Dr Hammers on Ongoing Investigations in Advanced RCC

Hans Hammers, MD, PhD, professor, Department of Internal Medicine, member, Division of Hematology and Oncology, inaugural Eugene P. Frenkel, MD Scholar in Clinical Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses ongoing and planned investigations with the use of HIF2α inhibitors and triplet therapies in patients with advanced renal cell carcinoma (RCC).

Looking to the future of RCC treatment, there are a few areas of interest, Hammers begins. Firstly, additional data regarding the use of HIF2α inhibitors in this treatment arena are anticipated, as these agents are positioned to change the landscape, Hammers says. Notably, this is a new class of drug and is uniquely well tolerated. In patients with conducive biology, HIF2α inhibitors can lead to prolonged responses and unique quality of life outcomes, Hammers explains.

For example, the HIF2α inhibitor belzutifan (Welireg) was FDA approved in August 2021 for patients with von Hippel-Lindau disease who require therapy for associated RCC. This agent continues to derive significant and clinically meaningful benefit in the ongoing phase 3 LITESPARK-005 trial (NCT04195750) for patients with advanced RCC. Although HIF2α inhibitors continue to be investigated as single agents, these inhibitors are also being examined in combination with TKIs, as well as in triplet therapies currently under study in clinical trials, Hammers expands.

One such triplet therapy, lenvatinib (Lenvima) with belzutifan and pembrolizumab (Keytruda), is under investigation in patients with solid tumors in an ongoing phase 3 study (NCT04736706), he continues. This trial has just accrued, so the data will read out in years to come, he explains.

Another triplet therapy for patients with RCC includes the combination of cabozantinib (Cabometyx) with nivolumab (Opdivo) and ipilimumab (Yervoy), which is under investigation in the phase 3 COSMIC-313 trial (NCT03937219). However, this combination has led to excessive toxicity, Hammers emphasizes. If this triplet is approved, Hammers does not believe it will be widely used because of its associated liver toxicities. However, research is ongoing to find agents that can be combined with reasonable toxicities and good long-term outcomes, Hammers concludes.