Chiara Mercinelli: Thank you very much for the invite.
Ashish Kamat: Of course. Now, you've been doing a lot of work in bladder cancer in general, of course, with the IBCG, with the Milan San Raffaele, endeavors that we have. Here at GU26, you have a poster that's very interesting, looking at MTAP loss and liquid biopsies. Share with us the poster a little bit.
Chiara Mercinelli: Yes. We know that now the research is moving quite fast in the bladder cancer field. There are a lot of new novel biomarkers that could emerge and could be the new targets for novel therapies. MTAP loss is one of them. There's a limitation about tumor tissue biopsy in all the oncology field, which is that sometimes we don't have enough tissue to perform a proper analysis. We try to find if also with liquid biopsy, we have a good detection rate of MTAP loss. In fact, if we have enough tumor fraction of at least 10, 20%, we can find a percentage of MTAP loss which is similar to the tissue one. We know it's between 20 and 30%.
Ashish Kamat: Liquid biopsies opened up a whole different avenue now where we don't necessarily, if it is proven, have to rely on invasive biopsies on patients. You and your group, of course, have done a lot of work, including with the foundation medicine dataset. In general, what's your idea as to where the liquid biopsy field is heading in bladder cancer?
Chiara Mercinelli: The most important field probably by now is for the localized disease, in particular, to try to decide when and how to treat the patients. I'm speaking about bladder preservation strategies in patients who maybe have negative DNA, or speaking about intensification therapy in patients who have a ctDNA positive. Also when we look at the novel strategies in the localized disease, we always have these perioperative design of the trials. But maybe some patients do not necessarily need also the adjuvant part, but we don't know which patients need what.
Ashish Kamat: Right. Of course, we've focused on tumor-informed ctDNA to date. But data such as yours where you can actually look at the liquid biopsy and detect alterations, pathways, et cetera, do you think that's going to open up an avenue of more targeted therapies? How do you think you would use, for example, your data? How would you use that in the clinic?
Chiara Mercinelli: Well, in particular about MTAP plus, we know it's quite early alteration in the process of the tumorigenesis in bladder cancer. Probably we can detect it in any phase of the history of the patients, but there are some other alterations that could emerge after receiving the different treatments. It could be useful to have easy access to tumor DNA of the patients before each line of therapy for the metastatic setting, for example, in order to guide and really inform the treatment decision every single time.
Ashish Kamat: Right, and I think that's important. That's the benefit of the liquid biopsy, right? You can do it at all times. Remind me, in your poster, was this a serial collection? Was it a one-time snapshot?
Chiara Mercinelli: No, this was absolutely only informative. It just was a one-time collection. We just wanted to understand if the detection rate is similar to the reality that we face with the tumor tissue.
Ashish Kamat: Sure, and what platform did you use?
Chiara Mercinelli: We used both for the tumor tissues biopsies and liquid biopsies the NGS from FoundationOne. It was the FoundationOne CDX for the tissue and FoundationOne CDX liquid for liquid biopsies.
Ashish Kamat: Yeah, and there's a lot of good work coming out of the FoundationOne with obviously our partnership with Jeff Ross and that all group. I mean, it's a lot of stuff happening at this ASCO. What else are you working on when it comes to liquid biopsies? What's the next thing that you're going to be doing?
Chiara Mercinelli: We conduct a lot of different trials in neoadjuvant setting in Milan. Our focus now is try to study all the patients with ctDNA before and after the neoadjuvant treatment in order to try to identify those patients who can be candidate to bladder sparing in combination with MRI cystoscopy. It's a whole teamwork.
Ashish Kamat: Great. If I had to ask you specifically, what's the one thing when it comes to liquid biopsies that you're most excited about?
Chiara Mercinelli: Oh, there are so many. Let me say the non-invasiveness. It's easy for the patient. It's not like a torture that we have to give to the patients every single time. Also, if we use a tissue for the liquid biopsies, we have plenty of information to study them.
Ashish Kamat: Yeah, I think patients like that, right? Because yes, it is a blood draw, but it's non-invasive. You don't have to rely on archived tissue. I really think this has opened up a whole new avenue for us to not only look at patients, but their disease. Data such as yours, and of course the data from IMvigor and the NIAGARA that we're going to be seeing here, is really going to be very informative. Chiara, thank you so much for taking the time. Always a pleasure.
Chiara Mercinelli: Thank you.