Advancing RCC Treatment: Trials to Watch and Promising Novel Approaches

In the final part of this roundtable series, Michael Atkins, MD; Laurence Albiges, MD, PhD; Chandler Park, MD; Mike Lattanzi, MD; and Alan Tan, MD, share their thoughts on the most anticipated upcoming kidney cancer trials. They highlight key studies such as the CARE-1 and Lightspark-12 trials, exploring new combinations like IO-IO regimens and the potential role of novel therapies like HIF-2 alpha inhibitors. The panel also discusses the ongoing evolution of treatment paradigms, from triplet therapies to microbiome research, with a focus on raising the standard of care for patients with kidney cancer.

Watch this series from the beginning: Balancing Risks and Rewards in RCC: IO Combinations for Different Patient Profiles

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Dr. Atkins:
Okay. We’re moving on to the last section. Laurence, I’m going to ask you this question because I know you have strong opinions about this, but what trial data are you most waiting for? 

Dr. Albiges:
So, well, there are many things that we’re waiting for. I personally am very involved in the frontline IOI versus IO/TKI as you understood. So the CARE-1 trial is going to take a while to enroll, but this is something that I really feel could make a difference given that the triplet is not yet a standard and we need to really change the game so that it becomes a standard and we’re not there yet. I believe that we’ve made progress for the non-clear cell frontline strategy. And I’m happy that we now have adjuvant in RCC, that is really something that is fantastic that we have early intervention. And I hope that in the future we can better select those patients for adjuvant strategy, and this is where we’re back with KIM-1. 

Dr. Atkins:
Good avoidance of the answer. How about you Alan? What trials are you looking forward to? 

Dr. Tan:
Well, I already mentioned PDIGREE, but we’re not going to get a readout for a while because the primary endpoint is landmark three-year overall survival. But emerging is a Lightspark-12, that’s another triplet. We already saw from a Cosmic-313 that the Nivo-Cabo-Ipi was probably too toxic. So we’re not going to do triplet in that setting. But Merck has also done a triplet looking at HIF-2 alpha combination. So we don’t know if a triplet with HIF-2 alpha is better tolerated and has more efficacy as well. But I think what the future should be moving towards is we need to build upon the IO/IO backbone. I don’t think we should be doing more in combination with TKI. I think we’ve hit a plateau there, but we need to raise the tail of the curve from CheckMate 214, whether that’s adding LAG-3 or some other IO T-cell engagers, etc. 

Dr. Atkins:
How about you, Mike? 

Dr. Lattanzi:
Yeah, I certainly agree with everything that y’all said. I think in RCC, right now there are a lot of combination studies going on, both in the front line and in the treatment refractory setting. Frankly, I think that’s unlikely probably to increase the cure rate. And what we really need are novel mechanisms. So frankly, I’m most excited about the early drug development around novel immunotherapies, novel immune bispecifics and radioligand therapy. 

Dr. Atkins:
Chandler? 

Dr. Park:
Yeah, I think one of the things that really intrigues me here is the turning the cold tumors hot. I think that Monty Powell had some really good data on gut microbiome. And even at ESMO this year, this question of fecal transplant, and not necessarily with the colonoscopy, but they actually had an arm that did a pill, and so that makes it much more convenient. So I’m very intrigued by this. The data from the Brazilian group was very promising, and I can see something like this maybe progress and maybe more mature and see what the data looks like. 

Dr. Atkins:
I think this has been a great discussion. I think we’ve completed, finished our time. And I really thank you all for your insights and hopefully everybody appreciated the debate.