Pedro Barata: Hi, my name is Pedro Barata. I'm a GU medical oncologist at University Hospital Seidman Cancer Center, and it's my pleasure to be joined by Dr. Mauricio Burotto. He's the medical director of Bradford Hill Research Center in Santiago, Chile. And I'm very, very happy to have you here, Mauricio, and I'm hoping we can talk a little bit about this long-term three year follow up of CheckMate-9ER with Cabozantinib/Nivolumab combination. Very important trial. Congratulations for your great presentation during ASCO GU, can you remind, perhaps we'll start there. Can you remind our listeners a little bit of the design of the study with the 9ER?

Mauricio Burotto: Thank you very much for the invitation. Yeah, this trial, big trial, was designed and compares the combination of a nivolumab, the immunotherapy, with Cabozantinib, a TKI, against sunitinib, a long standard treatment for kidney cancer. And the patients were randomized one to one, and the main outcome of the trial was PFS.

Pedro Barata: So we know the study's positive, actually it's practice changing, right?

Mauricio Burotto: Yeah, yeah.

Pedro Barata: Published originally in the New England Journal of Medicine, practice changing because it's shown the cabo-nivo combination to be superior to a TKI that a couple of years ago was actually the standard of care, right?

Mauricio Burotto: Exactly, yes.

Pedro Barata: Can you tell us basically the main findings of the trial There was, and remind me, I think the first results we saw was a follow-up around 16 to 18 months, right?

Mauricio Burotto: Yes.

Pedro Barata: Can you-

Mauricio Burotto: Exactly, yeah.

Pedro Barata: Can you remind me a little bit about the main results at that time?

Mauricio Burotto: Yes, perfect. The main outcomes of the first follow-up was 18.1 months and the main results were the all three efficacy outcomes of PFS, OS, and overall response rates were better with the combination compared with the sunitinib.

Pedro Barata: Right.

Mauricio Burotto: And independent of the AMDC risk factor for kidney cancer patients. That was very practice-changing and then was a follow-up at 32 months. And now is the presentation, was the presentation with a longer follow-up, 44 months. That is the longest follow-up for a combination of TKI and IO combination published in the recent years.

Pedro Barata: Let me talk specifically about your presentation during ASCO GU, right?

Mauricio Burotto: Okay.

Pedro Barata: And it's really, as we said, a longer-term follow-up analysis, a 44 month, right?

Mauricio Burotto: Yes.

Pedro Barata: And so I'm interested to hear from you what exactly were the main findings, what are the take home points, right? With these longer term follow-up analysis cutoff that you would like to highlight?

Mauricio Burotto: Okay, thank you Pedro. I think the main factors are the three main outcomes of PFS, overall survival, and overall response rates, were better with the combination than with monotherapy sunitinib in the ITT population, okay? And if we look the subgroup analysis, we can see that the responses were better with the combination than the monotherapy in all subgroups, but we don't get a statistical significance in the survival or in the PFS for the favorable risk group. And I think that is something that we have to keep in mind. The main benefit of this combination regarding PFS and OS are in the combined intermediate poor risk group. But the responses were better with the combination, much better with the combination than with the monotherapy, regardless of the subgroup by AMDC risk category.

Pedro Barata: I think the findings of that study are really important, as to your point. It's so interesting because we've seen in a number of studies, perhaps the difference between the combination and the TKI are so obvious in the intermediate poor risk and not as obvious for the endpoints that we have in a shorter term with the good risk. And maybe because patients do well for such a longer time in the good risk, it takes it much longer to understand the effect and to appreciate that difference.

Mauricio Burotto: Exactly.

Pedro Barata: Whereas for intermediate and poor risk, unfortunately patients tend to progress and ultimately succumb to the disease sooner. And really the addition of immunotherapy to a TKI in this case, cabo-nivo, is clearly superior early time points compared with sunitinib. Do you think that's a fair summary?

