Pedro Barata: Hello and welcome. My name is Pedro Barata. I'm a GU medical oncologist and an associate professor of medicine at Tulane Medical School in New Orleans, Louisiana. It's my true pleasure to be joined today by Dr. Laurence Albiges. She's really well-known and a star in the kidney clinical arena. She's an MD/PhD medical oncologist, and currently the head of the Medical Oncology Department at Gustave Roussy in Villejuif, France. So welcome, Dr. Albiges. Thank you so much for taking the time to be with us today.

Laurence Albiges: Thank you, Pedro. Thank you for the invitation.

Pedro Barata: Absolutely. By the way, I start by congratulating you for your fantastic talk and presentation of a very important study, your phase 2 Keynote-B61 that basically explore the combination of lenvatinib with pembrolizumab as first-line treatment for patients with non-clear cell renal cell carcinoma. So again, very elegant presentation, and I was hoping we could talk a little bit about that today if that's okay with you.

Laurence Albiges: Sure. That will be my pleasure. So actually, this is a phase 2 in an area that is clearly an unmet need. Namely, what we call non-clear cell renal cell carcinoma that should not be named as such because these are different entities that are usually having a worse prognosis than clear cell, and that are really challenging to treat. And so what we've been reporting this time, and it's the first time we're presenting the data, is a phase 2, a non-randomized phase 2, that enroll patient with non-clear cell histology that never been previously treated and that were treated with a combination of pembrolizumab administered every six weeks with lenvatinib at 20 milligrams per day. So it's a combination of VEGF TKI, lenvatinib, plus immune checkpoint pembrolizumab. The primary endpoint of this study is response rate.

Pedro Barata: Fantastic. Thank you so much. And so remind us, as you were saying, which you raise a very, very good point, right? Non-clear cell behaves differently from clear cell. And we can actually go further and argue that actually within non-clear cell group, there's many different diseases that are part of these broad classification of non-clear cell. Can you remind us what type of patients were enrolled in these phase two, as far as histology goes, and then go ahead also and give us kind of the highlights, if you will, on the efficacy portion of this study.

Laurence Albiges: Sure. So that study is about a 150-patient study. What has been presented at this ESMO are the very first results with an efficacy population of 82 patient. These were patient for which we had sufficient follow-up. And with regard to your question of histology, the vast majority of those patients are papillary nccRCC carcinoma. They account for 51 patient in the efficacy population. So that's about 62% of patient. The second most frequent entity are what we call chromophobia RCC, and we know those patients are hard to treat because they tend to be less sensitive or less responding to an immune checkpoint when used as single agent. And then we had other histologies, such as translocation RCC or unclassified tumors, or even more rare tumors, such as medullary carcinoma. So these are, as you can see, a very [inaudible] patient population.

Laurence Albiges: What are the key results? Well, first, the response rate, that is achieving 47.6%. So almost one patient out of two that has objective response. The disease control rate, that is 79%. So basically, almost 80% of patient that has either partial response or stable disease or even complete response. And if you look at the response by histology [inaudible], it's very consistent across papillary and classified translocation and other tumor type. The histology where we saw the less responsive were it chromophobe tumor, as anticipated. And I think, at this point, it's important to stress that we already had data with pembrolizumab single agents that were previously reported by David McDermot. We had seen other regimen with combination with VEGF TKI, and this is the first report of lenvatinib, plus pembrolizumab in this histology of patient with non-clear cell. There was no significant signal in terms of safety. This is the regimen that we are used to handle.

Laurence Albiges: And so, therefore, there was no new safety signal. I think it's important that out of the 82 patient that were accessible for response, we could see some degree of tumor shrinkage in the vast majority of them. It was 86% of patient that had some degree of tumor shrinkage. So clearly, a combination that is active, for now, the follow-up is short. We only had 8.2 months follow-up. Nevertheless, many patients were still under treatment at the time of analysis. Therefore, we will be waiting for further follow-up and the entire patient population to be followed, to provide final analysis.

Pedro Barata: No, it is so important as you mentioned and summarized these results. It's very good news, in my opinion, promising results for patients with non-clear cell histologies. And so thank you for highlighting it so elegantly for us. And as you mentioned, so now we have data with lenvatinib, pembrolizumab. There are other combos being explored out there with proof of concept and promising results. So can you tell us what the next steps for these efforts seem to be? I mean, sounds like you're going to update with longer, with more mature follow-up, you're going to update those results and hopefully we'll see the data being consistent over time. Is any other perspectives you can share with the audience as far as next steps for the non-clear cell RCC patients?

Laurence Albiges: Yeah. Thank you. So what I'm not yet able to provide you with is the progression-free survival, given that for now, median follow-up is at 8.2 months. What we have at six months is 72.3% of patient that are progression-free at that step. So we haven't yet reached the median PFS. And of course, we don't have yet the overall survival for this patient population. I think these items are very important. As we said, these patients tend to have a poor prognostic. And so, therefore, being able to generate prospective data of combination regimen in this space is very important. So we are eagerly waiting for those longer-term follow-up to define the potential role of this combination in patient with non-clear cell.

Pedro Barata: That's fantastic. Well, Dr. Albiges, I feel like we could stay and talk about this much longer. I really appreciate your taking the time to talk to us. Again, congratulations. Very elegant presentation and I'm looking forward to actually follow-up data and also the publication, right? So again, thank you and congratulations.

Laurence Albiges: Thank you very much.