Mark, let me first start with you. You presented data that sort of was looked at up to March 2026 that showed an improvement in that prostate-specific disease-free survival. But before we actually get into that, let's talk about the protocol. What do patients need to go through to get this treatment?
Mark Garzotto: Yeah, so there are three injections that are done. The injections are done into the prostate gland itself. And what's unique about that is that it tries to maximize the benefit of radiation by localizing the treatment completely within the prostate as opposed to a systemic therapy, where you may have primarily systemic symptoms and then maybe some prostate symptoms as well.
The way the injections work, the first one is typically done in an outpatient setting in the office when a patient is coming in for either their fiducial seeds, their markers that they get into their prostate placed before radiation, or potentially a SpaceOAR. So, it's done in that setting. So patient's already in the office, and it's done with a very thin needle, a spinal needle, and it's a small amount of fluid that's injected directly into the prostate. It's a total of two mLs, which is significantly less than a teaspoon, that goes into the prostate gland. The patient then takes the prodrug valacyclovir, which is used to help kill the cells when activated by the enzyme thymidine kinase that was introduced into the prostate.
They take that drug for two weeks, and then after two weeks they undergo a second injection, and this second injection occurs right about the same time that the radiation starts. They come back in, this time they're just getting the injection, and it's a simple injection. It can be done with a very, very skinny needle, the spinal needle, through either a transrectal or transperineal approach. And then they get the two ccs injected into the prostate, and then that's it at that setting. They take the valacyclovir for another two weeks, they start radiation, and then after that injection, they get their third and final injection, so two weeks after the initiation of radiation therapy. And then they'll take another two weeks of valacyclovir and the whole treatment is completed. So, the whole treatment's completed within a six-week period.
And we were talking earlier, the primary symptoms that a patient can expect to experience would be fever, chills, flu-like symptoms that last typically from one to three days, and they're low-grade.
Phillip Koo: So in total, is it two extra visits than if you were not getting this treatment?
Mark Garzotto: Correct.
Phillip Koo: All right.
Mark Garzotto: Correct.
Phillip Koo: So Tom, let's put this into perspective from a patient's point of view. Two additional visits. How do you see it, speaking on behalf of many of the patients who might consider something like this?
Tom Hulsey: I think it would be of great benefit to patients when you're talking about two to four more weeks with just minimal side effects. The side effects I compare to like someone getting a vaccine. You sometimes feel kind of lousy for a day or two. I think it very much would be very similar, and I think there'd be a lot of value with that.
Phillip Koo: So in terms of the logistics, oftentimes as physicians, we just think patients coming to the hospital, it's not that big a deal, but there are challenges. It's funny, one of the biggest complaints with patients visiting hospitals or certain centers is parking, right? You think it's something so simple, but it's a struggle. It's a stressor. So sometimes maybe two visits, is that ... Yeah, in the end it's not that big a deal if you're going to get a clinical benefit, but talk to us about the logistical aspects of something like this.
Tom Hulsey: Well, I think what you just said, when you look at the big picture of it, logistics, I think, is pretty minimal, at least from my perspective for what the trade-off is for this. Again, I don't think that would be a big issue for a patient.
Phillip Koo: Let's sort of go into the results. We don't need to get into the results because we talked about it earlier, but in general, what benefit are you seeing for patients?
Mark Garzotto: Yeah, so the primary benefit that we're seeing translating over time is a reduction in the need for salvage anti-cancer therapy and a lower risk of biochemical recurrence. So, in the intermediate-risk group, that reduction was as much as 50%, so 50% lower likelihood of needing hormonal therapy in the long run. And in that intermediate group, we actually saw statistically significant lowering in metastasis over time, so the data that we showed yesterday was a 90% reduction in metastasis.
Phillip Koo: So just to summarize that, what we're hearing is that patients are not recurring as often, so the PSA isn't coming up. They will need potentially less ADT potentially in the future. So in some ways, the number of patients that are, quote, unquote, "cured" increases. Tom, from your perspective, obviously that all sounds great.
Tom Hulsey: It sure does.
Phillip Koo: That ADT issue, how are patients dealing with the side effects of the ADT? Is there a lot of fear, anxiety? Talk to us about the perspectives from the patient lens about ADT.
Tom Hulsey: ADT is a pretty scary proposition from a patient perspective, and the reduction of it, I mean, that's a huge ... talk about trade-offs here. I think this is a great trade-off for this because there is less ADT involved, which bottom line, that affects the quality of life and that's very important to a patient.
