CaboPoint Study: Cabozantinib After Checkpoint Inhibitor Therapy in Patients with Advanced Renal Cell Carcinoma - Laurence Albiges

March 20, 2023

Laurence Albiges joins Pedro Barata to discuss the CaboPoint study, a clinical trial designed to examine the question of activity and safety of cabozantinib single agent in patients who failed first-line combination therapy for advanced renal cell carcinoma (aRCC). The study has two subgroups - Cohort A and Cohort B. Cohort A is the activity of cabozantinib after nivolumab/pembrolizumab, and Cohort B is the activity of cabozantinib after VGF/TKI plus IO. The primary endpoint of the study is the response rate. Albiges highlights the data reported showing a 30% response rate across the two subgroups, with a split of 32% in patients in cohort A, and a bit more than 25% in cohort B which was presented at the 2023 GU ASCO meeting.


Laurence Albiges, MD, PhD, Medical Oncologist, Gustave Roussy Cancer Campus, University of Paris Sud, France

Pedro C. Barata, MD, MSc, Leader of the Clinical GU Medical Oncology Research Program, University Hospitals Seidman Cancer Center, Associate Professor of Medicine, Case Western University, Cleveland, OH

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Pedro Barata: I'm joined today by Dr. Laurence Albiges. She's obviously a big key opinion leader in the kidney cancer world. I'm very, very happy to first congratulate you for the great job presenting CaboPoint, an important study in my opinion, and an unmet need. You are the leader of the medical oncology group at Gustave Roussy in France, so thank you for joining us today.

Laurence Albiges: Thank you, Pedro. It's a pleasure to be here today. Thank you.

Pedro Barata: Absolutely. And I would like to chat with you a little bit about, first, the interim results for your trial, it's a relevant trial, and we're starting having results on that, and then where the field is moving from that perspective, especially in the refractory setting. But I guess first things first. So some of the audience might not be as familiar with the trial. Can you remind us what the concept was? I know you break it down in cohorts. Can you tell us a little bit about the trial schema?

Laurence Albiges: Sure. So all our guidelines state combination therapy as first-line for clear cell RCC. It's either IO/IO, namely, nivolumab plus ipilimumab, or IO/TKI. But the question is, what shall we do afterwards? And there is a need to know what's the activity and safety of the current agents available that we routinely use in second-line. CaboPoint Study has been designed to cover the question of activity and safety of cabozantinib single agent in patient who failed first-line combination therapy. We need to answer that question, and so CaboPoint was designed to look at the activity of cabozantinib, either after nivolumab/pembrolizumab, that's cohort A, or after VGF/TKI plus IO, that's cohort B.

Pedro Barata: That's wonderful. And I really think it's important, because to your point, we all use TKIs in the refractory space, but a lot of the data we use to make those decisions derives from either pre IO based approaches in the front-line space, or some of the retrospective experiences the different groups have. And so, I really think it's relevant to getting prospective data in the actual and current management of patients with advances RCC. So kudos for that. Now, so with that said, can you kind of tell us what are kind of the take home points or the preliminary highlights from your data you just presented?

Laurence Albiges: So this interim analysis of CaboPoint study was the pre-planned analysis when we had about 80% of patient in cohort A, nivolumab plus ipilimumab refractory patient, for which we had more than three months of follow up. The primary endpoint of the study is response rate. And what we are reporting is actually a very nice response rate of 30% across the two subgroup, with a split of 32% in patient in cohort A, and a bit more than 25% in cohort B. So clearly, great activity of cabozantinib single agent after failure of combination therapy.

Pedro Barata: Right. That's wonderful, because when we think of the different TKIs available in the refractory setting, we probably would argue that cabo is one of the top leaders, right? It's a preferred regimen for a lot of us. So it's good to know that the activity seems to be there. So you have this primary endpoint response rate, but I know you're looking for other endpoints beyond response rate. And the question I also want to ask you is, we tend to think that if you don't expose a patient to a TKI upfront, maybe we'll see more activity in the refractory setting, because it's the first time patient is seeing a TKI, and that has been used as an argument, I guess, or rationale for folks to go with IO/IO approach, instead of an IO/TKI, for instance. From what you've seen thus far from your trial, can we make those claims? What are your thoughts about that?

Laurence Albiges: So in this interim analysis we could analyze 68 patient, sorry, 88, patient 60 after nivolumab plus ipilimumab, and 28 after IO/TKI, which was most predominantly axitinib plus pembrolizumab. You are right. The response rate was higher in patient who had never seen TKI. But to me, we had a very decent, over 25%, response rate in patient who did fail prior TKI, such as axitinib in combination with pembrolizumab. So here, yes, there is a role for subsequent VGF targeting here with cabozantinib.

Pedro Barata: Right.

Laurence Albiges: When we look at the subgroup analysis, we see activity across the different subgroup. What was very interesting to me is that, in patient who were refractory to first-line, meaning, had less than six months of treatment duration in first-line, actually derive great benefit of cabozantinib, with more than 32% of response rate, so clear activity. And this stressed the fact that in a patient who failed first-line, including Hippel progressing, it is important that the patient get access to second-line, put in VGF/TKI.

Pedro Barata: Well, this a very powerful message, right? Because unfortunately we do know, we do encounter kind of those primary progressors to IO based combos. And even if that doesn't happen around three months, can happen soon after. And so it sounds like those are good news for patients, because we have a therapy that prospectively confirms to have activity for patients who unfortunately won't respond to an IO based approach.

I guess, maybe one last question before I let you go. What do you envision being the next steps for this particular trial moving forward? I know you have planned out other analysis and the study will read out, but can you share with us a little bit what to expect from that trial?

Laurence Albiges: Sure. So we'll have full analysis on all the patients enrolled later this year. So we are waiting for this, and we'll address other endpoints, such as PFS and so on. But to your point, I think the question that is open now is, is single agent TKI, here cabozantinib, enough, or should we go for a combination with an IO regimen on top of TKI? And so, we're all waiting for the CONTACT-03 study, which will be the question of sustained PD-1, PD-L1 inhibition after initial treatment with IO and TKI. So hopefully CONTACT-03 will let us know if we should have an addition of PD-L1 inhibition in those patients.

Pedro Barata: Yeah. I know that's a great message. As a way to wrap this up, CONTACT-03 is really important, right? Exploring cabo with atezolizumab in this setting, a salvage setting. And I completely agree with you, as we see the emergence of the IO based combos, I guess, we set it up in the front-line clear cell, we're exploring the non-clear cell, and we also exploring the salvage setting. So to your point, it's almost like it's a beautiful segway from your trial, right? We see that cabo is active in the salvage setting, and maybe your data is probably one of the best leveraging that. And then the next question will hopefully be answered, right? Whether or not we should be start thinking about, again, an IO based approach, perhaps with cabo, upon progression.

Well, wonderful discussion. Thank you so much for taking your time. Congratulations for your fantastic presentation as usual. And we'll probably going to be here to talk again with more mature follow up on your trial. Good job. Thank you.

Laurence Albiges: Thank you very much.