Other Emerging Combination Approaches in RCC

Transcript:

Daniel George, MD: I want to talk about another couple strategies that are emerging. These are early. We’re not really ready to roll these out as successful yet, but they look very promising. One of them, Neeraj, is the axitinib/pembrolizumab combination that Mike Atkins presented.

Neeraj Agarwal, MD: I think this combination—based on the preliminary data that were presented in this meeting with a progression-free survival in treatment-naive patients of 21 months and objective responses of 73%—is really raising the bar beyond what we have seen with the CheckMate-214 trial and the IMmotion151 trial. If these data are really replicable once we see the final results and these numbers are maintained, I think it will be really exciting to see.

Nicholas J. Vogelzang, MD, FASCO, FACP: I think the JAVELIN trial is done, right? That’s sunitinib versus axitinib and avelumab, right?

Neeraj Agarwal, MD: Yes.

Nicholas J. Vogelzang, MD, FASCO, FACP: I don’t know when that closed. It wasn’t that long ago. Brad, you remember that?

Bradley McGregor, MD: That’s right, the JAVELIN trial has been closed in the past couple months. It’s going to be a while. I think to your point from earlier about toxicity synergy, there were other impressive data from axitinib/pembrolizumab, that it was well tolerated. There were grade 3 toxicities of 22% diarrhea and some fatigue, 10%, but we didn’t see this exponential increase in toxicities. I think it has good response and also good tolerability. I think that combination is definitely going to be interesting going forward.

Daniel George, MD: The last combination, Bob, is the one with lenvatinib and everolimus in the front-line setting, but also lenvatinib and pembrolizumab versus sunitinib. Tell us a little bit about that study.

Robert Alter, MD: This is all on the heels of the phase II clinical trial, where the lenvatinib/everolimus data were impressive: so much so that they were seeing numbers of progression-free survival and duration of response similar to, actually better than, what they were seeing with sunitinib in its pivotal phase III clinical trial.

With that enthusiasm, it’s a 3-arm study. It’s called the CLEAR clinical trial using sunitinib as the control arm, still at the 50 mg/day for 4 weeks on and 2 weeks off; using lenvatinib and everolimus, lenvatinib at 18 mg/daily and everolimus at 5 mg/daily, half of the typical dose; and using the lenvatinib and pembrolizumab, recognizing that the combination of immunotherapy and TKI therapy is probably the way of the future. There is, right now, a breakthrough designation using the combination of pembrolizumab and lenvatinib. This is going to be a case of, are the phase II data real? Are we not just looking past sunitinib anymore? Are we now looking at, is it going to be in combination of 2 different agents, a TKI/mTOR or a TKI/I-O? Again, it’s answering a few questions in 1 study.

Transcript Edited for Clarity