CORE-008 Cohort A Tests Oncolytic Immunotherapy in BCG-Naive High-Risk Bladder Cancer - Trinity Bivalacqua
December 16, 2024
Trinity Bivalacqua joins Zachary Klaasen to discuss the CORE-008 trial, specifically focusing on cohort A, which examines cretostimogene in high-risk, non-muscle-invasive bladder cancer. The conversation explores this phase II multi-cohort, multicenter, open-label study that targets BCG-naive patients with CIS, with or without papillary disease. The treatment protocol involves a six-week induction course of cretostimogene followed by maintenance therapy, with the option for re-induction if needed. They discuss the potential significance of this trial in the context of ongoing BCG shortages and the future possibility of non-inferiority trials comparing cretostimogene to BCG. The study is currently in its initial stages, with sites preparing to open and the first patient treatment expected within three to six months.
Biographies:
Trinity Bivalacqua, MD, PhD, Director of Urologic Oncology, Co-Director of the Genitourinary Cancer Service Line, Abramson Cancer Center, Professor of Surgery at the Hospital of the University of Pennsylvania, Philadelphia, PA
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Trinity Bivalacqua, MD, PhD, Director of Urologic Oncology, Co-Director of the Genitourinary Cancer Service Line, Abramson Cancer Center, Professor of Surgery at the Hospital of the University of Pennsylvania, Philadelphia, PA
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Read the Full Video Transcript
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a Urologic Oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined on UroToday by Dr. Trinity Bivalacqua, Urologic Oncologist at the University of Pennsylvania. Today on UroToday, we'll be discussing SUO 2024 presentation, looking at CORE-008 cohort A and discussing cretostimogene. Trinity, thanks so much for joining us on UroToday.
Trinity Bivalacqua: Thanks, Zach. Appreciate your time. So, Zach, I'd like to talk a little bit about the CORE-008 trial, which is a phase II multi-cohort, multicenter, open-label study looking at the effects of cretostimogene in high-risk, non-muscle-invasive bladder cancer. The first cohort is a BCG-naive group. This is cohort A, in which there is CIS, plus or minus papillary disease.
But it does have to have CIS present. And what this is looking at is the effects of cretostimogene and the typical treatment course, just like we've seen in the earlier phase trials in BCG-unresponsive disease. They undergo an induction course of creto once a week for six weeks with maintenance therapy, just like the SWOG protocol, and like has been done in the previous trials.
It does allow for re-induction of creto if the patient shows no response. And this is a trial that's really looking at bringing creto into earlier-stage bladder cancer, in particular, the BCG-naive state. As you know, BCG is in a shortage. So we're all looking for alternatives that may be effective in patients that have never seen BCG but have high-risk, non-muscle-invasive bladder cancer.
Zachary Klaassen: That's great, Trinity. So I just want to go to a little bit of Q&A about cohort A. I think, if you look at this BCG-naive space, this has been sort of a space that's developed over the last, let's say, four years, with widespread BCG shortages, difficult to get patients through treatment. And we're looking for alternatives. It's become really hot in terms of research. So let's fast forward. We got a very tolerable treatment with creto.
Let's say the results are good, which we expect them to be. Where do you think this fits into the options in the BCG-naive space, to perhaps segue into gemcitabine plus docetaxel?
Trinity Bivalacqua: Yeah, I think, Zach, if the results of the cohort A trial are good and it shows that it's effective, I think at that point the question would be, do we then have to establish that it is non-inferior to BCG itself, right? So I think one of the things that we're hearing a lot about in non-muscle-invasive bladder cancer today is, once it's established in that disease state, do we then have to perform randomized controlled trials to show that it's either non-inferior or superior?
As you're probably aware, the BRIDGE trial is doing something similar to that, where you're randomizing BCG patients with high-risk, non-muscle-invasive bladder cancer to BCG or gem/doce. And this is going through the cooperative groups. So I think, before we can use it widespread, I think we first have to establish that it is either—it's non-inferior. That's typically the trials that we're typically running these days.
And if it shows that it's not inferior to BCG, then I got to tell you, the question at that point is, what do patients tolerate better? Do they tolerate creto better? Is there a better side effect profile? Are we able to give it routinely, where we don't have to worry about reducing the dose because we have a shortage? I don't think any of those things will happen with a new, novel agent. So I think, before we can move into that, it's going to be some time.
