Taigo Kato: Yes.
Pedro Barata: ... urologist from Osaka Institution out of Japan. So, thank you so much for joining us today.
Taigo Kato: Yes, me too. My pleasure.
Pedro Barata: And I want to congratulate you.
Taigo Kato: Thank you.
Pedro Barata: Great work around minimal residual disease in kidney cancer.
Taigo Kato: Yeah, right.
Pedro Barata: So, your study is, in my opinion, a very important study in RCC. We do see an emergence of minimal residual disease methodologies, ways to go after the evidence of recurrence or micrometastatic disease or minimal residual disease. And you can do it in different ways, right?
Taigo Kato: Mm-hmm.
Pedro Barata: So, perhaps, before I ask you for you to summarize the findings with us, but what made you embark on this longitudinal evaluation of baseline and post-radical nephrectomy for your cohort of patients with renal cell carcinoma?
Taigo Kato: So, as you may know, so far, we have not detected our ctDNA of breath samples, because basically, kidney cancer is known as a low-shedding tumor. So far, transitional whole-exome sequence could not detect enough number of variants in renal cell carcinoma. That's why we modified, we changed the platform to use the whole-genome sequencing MRD protocol.
Pedro Barata: Gotcha.
Taigo Kato: Yes.
Pedro Barata: So, you're basically going after detecting with more sensitivity, if you will-
Taigo Kato: Yes.
Pedro Barata: ... minimal residual disease.
Taigo Kato: Yes. That's right, that's correct.
Pedro Barata: Can you tell us where you finally... Explain, a little bit, how you did the study, because you are collecting blood at different time points-
Taigo Kato: Yeah, that's right.
Pedro Barata: ... and you did that over a cohort of patients treated at your institution. Can you walk us through how you did it and what you found?
Taigo Kato: Okay. So, origin sequencing, we specifically applied this origin sequence uploads, because we can create personalized ctDNA panel generated from origin sequence data. So incorporating up to 1,000 tumor-specific variants. So we can detect 100% possibility at the baseline and 81.1% at one month after surgery.
Pedro Barata: So you're basically describing a tumor-informed test.
Taigo Kato: Yes.
Pedro Barata: Right?
Taigo Kato: Tumor-informed.
Pedro Barata: Which we do have some as well commercially available here.
Taigo Kato: Yeah. Yeah.
Pedro Barata: And what's interesting to me, so you go from 100% at baseline, meaning primary tumor mass present, and it drops to less than 15%, as you said, 10, 12% or so, post-nephrectomy.
Taigo Kato: Yeah, post-nephrectomy, yes.
Pedro Barata: Right. And then you're also reporting clinical outcomes in terms of recurrence, right? I believe your patients did well.
Taigo Kato: Yeah.
Pedro Barata: What do you think about 10 to 12%? I'm thinking, because you include stage one to stage four, I believe, I would think that number could potentially be higher, but what are your thoughts about it? Is that true? Is that what you're expecting to see? About 1 out of 10 patients with detected ctDNA? What are your thoughts?
Taigo Kato: I see. So 11.1% of positivity at one month after surgery, yes, we expect that kind of data, because we enrolled around 30 patients, but 80% of patients was pathological T3 or T4.
Pedro Barata: Okay.
Taigo Kato: Yes. So it's clinically thinking, yes, it number reflects real-world settings right now. So 11.1% is reasonable, I think.
Pedro Barata: Gotcha.
Taigo Kato: Yes.
Pedro Barata: Okay. So do you think moving forward, I guess, maybe I'll ask you what the next steps are for your study, and how close are we, or how far are we-
Taigo Kato: I see.
Pedro Barata: ... to use an assay like this, a tumor-informed assay, or perhaps a tumor-non-informed assay, to help us select the patients who are destined to recur? Therefore identifying those that might benefit from immunotherapy-based strategies.
Taigo Kato: Yes, that's right. I think it's very nice question. So we always use adjuvant pembrolizumab after resection surgery for high-risk patient, right?
Pedro Barata: Yes.
Taigo Kato: But sometimes I think in my opinion, so not all patients needs that kind of adjuvant pembrolizumab. Because yes, so some kind of patients are experienced immuno-related adverse events afterwards. In our study, we want to stratify the patient who needs pembrolizumab, who doesn't need pembrolizumab in the near future. So I think ctDNA-guided therapy. In other words, MRD-guided therapy is useful to stratify the patient. So that's why now we are collecting that kind of data right now. So far, we have collected around 40 patients in total. And in our project, we will collect up to a number of 50 patients. So I think after that, we can stratify the patient who needs pembrolizumab or who doesn't need pembrolizumab. And we will validate that kind of our findings using another validation data. So in the near future, in a few years, I think. Yes.
Pedro Barata: I see. So one last question before letting you go. Of all the tests out there, it is tumor-informed, tumor-uninformed, urine-based test, Metacyte, et cetera, or even KIM-1, et cetera.
Taigo Kato: Yes. Yes.
Pedro Barata: How do you see this field moving? What do you think if you were to bet, what are the winners? What would you say? What are your thoughts?
Taigo Kato: I see. It's also very nice question. So as you say, now KIM-1 is a very nice, very good prognostic marker for systemic therapies basically. So I think in the near future, we will combine the ctDNA plus, for example, KIM-1 or AKT, or metastasis recurrence afterwards. Maybe just not one parameter, but two parameters has better our accuracy to predict the recurrence afterwards. So I think not only one parameter, so just we want to combine that kind of useful biomarker.
Pedro Barata: Right. I agree with you. And as we see an emergence of novel strategies and Phase III trials reading out including-
Taigo Kato: Yeah, that's right.
Pedro Barata: We just heard data from LITESPARK-022.
Taigo Kato: Right. Right. Right.
Pedro Barata: Data from RAMPART-
Taigo Kato: Yes.
Pedro Barata: ... et cetera.
Taigo Kato: Yeah.
Pedro Barata: I do anticipate this field to continue to grow.
Taigo Kato: Yes.
Pedro Barata: Right? And hopefully we'll get a sense to how to better select those patients, to your point that actually truly benefit from treatment with the hopes of preventing recurrences.
Taigo Kato: Yes, right.
Pedro Barata: Or in other words, to cure, right?
Taigo Kato: Yes. Right, right, right.
Pedro Barata: So thank you so much Dr. Kato for joining us today and congratulations.
Taigo Kato: My pleasure. Thank you so much.
Pedro Barata: Thank you.