Martin Schoen: Yeah, thank you so much.
Tanya Dorff: So we all are hearing about how increasingly important it is for patients with metastatic prostate cancer to have NGS, both germline and somatic testing now indicated with increasing treatment options in this space. So I'm very interested in your study called STRATOS-P, which is looking at patients with metastatic hormone-sensitive prostate cancer and their genetic makeup of their tumors. What led you to want to do this study?
Martin Schoen: Thank you for allowing me to talk about this important work. We feel that the genetic information from tumors is so informative and it can let us know about the behavior beyond just specific biomarkers such as HRR deficiency and others. And that in other tumor types, you can look at the gene expression profiles or the DNA alterations to really understand sort of the long-term prognosis. And so what we have worked with is all of the veteran data across the entire country and the sequencing that has been obtained. It's a wealth of data and that our veterans are continuing to serve by allowing us to use this data.
And so we started with over 7,000 patients that we had next-generation sequencing on and we identified those with metastatic hormone-sensitive prostate cancer, which is a little bit over 2,000. And we were able to look across over 300 genes and identify 16 that were prognostic for overall survival. And we put them into categories into a favorable-risk category, an intermediate-risk category, and an unfavorable-risk category, to really understand what the long-term potential or outcomes are of patients with different ranges of genetic alterations in their tumor.
Tanya Dorff: Yes. I have heard some of my colleagues mention that even if there's not an actionable quote unquote finding, that some of the genetic information does help guide them in terms of how aggressively they might monitor someone or sort of that index of suspicion as to when they might start to progress. So what did you find in terms of these different... So you categorized into three groups based on the genomic alterations.
Martin Schoen: Yes.
Tanya Dorff: How did that play out over the course of the patient's cancer journey?
Martin Schoen: Definitely. And so traditionally we have learned about tumor suppressor genes, which are some of the ones including TP53, PTEN and RB1. And so by grouping those into different categories, we can see that patients have a shorter time on androgen deprivation therapy and are more likely to relapse. And also in some of our initial studies, we found that the patients that have tumor suppressor genes or the STRATOS-P unfavorable categorization had a larger benefit from combination therapy such as triple therapy.
Now we have small numbers so far in the VA, but it does appear that patients with a more unfavorable-risk profile seem to be having more of a benefit from increased intensification. And of course, we're going to learn more from the ASPIRE trial about this, which is stratifying based off of TSGs. But we're hoping to be able to understand not just who can benefit from intense therapy, but what I'd really like to use STRATOS-P to do is to identify those who benefit from intermittent therapy and possibly de-escalation of the treatments that they're receiving.
Tanya Dorff: That's certainly a big focus, both for patients and I think the physicians are on board with that too. We're going to hear A-DREAM presented at this meeting, the concept of someone who has a better prognosis who responds while being able to take a break and de-intensify therapy. We also hear a lot about this PSA nadir of less than 0.2 at seven months being so prognostic. How did your genomic classification interact with that?
Martin Schoen: Yes, exactly. And so we agree that PSA of 0.2, that actually is the strongest prognostic variable that exists. But we want to build on that variable. As you have mentioned, the A-DREAM study, as well as LIBERTAS and the European DESCALATE trial are using the PSA of 0.2 to identify patients for intermittent therapy. We want to also add the genomic information to that PSA of 0.2, as well as other features such as high-volume disease and age and comorbidities to really understand who is the most likely to benefit from intermittent therapy.
And we did find that there are people with an unfavorable risk that had high-risk alterations that got to 0.2. And conversely, we had patients with favorable risk that actually had a wonderful prognosis that didn't quite get to that 0.2 mark. And so that is the goal of our STRATOS-P clinical classification is to combine these things into a score to be able to identify those at the lowest risk of prostate cancer progression as well as have the longest overall survival so that we can prospectively test whether or not intermittent therapy is appropriate for those patients.
Tanya Dorff: Yeah. I was fascinated to see even some patients who achieve that nadir less than 0.2, which we know is a favorable prognosis, I guess we all maybe have someone in our clinic where they recurred and progressed fairly quickly despite achieving that. So there's got to be some way to differentiate. And it looked like your genomic categorization really might be able to do that.
Martin Schoen: Yes, it is exactly right. Approximately 10% of patients who achieve a 0.2 or lower have an unfavorable risk classification. And some of those genes included things like RB1 or the combination of TP53 and PTEN, which we know over the long term have an adverse risk and increased mortality. So we really thought that we could use the genomics to find those patients early so that we can do either more advanced therapies, or then on the converse side, as I mentioned, maybe patients didn't adhere to the therapies that they were on, but they got to a 0.5 and they have favorable risk. Maybe those are patients who we can back off a little bit.
Tanya Dorff: Yeah, that's great. And what are your plans then? How are we going to put this into a prospective action?
Martin Schoen: Yes. So we would like to propose a trial across all of the VA clinical sites to be able to enroll patients, because this is a study that doesn't have as much support from other sponsors and that we think though in our veteran population who've been asking for this and who really would like to stop some of their androgen deprivation therapy and would be willing to test it in a prospective way we'd like to do across the country be able to test patients who have the lowest risk of progression as well as those that got to a PSA of less than 0.2 and randomize them to an intermittent therapy versus the standard of care continuous to see who has the longest time to castration resistance and then as well as overall survival.
Tanya Dorff: Well, that sounds like a fantastic way to build on this observation.
Martin Schoen: Yeah.
Tanya Dorff: Thanks so much for being here today to share that.
Martin Schoen: Well, our pleasure. Thank you for allowing us to talk about our science.