What’s Next for RCC Treatment? Promising New Targets and Clinical Trials

In the final segment of this roundtable, the panelists discuss the search for novel targets and strategies to improve renal cell carcinoma (RCC) treatment, particularly in the refractory setting. The conversation highlights promising advancements such as LAG-3, updated interleukins, CAR-T therapies, and bispecific antibodies, as well as the challenges of balancing toxicity and efficacy in these approaches. The panelists also discuss the role of novel therapies in both the frontline and refractory settings, emphasizing the need for innovative, curative strategies. Insights from the TiNivo-2 study are explored, particularly its implications for VEGF inhibitor strategies and its impact on the palliative treatment landscape.

Watch this series from the beginning: TiNivo-2 vs CONTACT-03: Trial Design and Key Differences

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Dr. Beckermann:
And maybe one more question that I think has come up in my mind is, I think, Dr. Hammers and Dr. Pal, you both mentioned one of the things that we’re all hoping, and I think Dr. Choueiri even said at the beginning, is these trials didn’t rescue IO progression. And so what I hear from a lot of people here is “We want to see new targets.”

So I guess twofold question. Are there any exciting targets that you already see on the horizon? And then the second part of that is where do you think new targets should ideally be tested? Do you think we’re doing a disservice to require that these novel targets, whether they’re IO-based or otherwise, be tested in the refractory setting, in late-line setting, show monotherapy activity like this classic in drug design? Or moving them up to see if they actually rather enhance or further optimize frontline checkpoint inhibition.

Dr. Hammers:
Yeah, so I 100 percent agree, obviously. The way I think about it, you have therapies that have curative potential. You have therapies that don’t have curative potential. And I think we need to invest more in combinations in therapies that do have curative potential. And I would say, for most part, that is going to be immunotherapy, at least for kidney cancer.

And I do think there are, I mean, a bunch of new targets. Again, I don’t know which one is going to prevail, but just mechanistically, there are additional immune checkpoints that we need to now figure out is the role for them in kidney cancer. Let’s say LAG3, for example. There’s a triplet study coming in the Kidney Cancer Research Consortium, for example. Updated interleukins that don’t require intensive care unit stays. Would there be something interesting there? Bites. Could there be CAR T-cells, et cetera.

I think there will be huge armamentarium of these things that are coming. One plug, so to say, that I always tell every drug company is, “Please don’t require prior TKI,” right? There’s a bunch of patients who come out of immune checkpoint inhibition who have a tumor burden where they don’t need a TKI, and they can engage directly and with another potential, very interesting, exciting immunotherapy. You don’t have to torture them for a year with a TKI. So I think keep that mind open. I think it will be a very exciting time. And then we go from there.

Dr. Choueiri:
I think his work with Monty leading the field with cellular therapies, we have seen some interesting result. Obviously, toxicity remains a concern, but between CD-70, CA9 and other, we have at least established targets. But I think the progress is going to be slow because of the toxicity.

Dr. Pal:
I was just going to say the exact same thing, Toni. Agree with you. The cell therapy stuff is exciting. Fingers crossed that it pans out in a meaningful way that provides a tox profile that’s at least somewhat comparable to what we’d say with existing agents in the field. So we’ll see how it goes.

But also beyond CAR-T, I know there’s several bites in pipeline that I think are of interest. I like one of the things that Hans said, and I wanted to emphasize that, which is that when I’m in clinic with patients talking to them about second and third-line therapy, one of the things that we acknowledge is that the overarching direction of treatment is palliative. So I don’t have concerns offering trials early in this space that involve novel immunotherapy approaches.

Dr. Beckermann:
That’s great. Thank you all. I think a lot of exciting novel targets and practice-informing trials soon to come in the next one to two years to help us understand in the refractory IO setting how to treat patients. And certainly, TiNivo-2, again, also helpful, showing us in a VEGF or selective TKI that we know to be tolerable, had already proven benefit in the third and fourth-line setting, could move up to that second-line setting, show a PFS that’s very comparable there in the 9.2-month arm, and have a reasonable toxicity profile.

And to everyone’s point here, unfortunately, we recognize right now, our goal post-IO is largely palliative. And so having that efficacy and tolerability is certainly something to consider when we’re thinking about a patient who unfortunately has progressive disease.

So this has been really wonderful to have everyone here this afternoon and talk with each of you, and pick your brains, something I don’t always get the opportunity to do. So truly a pleasure. Thank you all for joining and for chatting, and hope everyone has a wonderful day.