Evaluating the Efficacy of Sabizabulin in The Treatment of Metastatic Castration-Resistant Prostate Cancer – Robert Dreicer
September 28, 2021
Joining Alicia Morgans is Robert Dreicer highlighting a currently enrolling Phase III trial of sabizabulin, an oral cytoskeleton disruptor in mCRPC. The VERACITY trial s a blinded trial of 245 patients randomized to two to one drug, to the alternative ARI. Dr. Dreicer describes the rationale for the trial, the trial design, and the eligibility criteria.
Biographies:
Robert Dreicer, MD, MS, MACP, FASCO is the Associate Director for Clinical Research and the Deputy Director of the University of Virginia Cancer Center. He serves as Section Head of Medical Oncology and Co-Director of the Paul Mellon Urologic Institute. He is a Professor of Medicine and Urology at the University of Virginia School of Medicine.
Alicia Morgans, MD, MPH Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts.
Biographies:
Robert Dreicer, MD, MS, MACP, FASCO is the Associate Director for Clinical Research and the Deputy Director of the University of Virginia Cancer Center. He serves as Section Head of Medical Oncology and Co-Director of the Paul Mellon Urologic Institute. He is a Professor of Medicine and Urology at the University of Virginia School of Medicine.
Alicia Morgans, MD, MPH Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts.
Related Content:
ESMO 2021: Phase 1b/2 study of sabizabulin (VERU-111), an androgen receptor transport disruptor, in men with metastatic castration resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent (ARTA)
ASCO 2021: Sabizabulin (VERU-111), an Oral Cytoskeleton Disruptor, To Treat Men With mCRPC Who Failed an Androgen Receptor Targeting Agent
NCT04844749: Efficacy Evaluation of VERU-111 for mCRPC in Patients Who Have Failed at Least One Androgen Receptor Targeting Agent (VERACITY)
A Phase 1b/2 Study of Sabizabulin, a Novel Oral Cytoskeleton Disruptor, in Men With Metastatic Castration-Resistant Prostate Cancer with Progression on an Androgen Receptor Targeting Agent.
ESMO 2021: Phase 1b/2 study of sabizabulin (VERU-111), an androgen receptor transport disruptor, in men with metastatic castration resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent (ARTA)
ASCO 2021: Sabizabulin (VERU-111), an Oral Cytoskeleton Disruptor, To Treat Men With mCRPC Who Failed an Androgen Receptor Targeting Agent
NCT04844749: Efficacy Evaluation of VERU-111 for mCRPC in Patients Who Have Failed at Least One Androgen Receptor Targeting Agent (VERACITY)
A Phase 1b/2 Study of Sabizabulin, a Novel Oral Cytoskeleton Disruptor, in Men With Metastatic Castration-Resistant Prostate Cancer with Progression on an Androgen Receptor Targeting Agent.
Read the Full Video Transcript
Alicia Morgans: Hi, my name is Alicia Morgans, and I am a GU Medical Oncologist at Dana-Farber Cancer Institute. I am so excited to have here with me today, a good friend and colleague Dr. Rob Dreicer, who is the Deputy Director of the UVA Cancer Center, as well as being a Professor of Medicine and Urology, and the Director of solid tumor oncology all at UVA in Charlottesville, Virginia. Thank you so much for being here with me today.
Robert Dreicer: A pleasure, Dr. Morgans.
Alicia Morgans: Wonderful. So I wanted to talk with you about a really interesting trial that is actually just launching, a Phase III trial of sabizabulin, which of course, I think some of us knew as VERU-111. Are you able to tell us a little bit about the drug, and the design is of this trial?
Robert Dreicer: Sure. It's an oral agent that probably is best thought of as an oral cytoskeleton disruptor. Its mechanism of action may also have some impact on AR regulation. As we know, these are somewhat theoretical constructs, but I think that is the best way to think of it.
The data that we've seen to date, and by the way, there is going to be additional data presented at ESMO in a couple of days, by my colleagues at Hopkins, to update the Phase I-II experience. But to date, the agent appears to have, the way I would think about it is, cytostatic-like activity. I think, again, that is my own perspective on the activity of the agent.
