globally Because I believe it's a US trial and a European trial.

Daniel Saltzstein: Right. I think when I saw the most recent statistics, I think they've accrued about 330 patients to-date so they're well on their way to meeting their enrollment goal. I know Urology San Antonio has being one of their biggest enrollers and recruiters up to date.

Phillip Koo: So this pre-chemo space in that patient with castration-resistant prostate cancer is many believe that's sort of the sweetest spot for these radioligand therapies, especially Lutetium-177-PSMA. Can you talk a little bit about some of the inclusion criteria and who you envision as sort of the ideal patient for this ECLIPSE trial?

Daniel Saltzstein: Yeah. Again, I think you refer to it as the sweet spot, and I think we would agree because being pre-chemo, their bone marrow, their body's ability, they're not as quote-unquote "beat up" by the time they get to their course of Lutetium.

Again, it's that patient who you've had on a novel hormonal agent, they have castrated testosterone, and they have PSA progression, and also radiographic progression. So that is the patient that we are looking for at this point in time.

Again, they can't have had a prior radioligand. They can't have been exposed to Xofigo, they cannot have had any prior chemotherapy.

It's based on RECIST criteria. They have to have at least two new lesions to qualify for the trial, but it can be either bony or soft tissue disease. They are using either a gallium-based PSMA scan or the fluorine-based, F18-based PSMA scans are both able to or able to use both for patients to qualify.

Phillip Koo: Great. Those PSMA scans, I think it's wonderful that either of those PSMA agents can be used to qualify into the trial. What are the specific criteria on those imaging tests that would either allow them to be included or excluded to this trial?

Daniel Saltzstein: Again, I would have to go back and look. I think there's a SUV inclusion and it has to be greater than 10. They have to have at least I think two or more lesions identified on scans. Again, it can be either soft tissue or bony lesions. I do not think visceral is excluded at this point.

Phillip Koo: It's interesting with the VISION trial there was I think around 13% of patients who were PSMA-negative. It'll be interesting to see the data once it's released and all analyzed. But I imagine in this pre-chemo space, we'll see even higher number of patients who are PSMA-positive and a very small number of patients who are PSMA-negative. At least that's just my guess.

Just moving on to the logistics of this trial, how can patients get enrolled and what's sort of the treatment timeline with these Lutetium injections?

Daniel Saltzstein: Again, we have a unique setup where I'm at. We have our own radiation oncology set-up. We'll do SBRT, IMRT. We have been giving alpha and beta agents in the past, and so it requires getting a license to give it or having an affiliation with a radiation oncologist who does.

The patient will go through screening and they will get randomized two to one to the Lutetium or the opposite novel hormonal agent or androgen receptor signaling inhibitor at the time.

The medication is given four doses on an every six-week basis. Of course, they will be monitored with laboratory values, things like that, to make sure they're not having any SAEs or AEs. Then they'll be monitored on the trial with bone scans and CAT scans for progression, along with PSA.

Phillip Koo: This is interesting because in VISION it was four treatments and up to potentially six. This is just four, which I think if we're able to get those great results in four, obviously, that would be ideal so it'll be very interesting to see how this reports out.

You talked about your experience providing these unique sort of novel treatments, actually, I'm not even going to say novel anymore, these really emerging treatments in a urology practice that has a large advanced prostate cancer population working closely with radiation oncology. Can you talk a little bit about that experience? I'm sure it's a little outside of the box and maybe unfamiliar to some urologists out there, but how has your experience been and what advice do you have for other urologists or other specialties out there looking to sort of provide this type of service?

Daniel Saltzstein: Yeah. I think we are trying to achieve that goal of a very functional multidisciplinary clinic where it's not just the urologist, but it's the radiation oncologist, it's the radiologist. We've also now have a medical oncologist in our group that's helping those with either clinical trials or managing some of our advanced cancer patients.

Again, I think size matters. We're a group of 25 physicians with 10 mid-levels, like I said, so we have a very large catchment area, so a good referral base. We've elected champions within our group that help do nothing, but say the prostate cancer space and the advanced prostate cancer space. We have the same with the kidney and the bladder space. So it allows us to have a rich pipeline of patients that will be qualified for trials or that would fit into a multidisciplinary.

Phillip Koo: Great. This ECLIPSE trial I think is groundbreaking or I think it's really exciting to continue to see various companies and various compounds. This is going to be PSMA-I&T that are being investigated and, again, in all these different spaces. So we started off in that post-chemo space CRPC. Now we're moving into the pre-chemo space with I&T. Very exciting.

What are some final thoughts and sort of what keeps you so excited about radioligand therapies in prostate cancer?

Daniel Saltzstein: Well, again, I'll go back to the VISION trial and taking the very sick patients or post-chemo and seeing improvement in radiographic progression-free survival, overall survival, improvement in quality of life. So as a urologist, to be able to push this treatment option up into the treatment paradigm is very exciting.

I know that there are also trials going on in the metastatic hormone-sensitive space for a gentleman, and so I envision that we will be using this form of therapy earlier and earlier.

We are also involved in trials looking at different PSMA agents, longer half-lives. I know there's investigation also into maybe the alpha and beta particles and looking at different receptors other than the PSMA on the cancer cell, whether that be gastrin receptors looking for that, like you said earlier, that 13% that don't express PSMA on the surface. Hopefully, we'll have more options available going forward.

Phillip Koo: Great. So the ECLIPSE trial accruing very well, still some slots available. I believe they're quickly approaching their target enrollment. But for those patients or those urologists or physicians out there who are looking to enroll, go to clinicaltrials.gov. Obviously, Urology San Antonio is part of this, but there are I think around 40 sites in the US which you can find on that website where you could potentially send your patients.

Thank you very much, Dr. Saltzstein, for joining us and we appreciate your time.

Daniel Saltzstein: Thanks, Phil, Appreciate it.