And we still have a lot of work to do. But it's really exciting to have these new agents starting to move into the early disease space because it tells us if there's activity there or not. Biologically, mechanism of action, I think we all would acknowledge that it's probably going to be effective. And there's no reason to believe it wouldn't be extremely effective at this point.
Zachary Klaassen: Absolutely. Maybe just a little update on cohort A, how many sites are open? How many patients roughly enrolled? When do you anticipate maybe we would see data?
Trinity Bivalacqua: Yeah, we're in the process of starting everything. We have sites that are in the process of opening. We have not treated a patient yet. So what we're thinking at this point is, we're hoping within the next three to six months to treat our first patient.
Zachary Klaassen: Wonderful. Trinity, thanks so much for the update on CORE-008 cohort A and for joining us on UroToday.
Trinity Bivalacqua: Thanks, Zach.
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a Urologic Oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined on UroToday by Dr. Trinity Bivalacqua, Urologic Oncologist at the University of Pennsylvania. Today on UroToday, we'll be discussing SUO 2024 presentation, looking at CORE-008 cohort A and discussing cretostimogene. Trinity, thanks so much for joining us on UroToday.
Trinity Bivalacqua: Thanks, Zach. Appreciate your time. So, Zach, I'd like to talk a little bit about the CORE-008 trial, which is a phase II multi-cohort, multicenter, open-label study looking at the effects of cretostimogene in high-risk, non-muscle-invasive bladder cancer. The first cohort is a BCG-naive group. This is cohort A, in which there is CIS, plus or minus papillary disease.
But it does have to have CIS present. And what this is looking at is the effects of cretostimogene and the typical treatment course, just like we've seen in the earlier phase trials in BCG-unresponsive disease. They undergo an induction course of creto once a week for six weeks with maintenance therapy, just like the SWOG protocol, and like has been done in the previous trials.
It does allow for re-induction of creto if the patient shows no response. And this is a trial that's really looking at bringing creto into earlier-stage bladder cancer, in particular, the BCG-naive state. As you know, BCG is in a shortage. So we're all looking for alternatives that may be effective in patients that have never seen BCG but have high-risk, non-muscle-invasive bladder cancer.
Zachary Klaassen: That's great, Trinity. So I just want to go to a little bit of Q&A about cohort A. I think, if you look at this BCG-naive space, this has been sort of a space that's developed over the last, let's say, four years, with widespread BCG shortages, difficult to get patients through treatment. And we're looking for alternatives. It's become really hot in terms of research. So let's fast forward. We got a very tolerable treatment with creto.
Let's say the results are good, which we expect them to be. Where do you think this fits into the options in the BCG-naive space, to perhaps segue into gemcitabine plus docetaxel?
Trinity Bivalacqua: Yeah, I think, Zach, if the results of the cohort A trial are good and it shows that it's effective, I think at that point the question would be, do we then have to establish that it is non-inferior to BCG itself, right? So I think one of the things that we're hearing a lot about in non-muscle-invasive bladder cancer today is, once it's established in that disease state, do we then have to perform randomized controlled trials to show that it's either non-inferior or superior?
As you're probably aware, the BRIDGE trial is doing something similar to that, where you're randomizing BCG patients with high-risk, non-muscle-invasive bladder cancer to BCG or gem/doce. And this is going through the cooperative groups. So I think, before we can use it widespread, I think we first have to establish that it is either—it's non-inferior. That's typically the trials that we're typically running these days.
And if it shows that it's not inferior to BCG, then I got to tell you, the question at that point is, what do patients tolerate better? Do they tolerate creto better? Is there a better side effect profile? Are we able to give it routinely, where we don't have to worry about reducing the dose because we have a shortage? I don't think any of those things will happen with a new, novel agent. So I think, before we can move into that, it's going to be some time.
And we still have a lot of work to do. But it's really exciting to have these new agents starting to move into the early disease space because it tells us if there's activity there or not. Biologically, mechanism of action, I think we all would acknowledge that it's probably going to be effective. And there's no reason to believe it wouldn't be extremely effective at this point.
Zachary Klaassen: Absolutely. Maybe just a little update on cohort A, how many sites are open? How many patients roughly enrolled? When do you anticipate maybe we would see data?
Trinity Bivalacqua: Yeah, we're in the process of starting everything. We have sites that are in the process of opening. We have not treated a patient yet. So what we're thinking at this point is, we're hoping within the next three to six months to treat our first patient.
Zachary Klaassen: Wonderful. Trinity, thanks so much for the update on CORE-008 cohort A and for joining us on UroToday.
Trinity Bivalacqua: Thanks, Zach.