A recent open-label phase 2 study led by Toni Choueiri, MD (from Dana-Farber Cancer Institute), has reported promising interim results for combination therapy of cabozantinib and belzutifan in patients with advanced renal cell carcinoma (kidney cancer) who have previously undergone immunotherapy and up to two systemic treatment regimens.
The research, published in The Lancet Oncology, suggests that the combination of these two drugs may fill an unmet need for patients who experience disease progression despite immunotherapy.
Immunotherapies, such as anti-PD-1 and anti-PD-L1, have become standard first-line therapies for patients with advanced renal cell carcinoma. But most patients eventually experience disease progression, and there is no consensus on the appropriate therapy to use next. In this study, researchers investigated the combination of cabozantinib, a VEGF tyrosine kinase inhibitor (TKI), and belzutifan, a HIF-2α inhibitor, for the first time. Belzutifan has previously shown antitumor activity and favourable safety in heavily pretreated advanced kidney cancer.
The researchers had previously reported results for cohort 1 of the LITESPARK-003 trial. The present study reports on cohort 2, which includes patients diagnosed with advanced clear cell renal cell carcinoma who have previously received immunotherapy and up to two systemic treatment regimens. After a median follow-up of 24 months, the interim results show promising antitumor activity in this pre-treated patient group, with a disease control rate of 92% and a manageable safety profile.
While immunotherapy has significantly changed the treatment landscape for advanced renal cell carcinoma, questions remain about what therapy to provide when patients experience disease progression on immunotherapy. The combination of cabozantinib and belzutifan in this study demonstrates promising antitumor activity in a pre-treated patient group, suggesting that this combination might fill an unmet need for patients who have not responded to immunotherapy.
According to the researchers, the results provide a rationale for further study of combining a VEGF TKI and a HIF-2α inhibitor in the treatment of advanced kidney cancer. This combination therapy could potentially offer patients a new treatment option that is more effective than currently available therapies.
The study was funded by Merck Sharp & Dohme (a subsidiary of Merck & Co) and the National Cancer Institute. As researchers continue to explore combination therapies for advanced renal cell carcinoma, it is crucial to maintain a focus on optimizing patient outcomes and minimizing side effects. The positive interim results from this phase 2 study offer a promising start in addressing the unmet needs of patients who have experienced disease progression on immunotherapy.
The combination of cabozantinib, a VEGF TKI, and belzutifan, a HIF-2α inhibitor, shows promising antitumor activity in patients with advanced renal cell carcinoma who have previously undergone immunotherapy and up to two systemic treatment regimens. These interim results provide a rationale for further study of this combination therapy, which has the potential to fill an unmet need and improve outcomes for patients experiencing disease progression on immunotherapy.