A Trial of VERU-100 for the Treatment of Advanced Prostate Cancer – Ronald Tutrone

October 31, 2021

Alica Morgans is joined by Ronald Tutrone to provide an update on the clinical trial VERU 100. VERU‑100 is a novel, proprietary long-acting gonadotropin-releasing hormone (GnRH) antagonist peptide 3-month subcutaneous depot formulation designed to address the current limitations of commercially available androgen deprivation therapies (ADT). 


Ronald Tutrone, MD, FACS, CPI, National Medical Director of Clinical Research Chairman, Kahlert Urology Endowment at GBMC, United Urology Group

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts

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Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist at Dana-Farber Cancer Institute. I am so excited to talk today with Dr. Ron Tutrone who is the Chief of the Division of Urology at the Greater Baltimore Medical Center, as well as being the National Medical Director in Research for United Urology Group. Thank you so much for talking with me today, Dr. Tutrone.

Ronald F. Tutrone: Pleasure to be here, Alicia.

Alicia Morgans: Wonderful. So I wanted to talk with you a little bit about VERU-100, which is a phase two trial that's investigating an injectable GnRH antagonist medication, and this form actually has a duration, a depo-duration that sounds like it is about three months. So I'd love to hear your discussion first about this new medication, and then we can get into the trial. So can you tell us a little bit about it?

Ronald F. Tutrone: Sure. It is a novel GnRH antagonist, decapeptide that is delivered through a subcutaneous injection that is small volume, 1.5 ccs. It's given every three months and its purpose is to suppress testosterone in men with advanced prostate cancer.

Alicia Morgans: That's great. And one of the things that we talked about before is that other forms of GnRH antagonists have required a loading dose, whether that's the oral relugolix or whether that's the injectable degarelix. So does this form actually require a loading dose or a double dose for the first injection?

Ronald F. Tutrone: No, it does not. It's a standard dose that's given every three months. And as you said, the loading dose does have a disadvantage and specifically with the degarelix injection, it's a larger volume in divided doses and there is associated pain at the injection site. So this has the advantage of less discomfort at the injection site. And it's spread out over three months rather than having a patient come in monthly. The downside of the oral agent, not that bad having to take two extra pills on a loading dose, but there's the question of patient compliance, taking the drug every day.

Alicia Morgans: Great. Well, I love the idea of another alternative. I think it's always good for our patients to have options and for our clinicians, of course too who really want to try to optimize adherence and really get medication to patients, that's our goal, of course. So tell us a little bit about this study that is investigating this agent, VERU-100.

Ronald F. Tutrone: Sure. So it's a phase 1b/2 study. So it's really a dose discovery study to find the optimum dose that will suppress testosterone at day 28 through day 91. That's the primary objective of the study. The study does have some secondary objectives looking at the patients who achieve a super castration level, which we would consider a level less than 20. The standard castration level is 50 nanograms per deciliter. We are also looking at how many patients will achieve a lower level below 20 nanograms per deciliter. We are also looking at free testosterone levels as well as serum PSA levels, so the clinical response in men. Those are the objectives of the study, as well as the safety and tolerability of the drug.

Alicia Morgans: I think that's fantastic. And there is some evidence that having that super castrate level of testosterone suppression may be associated with better outcomes. So important for us to have that information as well. Who are you enrolling in this trial, given that it is kind of a dose-finding trial? So perhaps these men have more advanced disease, but tell us, who is this population?

Ronald F. Tutrone: So as with many trials, there are always amendments that happen. Initially, we were just testing men with newly diagnosed metastatic prostate cancer, so they had to have metastatic disease. It has been broadened now to include men who have biochemical recurrence following definitive therapy. So that would include anybody with a rising PSA who has had surgery or radiation, who we feel are good candidates to initiate hormonal therapy. They would be included in this trial.

Alicia Morgans: That's great. And I'm wondering from your perspective because you have given this agent to some patients in the clinic on the trial, how are people tolerating it?

Ronald F. Tutrone: It's really nothing different than what we've been giving. We have used standard LHRH therapy, lupron, and eligard for 30 years, and one is sub-cu, the eligard, the lupron is intramuscular and they tolerate it very well. It's very easy to administer and very well tolerated. The big advantage, Alicia, is the fact that it is given every three months, and that fits more to how we would normally like to follow our patients with advanced prostate cancer, rather than seeing them every month, we can see them every three months.

Alicia Morgans: I agree, and I remember talking to representatives from degarelix's group actually many years ago, just saying, "Can you just give us a three-month injection? It would be so much easier." So I'm glad that we have that opportunity now. And as you think about this study, and of course the next steps, what would your message be to clinicians who are interested in learning more and potentially putting patients on trial?

Ronald F. Tutrone: Yeah, that's a good question. And there are subtle advantages to using a GnRH antagonist, and I'll go through those if you don't mind me doing it because it's off the top of my head. So first, why I liked the GnRH antagonist is that you get rapid testosterone suppression without the testosterone flare that you get with the LHRH agonists. So there's no need to give them a testosterone receptor blocker to block that testosterone flare. So within a week, everybody is castrate and the testosterone drops rapidly. That's a big advantage. The second thing is testosterone recovery. And we know that patients who are put on LHRH agonists may take a long time to recover their testosterone. I did an investigator-initiated trial where I only had about 30% of patients at 18 months out, that had a recovery of their testosterone after a single six-month injection of an LHRH agonist.

Again, that's not published data, it's an in-house investigator-initiated trial. But we know, some patients have permanent castration with just LHRH agonists, given for one or two years. With the GnRH antagonist, there is a much more rapid recovery of testosterone levels when you stop the therapy. And this was shown in the recent publication in the New England Journal of Medicine of the HERO Trial, where 50% of patients were eugonadal after three months of stopping the oral agent. And this has a lot of clinical implications in patients who are receiving short-term hormone therapy for adjuvant therapy for radiation, they may be getting only six months up to two years of hormonal therapy following radiation. We know we have a lot better estimate of recovery of their testosterone levels.

The third clinical factor that's important is the adverse cardiovascular events that are associated with LHRH agonists. Again quoting the HERO Trial, where they looked at oral GnRH antagonists and compared them to LHRH agonists, there was a 54% reduction in major adverse cardiac events, such as MI, stroke, thromboembolic event, 54% reduction in the patients who got the GnRH antagonist. So, that has a lot of clinical implications as far as the safety of giving hormonal agents.

Alicia Morgans: Well, I think it is really, really important, obviously that we keep patients safe and we control their cancer when we want to stop providing a cancer-related therapy, that we are able to do so, and let them get back to normal as quickly as possible. So I think we all agree on those things and I sincerely appreciate you sharing the details of this trial and your reasoning behind using agents like this, these GnRH antagonists. Thank you so much for your time and your expertise.

Ronald F. Tutrone: Alicia, thanks so much. And it was a pleasure being here.