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Alicia Morgans: Hi, I'm so excited to be here today with Dr. Bridget Koontz, who is the Chief Medical Officer of Genesis Care in Greenville, North Carolina. And she is also the PI of a really exciting NRG phase two trial, NRG-GU-011, also called NRG PROMETHEAN. Thank you so much for talking with me today, Dr. Koontz.

Bridget Koontz: Thank you Dr. Morgan. It's really a pleasure to get to highlight our study. Thank you for the opportunity.

Alicia Morgans: Wonderful and always appreciate talking to you. And in this case we're talking about this trial in progress, so I'd love if you could set up the trial. What exactly are you studying? Who's eligible for this trial and what is happening during this study?

Bridget Koontz: The NGR Oncology GU-011 study is a phase II. It's a double-blinded, randomized trial, looking at patients who have had previously been treated for prostate cancer, but have biochemical recurrence and by PET scan have oligometastatic disease. Our study, we're defining oligometastatic disease as up to five lesions and we do want one lesion that's either in the bone or outside the true pelvis, so a true M1B case.

As you know before PET scan, these patients in that PSAs under 10 biochemical space, we didn't know where their cancer was. Sometimes we monitored them if they were unsure about going on hormone therapy, otherwise they went straight on, they went to ADT and eventually became castration refractory. But I think with PET scan, we really have the unique opportunity to find their cancer and potentially target it with radiation before it has spread widely and I think that was really the basis for why to do this trial.

Specifically in patients, one of the eligibility requirements is a PSA under 10. And specifically in that group, we really feel that the conventional imaging is typically negative, so they fit in that equipoise where there's multiple treatment options. The trial randomizes to either radiation alone and that's SBRT, a blade of dose, which we've seen through STOMP and AUREAL and SABR studies to be very good at increasing progression-free survival and versus the SBRT with Relugolix for six months. And Relugolix, we were particularly interested in because a lot of men in this cohort are really anxious around hormone side effects, so we wanted to be able to give them best options for toxicity management, either no hormones or a fast off, type of androgen deprivation and at the same time, the best options for prolongation of disease-free interval, and this is a phase two study, so we're not really looking at a survival endpoint.

That's the study. The primary endpoint is conventional progression-free survival, so we'll be monitoring these patients and really the hypothesis is that just as we've seen with curative intent, high risk prostate cancer, the combination will have a beneficial effect for progression-free survival. But we're also really the second very key endpoint is looking at the toxicity management and the symptoms. And that way we'll be able to give patients good answers about what is likely to happen to them with a pick either side of those, of the two arms.

Alicia Morgans: One thing I think that is so important to emphasize is that both of these arms are actually arms that we are using in standard of care practice every day. I have conversations with patients about using a STOMP approach, where we are trying to delay that time to systemic therapy, versus approaches where we use pharmacologic castration to just lower that testosterone, hopefully enhance the effects of the SABR and maybe prolonged time to recurrence. But we don't know the answer and these are both happening in our clinic. I love that this is a study that is trying to answer this question. Give us some insight into whether we're really shifting the disease curve and whether we can maybe do better with a little bit of hormonal therapy or maybe not, and then we don't have to use it. I think it's really, really quite an interesting study and certainly following practice in terms of using those PET scans in this setting, to understand if there are opportunities for us to use metastasis directed therapy to again shift the trajectory of our disease course.

It sounds like a great study. It is a great study, it's ongoing, but these can be challenging studies when these patients perhaps, are being seen by their urologists on a day-to-day basis and they do need to get to a radiation oncologist and maybe even to a medical oncologist depending on how the practice flow works with the systemic therapy, to potentially engage in this trial. Do you have any advice for those who are in practice as urologists, if they're interested, how do we best communicate between our practices to get people effectively onto these kinds of therapies?

Bridget Koontz: That's why we're so excited to talk with UroToday because it is, as you said, I think in my practice and in the investigators that I've spoken with, this really resonates well with patients because whether we're looking at how we manage the side effects of hormone therapy, can we delay that hormone therapy or do we want to try a novel combination of ADT and radiation? It really resonates with patients. But it is an area where we need to get the word out because there is no one standard of care and there's lots of ways to care for these patients. And so this is an option where we don't have to reflex into hormone therapy and thinking about palliative care. There is growing body of evidence that we can do more. The study is open, as you mentioned. It's available right now and there's 90 centers across the US and it is opening in Canada.

Your listeners and viewers and readers can find it on clinicaltrials.gov. If there's a center that this really sounds like a great trial and will be interested in opening it, it goes through the CTSU and we are still open for additional sites. And I think the patients to be thinking about are these folks that were, as I said, biochemical recurrence, now there's a limited number of PET lesions and what do we do? That's when getting them into one of these clinics, your radiation oncologist who can talk about whether radiation is appropriate for that patient. One of the tricks to the study is because we're comparing a hormone arm to a no hormone arm, the patients need to be hormone free at the time they enroll. They can have hormone therapy in the past, but they have to have recovered their testosterone, so that is sort of one of the challenges. We don't want to start focus if they're thinking about the study, we want to hold off on treatment until we know whether it's right for them.

Alicia Morgans: Fantastic. One other question, just logistics, is the Relugolix provided by the study or is this something that treating investigator physicians would need to get for the patient?

Bridget Koontz: No, it is provided by the study. And so that's again, a nice opportunity for patients. It's a way for them to get that drug free of charge. And it's six months, actually the radiation alone arm is a placebo arm because again, the key secondary endpoint is symptom management, so we are actually providing either Relugolix or a placebo.

Alicia Morgans: Okay, great. It sounds like interested physicians can look this up on clinicaltrials.gov, so can interested patients. They are definitely also of course looking for additional sites that want to open. That would be information that you could find on the CTSU website if you are interested in opening in your center. But with 90 sites open across the country, there is no reason that hopefully you couldn't find a place nearby to send patients and really help them contribute to our knowledge in this particular space, which is of course rapidly evolving, but also give them the opportunity to have this really exciting approach to therapy. Any final words, Dr. Koontz, as you're trying to encourage folks to think about this study?

Bridget Koontz: I think as a prostate cancer specialist and really have been very interested in how we manage all of the metastatic disease, I think there's a lot of promise in this space. It is a new cohort of patients that didn't previously exist. And as you said, that means that we really don't know the right therapy. And that's where multi-modality care and multidisciplinary care comes in and really the patient's level of interest and what their thoughts are and how they want to approach it, it all comes into play. I'm really excited that we had a chance to highlight the NRG-GU-011 study. I hope that it fits a niche for urologists, medical oncologists, radiation oncologists who are trying to figure out how to take care of that patient in front of them. And I appreciate the chance to highlight the study.

Alicia Morgans: Well, we appreciate you taking the time to talk with us about it and certainly for supporting this study and giving the opportunity for all of us to learn from this endeavor. I really appreciate it and thank you so much.

Bridget Koontz: Thank you.