Phillip Koo: Let's sort of dive into the patient psyche when starting what they think is curative therapy. So oftentimes patients are diagnosed, and they are choosing between surgery or radiation, and the hope and maybe the expectation is you're going to be cured and it won't come back. But I'm sure every patient is given a sort of warning that there is a certain percentage, maybe 30%, 40% of the time, where the PSA will come back. So from your perspective and all the patients that you've interacted with, how do patients go about their lives? Are they anxious about that PSA every time they're getting their blood drawn? What's sort of going through their minds?
Tom Hulsey: There is a lot of anxiety. I still go through it 10-plus years later whenever I get my PSA checked. But the numbers here, the chances though, again, that's very, very attractive from a patient perspective.
Phillip Koo: Do you ever forget about it? Do you ever forget about your PSA, but then when it comes time for it to be drawn, that's when the anxiety comes back?
Tom Hulsey: Yes.
Phillip Koo: Or is there always ... Oh, you do? All right.
Tom Hulsey: Well, I should say I try to compartmentalize, but when it's time to do it though, and then after you have the blood drawn and the waiting period and all, it's a very anxiety-filled time.
Phillip Koo: A lot of patients are concerned. As you mentioned, there's anxiety. What are some coping mechanisms that you've found helpful and you've heard from your friends and around the world about how best to deal with that type of concern and anxiety?
Tom Hulsey: Well, it's really hard, but I go back to trying to compartmentalize it, because if not, it'll consume you, consume your life. And I think the only thing you can do is really try to compartmentalize it so you can focus on other aspects of your life.
Phillip Koo: So we talked a little about adverse events. You talked about the fever, fatigue. Is there anything else in the AE profile that was reported in this trial?
Mark Garzotto: No. There was no increase in AEs compared to placebo, so there were no signals that came up in the treatment arm that weren't present in the placebo arm.
Phillip Koo: That's fascinating. Obviously that's a huge win if those receiving the drug versus those who are not are kind of getting the same types of symptoms or adverse events. From your perspective, Tom, if there is a difference, how do patients go through that mental journey when they have to make a decision whether or not to receive a drug or not regarding what could potentially happen?
Tom Hulsey: From what I understand, again, the side effects are so minimal. To me, it's not part of the thought process looking at the big picture when you're talking about the minimal side effects and reducing the need for ADT. I mean, and the chances of recurrence are much lower. I mean, I think it's a win-win for the patient.
Phillip Koo: Hypothetically, there are obviously many other trials have shown more adverse events. That's sort of more the norm than the standard. Walk us through the patient and their caregiver's thoughts on how they make decisions when there is a known increase of adverse events.
Tom Hulsey: Well, you really have to compare it to the standard of care. I mean, what level of risk are you and your partner willing to take?
Phillip Koo: I'm going to ask one last question, sort of taking a step back, a higher-level view. Immunotherapy, we've often heard of it not being as effective in prostate cancer. A drug like this is showing that immune mechanism and in many ways I think is reigniting the hope when it comes to the immune system and prostate cancer. So Mark, I'll start with you. What's your perspective on what the future might hold? And then I'll ask Tom to sort of close us out on that.
Mark Garzotto: Yeah. I think the final word is not out on immunotherapy for prostate cancer. We know that there's a drug that's approved for a treatment of prostate cancer that's immune-based, PROVENGE. So, we know that it is possible to harness the immune system to improve patient outcomes, and in that study, they showed an improvement in overall survival, so it's kind of unequivocal.
I think that there are molecular reasons that a lot of the previous studies didn't show benefit, so there are problems with a lot of the studies that have been done up-to-date. Mostly you're dealing with a cold tumor. I'll just try to simplify it, but this is a novel approach that hasn't really been tried before, and one of the things that's different about this is that you've got the addition of radiation, which helps antigen presentation. So, you're not just doing the immunotherapy, like a vaccine alone or something like that's not going to work. It's not going to get you where you need to go. You need to have a second hit for immunotherapy to work. I think that the research is pointing that there's no one hit that will accomplish that.
You got to have a two-hit approach, and this has a two-hit approach.
Phillip Koo: Yeah, I love that. I agree. There's synergies. These combinations are showing clear synergies in multiple different areas. So Tom, from your perspective, what's sort of been the thoughts on immunotherapy and prostate cancer? And now that you've learned more about the trial results from CAN-2409, what does that mean to you and the entire patient community?
Tom Hulsey: I think it's an option that should be considered, whereas maybe before, maybe not so much. But now, though, it is another option, if you will, in the toolbox of a potential solution for the patient.
Phillip Koo: Great. Well, thank you both for joining us. I think it's exciting, and it's always exciting to see new mechanisms of action. It's always exciting to see patients have more options and especially more options in this localized space, so appreciate the perspectives and yeah, I look forward to speaking with you again.
Tom Hulsey: Thank you.
Mark Garzotto: Thank you for having us.