Trinity Bivalacqua: Sure. Thanks, Sam, for having me and giving me the opportunity to discuss it. So the CORE-008 trial is a multi-cohort trial, so has different disease states. We've got efficacy or looking at different medications or therapeutics in the BCG-naive space as well as BCG-unresponsive. But what I'm presenting at the SUO tomorrow is actually the cohort CX.
So CX is where we took patients with BCG-unresponsive CIS or BCG-exposed population. So it's got two disease spaces in it and we're looking at the effects of a combination therapy of cretostimogene combined with gemcitabine. So it essentially has two arms. The two arms look at concurrent treatment with creto with gem or sequential. So sequential means that they get creto for the first two weeks and then on the third week get gemcitabine, two weeks of creto, six week gemcitabine. And then in the maintenance phase, they also get two of creto and then gemcitabine.
Sam Chang: Interesting.
Trinity Bivalacqua: Or they get it all at the same time.
Sam Chang: Right. With a single instillation?
Trinity Bivalacqua: With one single instillation. Obviously multiple passes, but nonetheless it's given concurrently.
Sam Chang: Okay.
Trinity Bivalacqua: And the thought was is this going to have a synergistic effect? Will it have an additive effect? Will patients tolerate this?
Sam Chang: Yes.
Trinity Bivalacqua: I mean, as you know, treating patients with intravesical treatments can be challenging at times.
Sam Chang: Right, right. And so tell us, I know this is the early round of evaluating these patients. So tell us some of the findings that are really important.
Trinity Bivalacqua: Yeah. So I mean, it's a phase-two trial. So we're looking at 55 patients in the entire cohort. The majority of these patients have CIS. Actually we have got patients with T1 as well as TA disease. And remember, because it's BCG-unresponsive and BCG-exposed, it really is a heterogeneous group.
Sam Chang: Very real world.
Trinity Bivalacqua: Real world.
Sam Chang: Absolutely. Yeah.
Trinity Bivalacqua: And to that point, the majority of people that are actually investigators in this trial, it was sponsored by the SUO or partnered with the SUO CTC are actually from community-based practice. So 80% of the urologists participating in this trial are from community-based practice. So it's not really an academic-led trial.
Sam Chang: Right.
Trinity Bivalacqua: And what the data showed was is that number one, in both of these disease spaces, 65% of the patients enrolled in the trial were BCG-exposed. In both of these disease spaces, if you look at all comers, all of them, the complete response rate at three months was 95% and at six months was 89.5%, right? So 90%. So what this is demonstrating is that we see nice, complete response rates at three and six months. Now, as you pointed out, early coming, this is early data. And I think what it demonstrates is that you do see a pretty robust response. Now what we are not able to determine at this time is is there really an additive versus synergistic response? And that's something that we're going to see when the data matures over time.
Sam Chang: Sure. Over time. Yeah. And what about the side effect profile?
Trinity Bivalacqua: Yeah.
Sam Chang: You mentioned perhaps the difficulty with these patients because they were at least BCG-exposed or maybe BCG-unresponsive. So tell me kind of what the early kind of read is on those.
Trinity Bivalacqua: Yeah. And I think that's the most, I think probably the take-home from the results is that, well, first of all, it was tolerated, very well-tolerated, especially in the arm that had sequential. So patients, there were no dropouts, serious adverse events didn't exist, just like the BOND-003 trial, just like the previous trials. But what we did see in those patients that got concurrent, we did see four patients drop out because of just irritation. Now not serious adverse events, they just didn't tolerate it as well.
Sam Chang: Right. In terms of lower urinary tract symptoms?
Trinity Bivalacqua: Lower urinary tract symptoms and with just sort of the normal stuff, frequency, dysuria, where they weren't able to tolerate the combination at the same time.
Sam Chang: The combination. This kind of feeds into some of the work that Eugene Pietzak's done at Memorial, others looking at this combination of, okay, you have a cytotoxic effect, then you simulate the immune system. It all kind of makes sense and the idea that sequential therapy with a single drug, so in other words, not having to combine chemotherapy, et cetera, but that you will see if it has a synergistic effect, but obviously it makes sense it's tolerated. We've given single-agent gemcitabine for a long, long time. We're doing more of the double therapy, but clearly the single agent is tolerated. We give it perioperative. I mean, in terms of safety and at least in our experience with the clinical trials, cretostimogene is very well-tolerated.
So the idea that you have a combination of therapeutic, it makes sense. You've got a cytotoxic and you've got an immunostimulant. So tell me, have we finished enrolling in that CX cohort or are we still enrolling patients? Tell me about overall looking at CORE-008, because it's a multi-arm kind of study. So where are we at?
Trinity Bivalacqua: Yeah. So for cohort CX, we finished enrollment. We're now looking, obviously just waiting for patients to ... They're getting their maintenance, seeing the efficacy. Obviously for me, the way I look at a clinical trial in a non-muscle invasive bladder cancer is what is the efficacy at 24 months?
Sam Chang: Sure.
Trinity Bivalacqua: I mean, for me, that's what I want to tell my patient and I'm sure you feel the same way. Do you tolerate the drug? Is it safe and is it durable? So we love to talk about these early results, the 12 months and 24 months. And I think one of the advantages of creto is that you see durability of response and that's what was shown in BOND-003 three, which is looking at creto in the BCG-unresponsive space as a monotherapy.
I think the other thing that I think is worth discussing is that, didn't matter if you got sequential or concurrent, the efficacy rate was similar. So we didn't see a drop-off in efficacy, we didn't see an improvement in efficacy, at least at the early time point. So I think that's another important point as you highlighted that what goes on with cytotoxic and an immunotherapeutic or activating that host immune response, I think we need to wait for the final results and maturity.
Sam Chang: And tell me, remind me again, in the CX arm, maintenance was what type of regimen?
Trinity Bivalacqua: Yeah. So the same, maintenance as you saw in all of the previous, the BOND-003 trial, you're looking at three, six, 12, essentially the SWOG protocol, as you know. The other thing that we didn't talk about, but I think to make the point in this trial we allow for reinduction if the patient had a high-grade TA or CIS at their first assessment at three months. So this does allow for reinduction.
Sam Chang: I know it's early, but did you see some rescue in those patients?
Trinity Bivalacqua: Yeah. So there's only been a handful of those patients that are there.
Sam Chang: Handful of those patients. Yeah. Hard to say. Yeah.
Trinity Bivalacqua: So I don't think we can make any determination there.
Sam Chang: Yeah, I think for sure you know in all honesty, it's going to be probably tolerated, that. And then clearly I would guess, a pure conjecture, that a subset's going to respond to that additional therapy induction. So very exciting work, Trinity. I think the paradigm of how we treat is going to be a combination of who we escalate, who we de-escalate, who we maintain maintenance, et cetera, all those things, but really further verifying the possible beneficial role of chemo plus an immunostimulant is very, very exciting. So huge applause to you and your help in terms of helping to guide this whole kind of CORE-008 because it's got multiple arms but very exciting and thanks for spending some time with us, very much so.
Trinity Bivalacqua: Thanks, Sam. I really appreciate it. And as you said, this is a team effort. We've got all the investigators that are enrolling their patients and we're so appreciative of everything everybody's doing.