Series Wrap-up: Novel Therapies for mRCC

Sumanta Kumar Pal, MD: With only a couple of minutes left, we’re going to play a little game to round out the session. I’m going to go around and ask everybody what agent that’s on the horizon for kidney cancer they’re most excited about. Bob, I’ll begin with you. What agent that’s on the horizon, maybe in the pipeline right now, are you most excited about for renal cell carcinoma?

Robert S. Alter, MD: I’m going to go with 2. Toni Choueiri recently presented the HIF trial. It’s going to be good not only as a single agent in second- or third-line therapy but in combination too, as Brad mentioned. And I still think tivozanib is going to be a very active drug. We’ve talked about it. Looking at the TIVO-1 and TIVO-3 studies over the years, we’ve all had a chance to play with it on study. It’s a well-tolerated therapy that is definitely going to have a home. When it comes to market, it’s going to be something we definitely have to take into consideration.

Sumanta Kumar Pal, MD: Excellent. I’m going to ask Brad a question about the HIF2 inhibitor, and then I want to hear his response to the same question. When Toni presented that data at the ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium], it was interesting, because cabozantinib and the HIF2 inhibitor in combination produced a response rate of about 20%, which wasn’t very different from monotherapy with an HIF2 inhibitor. How excited are you about the combination? Am I looking at the data correctly? Is the response rate balanced between the 2 settings?

Bradley A. McGregor, MD: The combination is intriguing. It gives us some great safety data that you can add the HIF2 inhibitor to cabozantinib without increased toxicities. They’re early data. The response rate may not be that different, but what we’ve seen early overall is that HIF2 inhibitors tend to have a long-lasting response and maybe get those responses at 6 months or later. The PFS [progression-free survival] for that combination, while early, was intriguing. Given what we’ve seen with CANTATA, where a lot of patients’ post–I/O [immuno-oncology] median PFS was only 8 months or so, it’s much larger. If that PFS is able to be maintained with longer follow-up, that excites me for this possible synergy between those 2 agents.

Sumanta Kumar Pal, MD: What is your pick for the most exciting compound in the pipeline for renal cell carcinoma?

Bradley A. McGregor, MD: Obviously, we’ve been heavily involved with HIF2 inhibitors. I’m really excited to have a completely novel agent to offer to our patients that seems to be a good partner that we can move into different aspects of the disease. It would be really important.

Sumanta Kumar Pal, MD: Very good. Tom, what about you?

Thomas E. Hutson, DO, PharmD: The HIF2s for maybe fewer adverse effects, maybe equipoise in efficacy, or some other slight efficacy advantage. I’m also excited about having something more combinable. Tivozanib may have that similar property, so I’m looking forward to understanding what the differences are with tivozanib-nivolumab vs an axitinib, I/O–TKI [tyrosine kinase inhibitor] and how it fares. Finally, no one has mentioned this Yervoy issue. Is ipilimumab needed? Is it something that drives the tail of the curve? There’s that triplet trial to see what it really adds. Is that a home run or not?

Sumanta Kumar Pal, MD: Interesting. Yes, absolutely. Dave, what about you then?

David F. McDermott, MD: I agree with what my colleagues have said so far. To add to what they’ve said, the approach that’s going to be most practice changing is adjuvant PD-1. We saw that in melanoma. There’s no reason to doubt that checkpoint blockade won’t be active in at least a subset of patients with kidney cancer. If it is, then it changes the paradigm with a much larger group of patients. It will mean, like in melanoma, we’re going to be treating a subset of patients who are PD-1-exposed when they become metastatic. What do we do for those patients? That brings up the question of what works after PD-1 fails. That’s the biggest question, in not just kidney cancer but all oncology. We’re probably going to be testing some CAR [chimeric antigen receptor] therapies in the next year. Those cellular therapies for kidney cancer make sense to me. We need an answer to that question: What works after checkpoint blockade fails?

Sumanta Kumar Pal, MD: Brilliant. That is a great way to round things out. Tian, how about you?

Tian Zhang, MD: Belzutifan is certainly exciting. Kidney cancer is so immunogenic that I’d love to see some of these novel immunotherapies pan out, like NKTR-214 with a PEGylated IL-2. We’ve used high-dose IL-2 for so long that the PIVOT-09 study is certainly interesting. Then there are also the CAR-Ts. You’re in charge of developing the CD70 CAR T cells, so I’m excited to see cellular therapies come into the kidney cancer space.

Sumanta Kumar Pal, MD: This has been an outstanding discussion, and I really want to thank everybody on this panel for the rich and informed discussion that we’ve had. Thank you all on the panel, and thanks to our viewing audience. We certainly hope that our audience found this OncLive® Peer Exchange® discussion to be useful and informative.

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