The Phase III trial, entitled VERACITY, is a relatively small trial. It is a 245 patient randomized trial, two to one drug, to the alternative ARI. Eligibility is mCRPC, castrate-resistant metastatic disease, progressing on one of the ARIs, using the alternative ARI, ABI, or ENZA presumably, for the standard of care arm.
It is not a blinded study, but the primary endpoint being radiographic progression-free survival, will be independently blindly reviewed, as the primary endpoint, and traditional secondary endpoints of a Phase III OS. And of course, all the other things that go along with it. And this trial just activated, I think there are one or two patients already enrolled.
Alicia Morgans: That's great. I guess, my first question is, are these patients post-chemo, or is this sort of a pre-chemo opportunity for patients?
Robert Dreicer: It's mostly a pre-chemo opportunity. I think that, as you are well aware, a lot of the currently either, recently reported, or ongoing trials, are really looking for that post-ARI space. And this trial is no different. One could argue that mechanism of action, because of its impact on sort of cytoskeleton, there are those who want to think about this as an oral taxane. And I don't think it's an oral taxane, but I know that some folks may think about it way. There may be a rationale to think about this agent in a taxane-naive population, but of course, all this is, time will tell.
Alicia Morgans: That makes sense. And just to that point, what does the toxicity profile look like, at this point, from the early phase data that you have?
Robert Dreicer: I think some GI toxicity. It's not been particularly myelosuppressive, really. It seems to be actually quite well-tolerated, I think. Obviously, the trials will tell us if this is a really impactful drug or not. But, as we all know, when you are talking about oral agents, if they are going to work, you also have to be able to take them long enough for them to work. So I think, the one thing we have learned from the Phase I-II experience is, that the agent is very well tolerated, and therefore, if it's going to work, and if my assessment of it being a cytostatic-like agent is real, you are going to have to be on it. So I think, that is at least a favorable thing. And obviously, Phase III will demonstrate whether that's in truth, or not.
Alicia Morgans: Well, that makes sense too. What kind of benefit, more or less, are you looking for, in terms of that ultimate comparison at the end of the study?
Robert Dreicer: I think, I'm going to refer to, try to make sure this is right, in terms of the statistical endpoint. I suspect that we are looking for about a 25% improvement in DFS, a typical hazard ratio of 0.7-ish. I think, if you have a well-tolerated drug, if you move the needle in that range, you would certainly say, it is a well-tolerated drug, that's a meaningful addition to the armamentarium, especially since, as we know, this is the same space that if you are a BRCA positive patient, we're going to be thinking about a PARP. There is a host of other AR agents, degraders, and then terminal inhibitors, everything is focused in that space. And I think that's the sweet spot. Right?
Because I think increasingly, as you well know, PROfound was updated at AUA last week. And what did we learn from that? We learned even more, that crossing over to the alternative ARI, is really not a very good idea. Then, of course, you could say, well, didn't you just design this trial with that crossover? Well, the reality is, that the trials are being designed this way because the FDA allows it. And I think that's a legitimate question. Going forward, we are going to be able to continue to use that as a control arm, but that's another story for another time.
But I think the key here is, that this agent moves the needle in this space, and it's well-tolerated. It would be, I think, an important addition to the armamentarium.
Alicia Morgans: I mean, I would agree. I think anytime we have options that might be better for certain patients, or most patients, for sure, then that's a really important thing to explore. And oral options are very, very intriguing to patients. They are definitely, I think, favored in certain ways. And I wonder too, are you integrating patient-reported outcomes into this trial? Because that's the other thing that they really look for, particularly in Phase III studies, to help them understand what their experience might be like beyond the CTCAE adverse event.
Robert Dreicer: Yeah. I think that's relatively modest in this trial, with all due respect to them. And I think part of it has to do with the size of the trial. I don't think there is any question, you of all people, know this incredibly well, that if this trial were to be positive, I suspect there are going to be subsequent efforts, because not only will, I think, the clinical community want it, but you well know, the regulatory agencies in Europe, are going to mandate that kind of information. So there's not a formal process built into this study, but I suspect that there will be more coming. And the reality is, it's a relatively small trial. So hopefully it's going to accrue rapidly, we will get a signal. If the signal is real, there's going to need to be follow-up work done.
Alicia Morgans: Absolutely. That makes complete sense. So for those patients, and for those clinicians, who want to engage in this trial, how do they make that happen?
