Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist on UroToday with Dr. Jerry Andriole, who is a urologic oncologist in St. Louis, Missouri. We're going to talk today about ASCO 2025 data looking at the effective resolution of bone metastases in patients with metastatic prostate cancer using SYNC-T therapy SV-102. Some really exciting data presented by Dr. Andriole. Jerry, thanks so much for joining us on UroToday today.

Gerald Andriole: Zach, I really appreciate it. Appreciate the opportunity to spread the word about this new therapy.

Zachary Klaassen: Absolutely. You got some great slides, so walk our listeners through the thought process behind this therapy, the study you guys had conducted, and the awesome results.

Gerald Andriole: Well the first thing I want to do is describe this treatment because it is rather unique.

Zachary Klaassen: Sure.

Gerald Andriole: This slide shows conceptually what happens. So we perform cryolysis. Now, you may hear me refer to it as cryoablation, but that's just out of habit because we do that a lot. But this is cryolysis, a small portion of the tumor, usually no more than a cubic centimeter or so, is frozen for only one minute. It gets a passive thaw cycle after that. And then we immediately instill in the middle of that lytic zone, a four-component immunoadjuvant drug, and that synchronizes simultaneously the new tumor antigens that the cryolysis has released with these immunoadjuvant agents. They very rapidly traffic to the regional lymph nodes where the magic happens and new T-cell clones are generated by the presence of the neoantigens and the immunoadjuvants.

Now, this is not going to tax the technical abilities of any urologist because all it calls for is the ability to localize prostate cancer and transperineally put a cryo needle directly into the center of the primary tumor. In the case of a radiologist, we also have done a similar procedure to regional lymph nodes and to soft tissue components of bone metastases. We are working on a new needle that can go through bone and we can actually treat some of the bone metastases as well. Because all of us urologists are interested in devices, this is the appearance of the AccuLyse System. This is the generator. It's very simple to operate. It's not as fancy and sophisticated as some of the other cryo devices. But the real wisdom is in the cryo needle, which you can see down below. You may notice that it's a conventional cryo needle for the most part, over which we've backloaded an infusion catheter. So the tip of the cryo needle is placed into the tumor. You get the one-minute freeze followed by the thaw, after which you then advance the infusion sheath right up to the end of the cryo needle tip.

And then there's a pump, it's not shown on this picture, that infuses the immunotherapeutic four-component drug right into the lytic zone over 10 to 15 minutes time. The whole procedure takes about 20 minutes skin to skin and can be done under conscious sedation in a surgery center, an outpatient facility or in the OR. The results we have thus far are from a phase 1 trial, and this consisted of 15 patients. You can see the schematic of the treatment down below. These were patients with metastatic prostate cancer, and the protocol allowed treatment of the primary tumor and/or lymph node metastasis, soft tissue metastases every four weeks for up to 12 cycles. I will say that many of these patients had rather large primary tumors in their prostate. We were able to treat the component of the tumor that was at the left base the first time, then the component of the tumor that was on the left apex or the right base or the right... For many of these patients, since these prostate cancers are so heterogeneous, we felt it was valuable to use cryolysis in different regions of a given primary prostate cancer so that we can maximally generate new T-cell clones that would be effective.

The same was true for enlarged regional lymph nodes and that soft tissue component. We're probably releasing slightly different antigens if there are different tumor clones causing the metastasis at each of those locations. Here are the results. The first bullet shows that 8 of the overall 15 patients achieved a complete response. Second bullet and the subject of this abstract is that 13 of those 15 patients had bone metastases, and you can see that they had rather bulky number of bone metastases. Third bullet down, 7 of the 13 men with bone metastases or 54% had complete resolution of all bone metastases after treatment. The median time to treatment response was about three months. So most patients got two or three treatment cycles and then we observed a response. The last time we looked, which was in late October of this year, four of the seven patients whose bone metastases completely resolved still had no evidence of recurring prostate cancer. All of that's on the left side, and you can see the characteristics of the individual patients on the right side of that table. One picture is possibly worth 100,000 words. We're comparing the pre-therapy May 2023 coronal PSMA PET in the first two images. You can see in May versus December.

