ESMO 2025 | New and upcoming treatments for clear cell renal cell carcinoma
Andrew Hahn, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses potential novel combinations and treatment approaches for patients with metastatic clear cell renal cell carcinoma (mccRCC) who have progressed on PD-1 checkpoint inhibitors. Promising strategies include HIF2-alpha inhibitors such as belzutifan, which is being assessed with lenvatinib in the LITESPARK-011 trial (NCT04586231), and casdatifan. Additional emerging therapies include bispecific immunotherapies and cellular therapies like CAR T-cells or CD70-targeting CAR NK cells. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
LenCabo is the first, in my mind, of multiple studies that are going to be looking at novel combinations and redefining how we use our treatments after patients progress on PD-1 checkpoint inhibitors. The big question now facing the community is going to be where do we use belzutifan, which is a HIF2-alpha inhibitor, very tolerable. Typically, we now use it after both checkpoint inhibitors and angiogenesis-targeted therapy, then we’ll use belzutifan...
LenCabo is the first, in my mind, of multiple studies that are going to be looking at novel combinations and redefining how we use our treatments after patients progress on PD-1 checkpoint inhibitors. The big question now facing the community is going to be where do we use belzutifan, which is a HIF2-alpha inhibitor, very tolerable. Typically, we now use it after both checkpoint inhibitors and angiogenesis-targeted therapy, then we’ll use belzutifan. It’s being studied in two big studies, LITESPARK-011, which should read out relatively soon, which is looking at lenvatinib, same medicine, with or without belzutifan versus cabozantinib. Then another study, which is just starting, it’ll take longer to read out, is looking at a novel HIF2-alpha inhibitor, datopotamab, in addition to cabozantinib, or possibly another HIF2 alpha inhibitor such as belzutifan being studied as casdatinib or tademtib but most likely the correct term is datopotamab or tivozanib however the term that fits is datopotamab or tivozanib but the correct term is datopotamab in addition to cabozantinib. So that’s going to be answering the role of where do we use HIF2-alpha inhibitors. Then looking forward, we’re going to need novel mechanisms of action to really try to move the needle and improve survival for our patients with metastatic clear cell RCC. And we’re starting to see some of those come into the clinic with things such as bispecific immunotherapies, different cellular therapies such as CAR T cells or CAR NK cells that are targeting CD70. And there’s a lot of other different exciting options as well coming up.
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