Robert Dreicer: I think, the simplest way to do that, is to go to cancer.gov, find the clinical trial, and look for the sites. I mean, obviously, the company has a website, and likely it's listed there. But I think that, again, this trial is listed with the NCI, so the fastest way to identify a site would simply be to do that.
It is a US-based trial, so there are a number of sites around the country. Most of our colleagues, if they are interested in having a patient seen for this trial, should be able to find a site that's open. And this is a nice mixture of both large urology group practice sites, academic sites, and other oncology sites. So again, it's an admixture of centers around the US.
Alicia Morgans: That's great. And really, I think will hopefully give access to all those patients who are looking for something to go to next. So if you had to sum it up, give a final statement on the trial, what would that be?
Robert Dreicer: I would say that, for patients who are actually in good shape, who failed an ARI, this is a very intriguing agent. It has a well-tolerated toxicity profile. And because the trial is designed as a two to one randomization, and it's not blinded, the reality is, that there is no mystery here. You will know what drug you are on. So I think it's a very reasonable option for patients who are looking for something novel that may move the needle.
Alicia Morgans: Wonderful. Well, thank you so much for taking the time to design the trial, engage all the sites, and certainly, engage the patients over time. We will absolutely have to check back and hear from you, how things go over the next couple of years. And I appreciate your time today in explaining everything to us.
Robert Dreicer: It's my pleasure, Dr. Morgans. Thank you very much for the opportunity.
Alicia Morgans: Hi, my name is Alicia Morgans, and I am a GU Medical Oncologist at Dana-Farber Cancer Institute. I am so excited to have here with me today, a good friend and colleague Dr. Rob Dreicer, who is the Deputy Director of the UVA Cancer Center, as well as being a Professor of Medicine and Urology, and the Director of solid tumor oncology all at UVA in Charlottesville, Virginia. Thank you so much for being here with me today.
Robert Dreicer: A pleasure, Dr. Morgans.
Alicia Morgans: Wonderful. So I wanted to talk with you about a really interesting trial that is actually just launching, a Phase III trial of sabizabulin, which of course, I think some of us knew as VERU-111. Are you able to tell us a little bit about the drug, and the design is of this trial?
Robert Dreicer: Sure. It's an oral agent that probably is best thought of as an oral cytoskeleton disruptor. Its mechanism of action may also have some impact on AR regulation. As we know, these are somewhat theoretical constructs, but I think that is the best way to think of it.
The data that we've seen to date, and by the way, there is going to be additional data presented at ESMO in a couple of days, by my colleagues at Hopkins, to update the Phase I-II experience. But to date, the agent appears to have, the way I would think about it is, cytostatic-like activity. I think, again, that is my own perspective on the activity of the agent.
The Phase III trial, entitled VERACITY, is a relatively small trial. It is a 245 patient randomized trial, two to one drug, to the alternative ARI. Eligibility is mCRPC, castrate-resistant metastatic disease, progressing on one of the ARIs, using the alternative ARI, ABI, or ENZA presumably, for the standard of care arm.
It is not a blinded study, but the primary endpoint being radiographic progression-free survival, will be independently blindly reviewed, as the primary endpoint, and traditional secondary endpoints of a Phase III OS. And of course, all the other things that go along with it. And this trial just activated, I think there are one or two patients already enrolled.
Alicia Morgans: That's great. I guess, my first question is, are these patients post-chemo, or is this sort of a pre-chemo opportunity for patients?
Robert Dreicer: It's mostly a pre-chemo opportunity. I think that, as you are well aware, a lot of the currently either, recently reported, or ongoing trials, are really looking for that post-ARI space. And this trial is no different. One could argue that mechanism of action, because of its impact on sort of cytoskeleton, there are those who want to think about this as an oral taxane. And I don't think it's an oral taxane, but I know that some folks may think about it way. There may be a rationale to think about this agent in a taxane-naive population, but of course, all this is, time will tell.
Alicia Morgans: That makes sense. And just to that point, what does the toxicity profile look like, at this point, from the early phase data that you have?