Then you can see on the sagittal, again, May versus December, complete resolution in this patient who had numerically more than 50 bone metastases. This patient to this day still has no evidence of radiographic recurrence, he's still alive, and it's close to two years for him. No story about a treatment would be complete without giving attention to the side effects. You can see here that there were a rather modest number of treatment-emergent adverse events. 95% of them are grade 1 or 2. There were only two immune-related adverse events such as hypothyroidism and hepatitis or this autoimmunity that can be generated. The reason for that is that the dose of the immune agents that we are instilling into the lytic zone of the tumor is fractional in relation to the dose that a person would take systemically. The blood levels and the overall amount of medication is much lower with this route of administration. In summary, this we felt was a highly encouraging result. It appeared to be safe.

It appears to have some significant effectiveness. The most important thing for our listeners is that we have initiated a phase 2 trial in men with metastatic castrate-resistant prostate cancer. We've enrolled a number of patients. We are still considering enrollment of new sites. If there is anyone interested in potentially participating in this, I'd really appreciate it if they would get in touch. So thank you. Appreciate the opportunity to talk about this exciting treatment.

Zachary Klaassen: Absolutely. Jerry, fantastic data. We've heard a little bit about SYNC-T SV-102 after ASCO. This data is just... I mean, to say it's super impressive is almost an understatement. When you look at response rates of 87% in the mCRPC setting, we obviously have a lot of work to do to keep things moving along with this therapy, but the beauty of these discussions is we can sort of surmise what may come down the pipeline. In your mind, when we think about deescalation therapies, especially people that have been on, whether it's in the metastatic hormone-sensitive setting or the mCRPC setting, they've been on therapy for a long time, they're doing well. Could we potentially use this as a deescalation therapy? Could we get them off of therapy? What sort of direction do you think this could go to not only improve quality of life, improve overall survival, but maybe get off some of the toxic therapies we're giving these patients?

Gerald Andriole: Zach, you're spot on. I think that's what the real unmet need is in treating men with prostate cancer at virtually every stage of their disease. If the data of the phase 2 study hold, our next step is to treat earlier stage disease, not just hormone-sensitive metastatic prostate cancer, but also high-risk localized prostate cancer because that may well be an unrecognized systemic disease, as you well know. Furthermore, if the data continued to hold, I think we should bring this treatment to other tumors. The one that I'm thinking of most for urologists is renal cell carcinoma, which as you know, has an interesting immunologic response rate to some agents.

Zachary Klaassen: Absolutely. When we think about, do you guys have any idea whether ... It's obviously small numbers still, whether it works better if we treat the primary, if we treat a lymph node, we treat a bone metastases, is that still to be figured out?

Gerald Andriole: Yes, we need to work on that. Our impression is that we have to treat diverse sites to maximize the tumor response. That's why we would purposefully select to treat different components of the primary tumor and different involved lymph nodes or other soft tissue sites just to maximize the antigens that we create so that we can generate more and more T-cell clones that respond to those antigens as foreign.

Zachary Klaassen: Absolutely. Before we wrap up, I just want, maybe if you don't mind highlighting a little more on LEGION-100, how many patients, primary endpoint, when maybe see data from that trial?

Gerald Andriole: We're still enrolling. The FDA asked us for a dose-escalation study. We have three doses. The one we use in the phase 1 study is the middle dose. There's one that's about a third lower and another that's a third or slightly more higher. That's a study that's completely enrolled. We think within the next two to three months, we'll be able to pick the two largest doses with no toxicity or with very similar toxicity. Then we are planning to randomly assign 52 patients after that, so 26 in each of these treatment arms. It all depends upon how fast we can identify these patients. That's why I like to put a call out for new sites.

Zachary Klaassen: Absolutely. Well, we'll certainly look for that data and we really appreciate your time. Any concluding statements, any take-home messages, maybe anything we need to hit on still?

Gerald Andriole: No, I really feel this is potentially an extraordinarily important thing for urologists to be engaged in because we establish a rapport with our men when we diagnose prostate cancer, we may treat them or we may guide their treatment selections, and they have faith and confidence in us, and we know our patients well. It would be nice to be able to continue to monitor and treat them throughout the full spectrum of that disease if that's necessary.

Zachary Klaassen: That's well said. Jerry, thanks so much for joining us on UroToday. I really enjoyed the discussion.

Gerald Andriole: My pleasure. Thanks a lot, Zach.