CORE-008 Cohort B Tests Cretostimogene’s Efficacy in High-Risk, Non-BCG-Responsive Disease - Trinity Bivalacqua
December 16, 2024
Zachary Klaassen and Trinity Bivalacqua discuss Cohort B of the CORE-008 trial, which examines cretostimogene in BCG-exposed patients with high-risk non-muscle invasive bladder cancer. The phase 2 multi-cohort, multicenter study focuses on patients who have recurrent high-grade disease but do not meet BCG-unresponsive criteria. The treatment protocol includes a six-week induction course of cretostimogene followed by maintenance therapy, with endpoints measuring complete response, duration of response, and survival metrics. The discussion highlights the particular interest in papillary-only disease patients, who have historically shown better response rates in BCG-unresponsive trials. The study is set to launch at more than ten diverse sites across academic centers, large urology group practices, and VA facilities, with an emphasis on including diverse patient populations to ensure real-world applicability of the results.
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
Related Content:
SUO 2024: CORE-008: A Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants with High-Risk NMIBC
CORE-008 Cohort A Tests Oncolytic Immunotherapy in BCG-Naive High-Risk Bladder Cancer - Trinity Bivalacqua
SUO 2024: CORE-008: A Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants with High-Risk NMIBC
CORE-008 Cohort A Tests Oncolytic Immunotherapy in BCG-Naive High-Risk Bladder Cancer - Trinity Bivalacqua
Read the Full Video Transcript
Zachary Klaassen: Hello, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia, delighted to be joined on UroToday by Doctor Trinity Bivalacqua, urologic oncologist from the University of Pennsylvania. Today we're going to be discussing an SUO 2024 presentation, looking at the trial design for CORE-008, specifically Cohort B, looking at the impact of cretostimogene in BCG-exposed patients.Trinity, thanks so much for joining us on UroToday.
Trinity Bivalacqua: Thanks, Zach. Appreciate you having me here today. I'd like to talk a little bit about the phase 2 multi-cohort multicenter trial looking at the effects of cretostimogene in patients with high-risk non-muscle invasive bladder cancer.I'd like to talk a little bit about Cohort B, which is a trial looking at the effects of cretostimogene in patients that are termed BCG-exposed. These are patients that do not meet the BCG-unresponsive definition but do have recurrent disease which is high-grade.
In the Cohort B study, these are patients that will have CIS or papillary-only disease. So you could have only CIS or just high-grade papillary disease only. And they will undergo typical treatment with an induction course of cretostimogene weekly for 6 weeks and then a maintenance course weekly, per the SWOG protocol. This is identical to that of previous phase II trials in which creto was tested in patients with BCG-unresponsive disease.
The endpoints are those that are a complete response, a duration of response, recurrence-free survival, and cystectomy-free survival. Now, this is a disease space that we are currently looking at multiple different treatment options. At the current time, we're typically either doing a reinduction course with BCG or going into things like intravesical chemotherapy. So this is a study that's looking at a novel agent, which is cretostimogene, in those that are BCG-exposed.
Zachary Klaassen: Fantastic journey. Thanks so much for that overview. I think when we look at the BCG-unresponsive, we had great results at SUO 2024 as well for BOND-003, updated complete response rates. So this is clearly working in that BCG-unresponsive. And certainly the BCG-exposed is another unmet need, and particularly the papillary-only. We see a lot of these patients. Just talk about the importance of this sort of side arm of that Cohort B and what we hope to learn in the papillary-only patients.
Trinity Bivalacqua: Yeah, so I think you bring up an important point because when you look at all of the trials in the BCG-unresponsive space, those patients that had papillary-only disease actually did better, had better response rates. And I think that the reason why that's the case is because, in a lot of ways, a papillary-only patient, who has only papillary disease in their bladder, we as the urologists and the surgeon, it's our job to do a good resection and to clear that bladder.
And then we're giving an adjuvant therapy, which is then going to help, hopefully, prevent recurrence and/or progression. So I think when you have a novel agent like creto, which works via a dual mechanism, both the immune system as well as in RB-altered tumors, I think what we're seeing, and what I suspect we're going to see, just like we saw in the BCG-unresponsive space, is probably good duration of response and high response rates.
And I think that that's what we're looking for in our patients, especially in the area of BCG shortage, where we don't want to go back to BCG because we don't have BCG available, and we don't want to reduce the dose. So if we had an agent that was highly effective in this disease space, I think it would greatly impact our patients' quality of life and, more importantly, their bladder cancer treatment.
Zachary Klaassen: Yeah, absolutely. Great answer. I know it's early in the CORE-008 accrual, but maybe just give us a highlight of how many sites we're expecting, how many patients enrolled, when we really see this ramping up, when we may expect some early data from Cohort B.
Trinity Bivalacqua: Yeah, we're going to have greater than 10 sites that are available. They're throughout. They're academic sites. They're large urology group practices, VA sites. And the purpose of this is to have a diverse group of patients as well as a diverse group of practitioners.