Robert Dreicer: I think some GI toxicity. It's not been particularly myelosuppressive, really. It seems to be actually quite well-tolerated, I think. Obviously, the trials will tell us if this is a really impactful drug or not. But, as we all know, when you are talking about oral agents, if they are going to work, you also have to be able to take them long enough for them to work. So I think, the one thing we have learned from the Phase I-II experience is, that the agent is very well tolerated, and therefore, if it's going to work, and if my assessment of it being a cytostatic-like agent is real, you are going to have to be on it. So I think, that is at least a favorable thing. And obviously, Phase III will demonstrate whether that's in truth, or not.
Alicia Morgans: Well, that makes sense too. What kind of benefit, more or less, are you looking for, in terms of that ultimate comparison at the end of the study?
Robert Dreicer: I think, I'm going to refer to, try to make sure this is right, in terms of the statistical endpoint. I suspect that we are looking for about a 25% improvement in DFS, a typical hazard ratio of 0.7-ish. I think, if you have a well-tolerated drug, if you move the needle in that range, you would certainly say, it is a well-tolerated drug, that's a meaningful addition to the armamentarium, especially since, as we know, this is the same space that if you are a BRCA positive patient, we're going to be thinking about a PARP. There is a host of other AR agents, degraders, and then terminal inhibitors, everything is focused in that space. And I think that's the sweet spot. Right?
Because I think increasingly, as you well know, PROfound was updated at AUA last week. And what did we learn from that? We learned even more, that crossing over to the alternative ARI, is really not a very good idea. Then, of course, you could say, well, didn't you just design this trial with that crossover? Well, the reality is, that the trials are being designed this way because the FDA allows it. And I think that's a legitimate question. Going forward, we are going to be able to continue to use that as a control arm, but that's another story for another time.
But I think the key here is, that this agent moves the needle in this space, and it's well-tolerated. It would be, I think, an important addition to the armamentarium.
Alicia Morgans: I mean, I would agree. I think anytime we have options that might be better for certain patients, or most patients, for sure, then that's a really important thing to explore. And oral options are very, very intriguing to patients. They are definitely, I think, favored in certain ways. And I wonder too, are you integrating patient-reported outcomes into this trial? Because that's the other thing that they really look for, particularly in Phase III studies, to help them understand what their experience might be like beyond the CTCAE adverse event.
Robert Dreicer: Yeah. I think that's relatively modest in this trial, with all due respect to them. And I think part of it has to do with the size of the trial. I don't think there is any question, you of all people, know this incredibly well, that if this trial were to be positive, I suspect there are going to be subsequent efforts, because not only will, I think, the clinical community want it, but you well know, the regulatory agencies in Europe, are going to mandate that kind of information. So there's not a formal process built into this study, but I suspect that there will be more coming. And the reality is, it's a relatively small trial. So hopefully it's going to accrue rapidly, we will get a signal. If the signal is real, there's going to need to be follow-up work done.
Alicia Morgans: Absolutely. That makes complete sense. So for those patients, and for those clinicians, who want to engage in this trial, how do they make that happen?
Robert Dreicer: I think, the simplest way to do that, is to go to cancer.gov, find the clinical trial, and look for the sites. I mean, obviously, the company has a website, and likely it's listed there. But I think that, again, this trial is listed with the NCI, so the fastest way to identify a site would simply be to do that.
It is a US-based trial, so there are a number of sites around the country. Most of our colleagues, if they are interested in having a patient seen for this trial, should be able to find a site that's open. And this is a nice mixture of both large urology group practice sites, academic sites, and other oncology sites. So again, it's an admixture of centers around the US.
Alicia Morgans: That's great. And really, I think will hopefully give access to all those patients who are looking for something to go to next. So if you had to sum it up, give a final statement on the trial, what would that be?
Robert Dreicer: I would say that, for patients who are actually in good shape, who failed an ARI, this is a very intriguing agent. It has a well-tolerated toxicity profile. And because the trial is designed as a two to one randomization, and it's not blinded, the reality is, that there is no mystery here. You will know what drug you are on. So I think it's a very reasonable option for patients who are looking for something novel that may move the needle.
Alicia Morgans: Wonderful. Well, thank you so much for taking the time to design the trial, engage all the sites, and certainly, engage the patients over time. We will absolutely have to check back and hear from you, how things go over the next couple of years. And I appreciate your time today in explaining everything to us.
Robert Dreicer: It's my pleasure, Dr. Morgans. Thank you very much for the opportunity.