Zach Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist in Augusta, Georgia. We are live at ASCO 2024 in Chicago, and I'm delighted to be joined today by radiation oncologist, Dr. Karen Hoffman from MD Anderson Cancer Center. Karen, thanks so much for joining us today.

Karen Hoffman: Thank you so much for having us, and thank you for your interest in our trial.

Zach Klaassen: Yeah, we're going to discuss your guys' trial in progress, which is really cool. It's basically called the PROSTATE-IQ trial and trying to decrease the burden of ADT in men that are getting salvage radiotherapy. So just give us a little background on what that burden of disability is when we're giving men ADT for salvage radiotherapy.

Karen Hoffman: Absolutely. So, testosterone suppression is a critical component of the treatment. We know that it really improves outcomes for select men, but it does have an impact. It's a burden on quality of life that causes tiredness, hot flashes, impacts sexual interest, sexual function, really cognitive function, can cause weight gain, and body composition changes. So we certainly use it when we need to, but we're very mindful about how we need to reduce the burden on our patients and the impact on quality of life.

Zach Klaassen: Absolutely. So give us a little background on how PROSTATE-IQ came to fruition. What was the background for designing this trial?

Karen Hoffman: Sure. So we had a trial prior to this in this space, the FORMULA 509 trial that was very successful and really illustrated the benefit of more intense androgen access therapy for certain patients. Specifically, for those patients with a PSA greater than 0.5, the more intense androgen access therapy improved the metastasis-free survival. So we really wanted to both identify those patients that benefited from more intense therapy, but at the same time, we were very mindful of how testosterone suppression impacts quality of life and the burden of treatment. So at the same time, we really wanted to try to look for ways to reduce that burden for patients. And so we're really able to link both together in this trial.

Zach Klaassen: That's cool. Now let's get into the really cool stuff. So we're talking about incorporating ArteraAI Prostate Test, which is the first trial to my knowledge, using the test in a clinical trial. So how are you guys using the ArteraAI Prostate Test in your trial?

Karen Hoffman: Sure. So in this study, we're really risk stratifying all patients and the ArteraAI Post Prostatectomy Test is a critical component of that. So all patients have their prostatectomy samples analyzed with the ArteraAI Post Prostatectomy Test. And so that's one main component actually what we're using to risk stratify. And we're also using some clinical features. So they're classified as Artera Low if the ArteraAI Post Prostatectomy Test is a low score and they are classified as higher risk if the ArteraAI Prostatectomy Test is a higher score or if the PSA is greater than 0.5 or if they've had clinical or pathologic nodal involvement.

Zach Klaassen: Got you. So that's really taking data that we just saw at AUA and incorporating it right into this trial, which is cool.

Karen Hoffman: Yeah, it is really cool. So it's the first North American trial that uses this test and we were really able to incorporate it early, is really early adoption of the test.

Zach Klaassen: So the second cool part of this trial is you guys are looking at traditional ADT, but also using Apa without any other ADT. So tell us about how that's incorporated in the trial.

Karen Hoffman: Sure. So we're looking to use apalutamide-based treatments to reduce the burden of therapy. So for the less aggressive patients, the Artera Low patients, they're randomized between, we consider standard six months of traditional ADT or six months of apalutamide. With the six months of apalutamide, men should have fewer side effects of treatments. They should have less tiredness, less impact on kind of intra-sexual function as well as the other components that we're looking at. So we really like that we're able to look at that for these patients. And then in the other group of patients in the higher risk patients, we're looking at two different strategies to intensify ADT because we do think that it can benefit these patients, improve their metastasis-free survival.

So we're comparing the six months of intensified ADT kind of a strategy like FORMULA 509 but the medications aren't exactly the same, so six months of ADT plus apalutamide. And we're comparing that to the other strategy that's been shown to be beneficial over six months of ADT, which is a lengthening ADT, which was the winning arm of RADICALS-HD. So 24 months of ADT compared to six months of more intensified ADT, six months of ADT plus apalutamide. And what we believe is that if you have a shorter, more intense ADT regimen, ultimately you'll have a better quality of life sooner because your testosterone will rebound faster. So we anticipate by later time point 24 month time point, and even some time after that, those men will be feeling better.

Zach Klaassen: That's great. So really taking trials that have just been published and data from ArteraAI prostate tests that's just been presented incorporating into new trial design, which is cool. Tell us about the clinical outcomes you guys are looking at, but also there's some really cool quality of life aspects you're looking at as well.

Karen Hoffman: So we felt improving quality of life was really a main driver of this study, both by tailoring treatment intensity and then looking at those alternative regimens. So with regards to the outcomes for this study, the primary outcome, we chose to actually be a patient-reported outcome, which is fatigue assessed by a questionnaire. We're also looking at fatigue and activity using patient wearables. So they'll wear wearables for about a week for 24 hours a day, so we can collect that information. We're looking at patient-reported quality of life, including EPIC-26, FACT-P. We're also collecting other questionnaire, quality of life information from our patients, looking at kind of body composition changes for our patients as well. And then with regards to cancer control, which is also critically important to understand, we're really looking at progression-free survival, metastasis-free survival, as well.

Zach Klaassen: That's great. So tell us about the outcomes for this trial. You guys have some pretty cool quality of life outcomes and obviously there's clinical outcomes as well.

Karen Hoffman: Absolutely. So we chose to do quality of life as a primary outcome for the study because it was a really important thing that we're trying to improve for these patients. So the primary outcome for this study is actually fatigue, which we're assessing by our questionnaires. And we picked that because we had actually done structured interviews of men getting ADT, and they actually reported the most concerning symptom they were having was tiredness. So that motivated us to use it as the primary outcome. Other things that we are looking at are patient-reported quality of life, including EPIC-26, FACT-P. We're having patients wear wearables for a week at a time so we can really capture their activity and their sleep because it impacts sleep. We are assessing cognitive outcomes of our patients as well and assessing the body composition. And then we're certainly looking at cancer control because that's a critical thing to understand, including progression-free survival, and metastasis-free survival.

Zach Klaassen: That's great. Where does the PROSTATE-IQ study stand at this point? How many centers are being enrolled? How many patients are you actively recruiting already?

Karen Hoffman: So the study is IRB approved. We're fortunate to have financial support from Janssen for the study, and ArteraAI is providing the post-prostatectomy tests for us. So we're ramping up enrollment at MD Anderson, which is the primary site. And then we're looking to expand nationally across our MD Anderson network, which will add an additional five sites to OhioHealth, Dana-Farber Cancer Center, Memorial Sloan Kettering. And then we're also looking to add an additional two sites. So really expanding enrollment at this time.

Zach Klaassen: And when do we expect to maybe see some initial results? Couple of years?

Karen Hoffman: In a couple of years, yes. So for the Artera Low cohort, since that's six months of treatment, we expect to report out in about three years. And then for the higher risk cohort, since some of that treatment lasts for up to 24 months, we anticipate reporting out in about five years.

Zach Klaassen: Excellent. It's been a great discussion. This is an exciting trial. I'm excited to see the results. Maybe a couple of take-home points for our listeners today.

Karen Hoffman: Absolutely. So the first one is, if possible, enroll your patients in this study. We really believe it will help us reduce the burden of treatment and really match treatments better for what patients need. And then the second I think is just within our clinical practice to really be mindful about how we're using ADT with radiation for these patients because it can really impact them.

Zach Klaassen: Absolutely. Karen, thanks so much for your time and expertise today.

Karen Hoffman: Thank you.

Zach Klaassen: Thanks.