I think, sometimes, when you look at trials, you want to be able to say that you want to be able to mimic what's happening in the real world because, sometimes, trial results don't translate into clinical practice. So what we've tried to do intentionally is have a diverse group of practitioners, providers, oncologists that are treating patients, and have it throughout the country so we have multiple areas.
I think what all trials are trying to do today is to look at more patients that have different races, sexes, in order for us to look at diversity. That's super important when we try to look at the effectiveness of a novel agent. And that's honestly one of the intentions of this trial.
Zachary Klaassen: Wonderful. Trinity, thanks so much for the update on CORE-008 Cohort B. Always appreciate your time and expertise on UroToday.
Trinity Bivalacqua: Thanks, Zach.
Zachary Klaassen: Hello, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia, delighted to be joined on UroToday by Doctor Trinity Bivalacqua, urologic oncologist from the University of Pennsylvania. Today we're going to be discussing an SUO 2024 presentation, looking at the trial design for CORE-008, specifically Cohort B, looking at the impact of cretostimogene in BCG-exposed patients.Trinity, thanks so much for joining us on UroToday.
Trinity Bivalacqua: Thanks, Zach. Appreciate you having me here today. I'd like to talk a little bit about the phase 2 multi-cohort multicenter trial looking at the effects of cretostimogene in patients with high-risk non-muscle invasive bladder cancer.I'd like to talk a little bit about Cohort B, which is a trial looking at the effects of cretostimogene in patients that are termed BCG-exposed. These are patients that do not meet the BCG-unresponsive definition but do have recurrent disease which is high-grade.
In the Cohort B study, these are patients that will have CIS or papillary-only disease. So you could have only CIS or just high-grade papillary disease only. And they will undergo typical treatment with an induction course of cretostimogene weekly for 6 weeks and then a maintenance course weekly, per the SWOG protocol. This is identical to that of previous phase II trials in which creto was tested in patients with BCG-unresponsive disease.
The endpoints are those that are a complete response, a duration of response, recurrence-free survival, and cystectomy-free survival. Now, this is a disease space that we are currently looking at multiple different treatment options. At the current time, we're typically either doing a reinduction course with BCG or going into things like intravesical chemotherapy. So this is a study that's looking at a novel agent, which is cretostimogene, in those that are BCG-exposed.
Zachary Klaassen: Fantastic journey. Thanks so much for that overview. I think when we look at the BCG-unresponsive, we had great results at SUO 2024 as well for BOND-003, updated complete response rates. So this is clearly working in that BCG-unresponsive. And certainly the BCG-exposed is another unmet need, and particularly the papillary-only. We see a lot of these patients. Just talk about the importance of this sort of side arm of that Cohort B and what we hope to learn in the papillary-only patients.
Trinity Bivalacqua: Yeah, so I think you bring up an important point because when you look at all of the trials in the BCG-unresponsive space, those patients that had papillary-only disease actually did better, had better response rates. And I think that the reason why that's the case is because, in a lot of ways, a papillary-only patient, who has only papillary disease in their bladder, we as the urologists and the surgeon, it's our job to do a good resection and to clear that bladder.
And then we're giving an adjuvant therapy, which is then going to help, hopefully, prevent recurrence and/or progression. So I think when you have a novel agent like creto, which works via a dual mechanism, both the immune system as well as in RB-altered tumors, I think what we're seeing, and what I suspect we're going to see, just like we saw in the BCG-unresponsive space, is probably good duration of response and high response rates.
And I think that that's what we're looking for in our patients, especially in the area of BCG shortage, where we don't want to go back to BCG because we don't have BCG available, and we don't want to reduce the dose. So if we had an agent that was highly effective in this disease space, I think it would greatly impact our patients' quality of life and, more importantly, their bladder cancer treatment.
Zachary Klaassen: Yeah, absolutely. Great answer. I know it's early in the CORE-008 accrual, but maybe just give us a highlight of how many sites we're expecting, how many patients enrolled, when we really see this ramping up, when we may expect some early data from Cohort B.
Trinity Bivalacqua: Yeah, we're going to have greater than 10 sites that are available. They're throughout. They're academic sites. They're large urology group practices, VA sites. And the purpose of this is to have a diverse group of patients as well as a diverse group of practitioners.
I think, sometimes, when you look at trials, you want to be able to say that you want to be able to mimic what's happening in the real world because, sometimes, trial results don't translate into clinical practice. So what we've tried to do intentionally is have a diverse group of practitioners, providers, oncologists that are treating patients, and have it throughout the country so we have multiple areas.
I think what all trials are trying to do today is to look at more patients that have different races, sexes, in order for us to look at diversity. That's super important when we try to look at the effectiveness of a novel agent. And that's honestly one of the intentions of this trial.
Zachary Klaassen: Wonderful. Trinity, thanks so much for the update on CORE-008 Cohort B. Always appreciate your time and expertise on UroToday.
Trinity Bivalacqua: Thanks, Zach.