Aaron Berger: My pleasure. Thank you.
Ashish Kamat: If you could, tell the audience a little bit, obviously about what's being presented, but the thought process behind the combination of CG and Gem. Share with us a little bit the mechanism and the mechanistic rationale.
Aaron Berger: There's a couple studies out there regarding cretostimogene intravesically along with systemic immunotherapy that had some synergies. And then there was some preclinical work showing there may be a synergistic effect with cretostimogene with intravesical gemcitabine.
So that's how the thought came about of using these two in combination. So that was the genesis of the CX arm of this trial. I was trying to see if the combination with potentially synergistic mechanism of action might be better than cretostimogene alone.
Ashish Kamat: Yeah, no, because people will sometimes say, "Oh no, everyone's trying everything with everything." But it's important to recognize that there was preliminary work done and something to do with the metronomic dosing of gemcitabine.
Aaron Berger: Yes.
Ashish Kamat: And then if you could share with the audience what was presented and what the data shows.
Aaron Berger: Sure. So in the CX arm that was presented here, they had about 55 patients that was both BCG-exposed and BCG-unresponsive with CIS and high-grade papillary disease.
And basically what they showed in the overall intent-to-treat population, they had very impressive event-free survival, upwards of 90%, which is some of the highest numbers we've seen in this patient population.
Now that was a combination of CIS and papillary-only. But even in their CIS cohort, complete response rate was in the high 80s. So, I think, those numbers are certainly very impressive. It's early. It's early data, but I think it's a very positive outcome so far and needs a little longer followup.
And this was a small study, obviously small numbers of patients. But moving forward, I think that combination really seems to be something to continue moving forward with. I think based on this, I know there's a SWOG trial they're looking at starting up to explore this concept of combination therapy further.
And the other, I think, really positive thing to come out of this was it appears that the, because they did the gemcitabine combination both either concurrently, so every treatment with cretostimogene or sequentially where they got two doses of creto followed by gem.
And the sequential one was basically equivalent as far as efficacy, but on the toxicity side was improved as you may expect. I mean, there's just les treatment, there's less doses of gemcitabine and patients tolerated it well. No one dropped out of the trial for side effects in that arm.
So, I think, anytime we can have better efficacy with less burden on the patient's bladder and also less burden on clinical staff and get people in and out of the clinic faster is definitely a win.
So certainly based on the early numbers, were small numbers, but the early data is pretty impressive I think with the cretostimogene and gemcitabine combination.
Ashish Kamat: Yeah. I mean, again, obviously the caveats are small numbers, but I think the track record of the creto platform has been good enough that we suspect, or at least most of us think that these small numbers, even when they expand, the efficacy might or should stay fairly stable.
Because otherwise you see those with newer drugs that come out that sometimes you get great results with five, 10 patients and you open up a bigger trial and those numbers drop.
Aaron Berger: Yes, certainly.
Ashish Kamat: What was encouraging also was the toxicity data, right? The dropout. But you mentioned a little bit about your... And I want to probe a little bit and get your opinion. With so many combinations being studied with the CG creto backbone per se, what's your sense as to which one will be the ultimate winner from your perspective?
Aaron Berger: Well, I mean, I think if there's monotherapy that's as effective, and obviously that's the easiest to just dose one drug and move on. But certainly from this cohort of patients, it seems there may be some synergistic effect with the combination with gemcitabine.
So I don't think from a busy, independent practitioner like myself and larger group practices, I don't think it's a barrier this combination. I think it's pretty easy to dose drugs that we're familiar with. A lot of us use intravesical gemcitabine monotherapy already.
A lot of independent groups don't necessarily do Gem-Doce that often, just it's a little bit more complicated, it takes more time, but I think this is relatively easy to do. So in terms of monotherapy versus in combination, I guess the jury is out long term is where that will land.
Certainly the BOND-003 data is going to be published soon in the monotherapy space, so I guess time will tell. But certainly if there's some even better results, you're getting upwards of 90% event-free survival data like in the CX trial. I mean, those are pretty impressive numbers.
I mean, we really haven't seen numbers that high with any of the novel agents in bladder cancer yet.
Ashish Kamat: Yeah. I think it's a great time for our patients because a lot of choices, a lot of drugs that are not available and different mechanisms of action and we hope, of course, that CG gets approved.
Let me ask you a little bit, and this is a little bit off topic, but since you brought it up, I do want to ask you. I hear this from my community colleagues all the time, because sitting in academia, we and the guidelines all say Gem-Doce, Gem-Doce, use Gem-Doce for all the reasons including cost-effectiveness-
Aaron Berger: Sure.
Ashish Kamat: ... so on and so forth. But I hear from my community friends and colleagues that it is really cumbersome for the practice.
Now, if you had this combination of CG plus gem, would you find that less, you said you'd find that less cumbersome, but share with our audience a little bit that might be listening in as to why and how that would be less cumbersome than say doing combination therapy.
Aaron Berger: Yeah. Well, I mean, I think it's from a toxicity standpoint, I think, this data showing the sequential at least very well-tolerated. So, I think, that may have better tolerability than the Gem-Doce protocol.
And also most people, I hear various ranges of how long people are in the clinic with Gem-Doce. Some people are there for the entire duration. Some people, they do gemcitabine and then they do Doce, and then they leave and they don't have to stay in the clinic the whole time.
So, I think, there's different ways you can go about it, but I think, in this combination where you're doing the cretostimogene, draining that out and then you're really only doing, assuming the sequential is where we end up going, you're just doing one agent.
I mean, that's very easy. Don't need to stick around in the office because, I think, that's really the problem. When you have two different drugs, which is why I was very encouraged to see that the sequential was basically as good. Because even in a trial setting, having patients there for a couple hours, my parking lot gets very full.
So to have them have one agent, drain that out, do another agent, drain that out, just having one and out the door, that just makes it so much easier for all of us.
So if you get the same benefit from combination therapy in a sequential fashion, I think that's a huge win for busy community practices.
Ashish Kamat: And for the patients too, right?
Aaron Berger: Yeah, 100%.
Ashish Kamat: Because patients don't want to stick around in our offices longer than they have to-
Aaron Berger: No, that's right.
Ashish Kamat: ... so, I think, it's a win not only from our side, but also the patient's side. It's a win-win all around.
Aaron Berger: Yeah. And to your earlier point, I mean, I think it's a great option for patients. I mean, all these new novel agents are great and if you're trying to ultimately have cystectomy-free patients, you can potentially go from one agent, to another agent, to another agent.
So any additional treatments we have that come into market and those we already have, it's come a long way in the last several years. So very encouraging for patients, 100%.
Ashish Kamat: Absolutely. Absolutely. Thank you for taking the time. Been a pleasure.
Aaron Berger: Pleasure. Thank you very much.