Juan Ruiz-Bañobre: Thank you very much for this opportunity to be here pretending my work after presenting in the meeting.
Zachary Klaassen: We're very excited to talk to you about this because really, we've heard a lot about ctDNA, urothelial carcinoma, obviously with IMvigor011, but we're talking about early detection in RCC, which has typically not been associated with any ctDNA work that I'm aware of. So just, what's the landscape look like for ctDNA in RCC?
Juan Ruiz-Bañobre: Yeah, RCC is a very challenging scenario for ctDNA analysis because it's a very low shedding tumor. Even when this tumor is very, very well vascularized. So I think that we have to understand why, which is the biology behind this low shedding setting.
Zachary Klaassen: Yeah, absolutely. Just take a minute to tell our listeners about your study design, why you looked at ultra sensitive ctDNA for this study.
Juan Ruiz-Bañobre: Yes. I think the first point is that based on this low shedding scenario, we need a very ultra sensitive test because other tests with a lower sensitivity probably are not going to detect ctDNA in this tumor type. So what we did was a retrospective analysis of prospectively collected plasma samples, serial plasma samples. We collect samples at base lay, at week six, and week 12, then, and a schedule follow-up samples and at progressive disease in a cohort of advanced renal cell carcinoma treatment naive patients. These patients were mainly treated with nivolumab/pembrolizumab, and some patients, around nine patients, with tyrosine kinase inhibitors. In total, we analyzed 37 patients.
Zachary Klaassen: Excellent. And you've got some really interesting results. Maybe just highlight the key results for our listeners from the work you presented.
Juan Ruiz-Bañobre: Yes. We use a tumor informed whole genome as sequencing based assay, the next personal. So what we found was that the detection rate was 84% and this detection rate was prognostic in wrestling when we categorized with ultra-high ctDNA levels and not ultra-high ctDNA levels. But also, we analyzed the clearance of ctDNA and we found that the molecular complete response was prognostic for progressive free survival and from overall survival.
In addition, we only saw that the molecular complete response was associated with the best overall response. It was predictive for disease control. And those patients who achieve a molecular complete response, even in the stable disease by resist, they achieve a very good survival results.
Zachary Klaassen: Excellent. So this is early work. It's very exciting. You're getting overall survival, progression-free survival response signals, as well. Where do we go from here? I mean, if somebody treats a lot of kidney cancer, I find this very exciting because we may have a marker in early days that could help us prognosticate these patients.
Juan Ruiz-Bañobre: Yeah. I think the first step is to understand well, the biology behind these results. Because we found, for example, that there was a very high correlation with IMDC score. We also found a good correlation with the histological high-risk features and with stage diagnosis. And the most important, we found a correlation with the prior nephrectomy just or not. Those patients without the kidney, the tumor inside has very low ctDNA levels. So this is the first step. And then I think that we need to validate our results in advanced setting.
Zachary Klaassen: Sure.
Juan Ruiz-Bañobre: And then try to move to the early stage setting in the adjuvant setting because I think that these techniques can be very useful to help in the escalation or deescalation of therapies to maybe deliver to the clinic on off strategies of therapy. Maybe we can avoid the therapy during some time. And also, we have to validate the clinical utility of these techniques. I think that not only in renal carcinoma setting, but it's very important to analyze prospectively collected cohorts from clinical trial, and also conduct clinical trials in a prospective manner.
Zachary Klaassen: That's a great answer. I think I love this signal in early adjuvant because we've seen pembrolizumab have a survival advantage in an adjuvant setting. Pembrolizumab plus belzutifan now. So the question is with ctDNA, should we give them double or Should we give them pembro by itself, or should we just observe these patients? So I think that's some really interesting work to give us something to go forward with.
I know it's a super busy meeting, Juan. Thank you for joining us UroToday. Any concluding remarks for our listeners before we wrap up?
Juan Ruiz-Bañobre: Yes. As a conclusion, I can say that what we know with renal cell carcinoma is low shedding tumor. This is a very challenging scenario. Medical oncologists and international scientists had a challenge ahead that we have to solve. Technology is important, very important, but also we have to work in the clinical utility and how to implement in the clinic to think in the strategies, how we are going to treat patients. Probably we have to integrate different omics, not only ctDNA, but also maybe gene expression, or maybe methylation, or even some different molecular specs like proteomics.
Zachary Klaassen: Sure.
Juan Ruiz-Bañobre: So the future is there and it's challenging.
Zachary Klaassen: That's great. Thanks so much for joining us, Juan.
Juan Ruiz-Bañobre: Thank you.