Mauricio Burotto: It's an excellent summary and I will add another point, that we did a post-hoc analysis of the study that in patients who completed two years of nivolumab treatment, this patient has a median time to subsequent therapy of 20 months. And that means that, you know, you have efficacy of the liver treatment after the cessation for almost two years, and that implies a efficacy of nivolumab treatment in this population.

Pedro Barata: There's great news for patients to remain on treatment without progression for a long period of time.

Mauricio Burotto: Exactly. Yeah, that's very important

Pedro Barata: To me, that is really, really important. Because you confirm the superiority of an important IO TKI combination and then over time you continue to see a benefit and appreciate a benefit of patients treating with that combo compared to monotherapy.

Mauricio Burotto: Yeah.

Pedro Barata: So let me ask you a different question. So obviously we're an important investigator for this trial, it was an international trial in Chile. I know you had an important role in that trial, and thank you for that because we really want international representation. Can you speak to us a little bit about the importance of bringing these trials to places like Chile, for instance, right? Other places, US perhaps, where actually including patients from other regions in the globe might impact, the results?

Mauricio Burotto: Yeah.

Pedro Barata: So can you speak to us a little bit about that?

Mauricio Burotto: Yeah, well thank you for that question. I think it's very important to have these trials in countries like Chile, South America or in other regions in the world besides the states and Europe, because it's more representative of the overall population of the world. That's the first thing. And the second thing, in our countries, we have some difficulty in the access to these new treatments. The combination of the AO-IO, the IO-TKI combinations that are very expensive. And people, it's difficult for people to reach and have these treatments. And the clinical trials is a really good option for many, many patients. And that's the reason because we enroll a lot of patients and our goal is to get the best data, the best quality of data, to have the most representatives of our population in the big trials.

Pedro Barata: Right. Well, kudos for that. I mean, this is a huge effort. I know you're playing a big role as a clinical trialist in Chile, in Santiago, Chile. Maybe I'll ask you that, what exactly is happening in Chile, right?

Mauricio Burotto: Yeah.

Pedro Barata: I know you're really well involved, but here's the opportunity for us to maybe give a shout-out to actually what's being done in Chile to increase participation of patients there into clinical studies?

Mauricio Burotto: Yeah, that's a very good point. I think it's important first for doctors and the people involved in building all the infrastructure for doing clinical trials, is to have the time and the commitment to doing this almost 90 or 100% of the time. The problem there is that you are a medical oncologist and you are doing trials as a secondary thing. And I think you have to, in our countries, in order to have a good quality of data, in order to have patients and to enroll and being representative in big trials, you have to commit your time and your efforts first. It has a first place in trials. And that's the difference that we do, we did in our center in Bradford Hill compared to other ones. We professionalize that and we are a committed 100% to clinical trials. We are doing that in the last two years, and I think that make a big difference.

Pedro Barata: Well, it's fantastic to hear that. I mean, as you said, that impact is really tremendous and there's a lot of advantages. Ultimately patients will benefit from that, but I'm so happy to see, we just saw during ASCO GU, we had over 70 countries represented and present here at ASCO GU live, right?

Mauricio Burotto: Yeah.

Pedro Barata: Again, post-Covid, everybody's coming back and it's wonderful to see representation, different countries able to collaborate, investigators to collaborate. We're just chatting about how we could actually come up with different ways to collaborate, right?

Mauricio Burotto: Yeah.

Pedro Barata: And it goes, yes, we have in common is our care and for patients with kidney cancer, and it doesn't really matter where we are in the globe, but actually we're able to actually come together and put those efforts together. So I think, I don't speak for the authors of that particular trial, but as a treating physician, thank you for your efforts to actually enrolling significant amount of patients for CheckMate-9ER. Thank you for presenting longer follow up data because that data is really important for us. It reassures us, I guess, that the combination of cabo-nivo, it's safe and it's vey efficacious for those patients with advanced vascular cell RCC. And thank you for taking the time to be here with us, and I hope to see you soon.

Mauricio Burotto: Thank you very much for the invitation, I'm happy to share with you this information. Thank you very much.