LITESPARK-022, LITESPARK-011 Trials Reshape the RCC Landscape

In a recent interview following the 2026 ASCO Genitourinary Cancers Symposium, Karie Danielle Keera Runcie, MD, assistant professor of medicine at Columbia University Medical Center, in New York, New York, shared her perspective on two pivotal trials reshaping the treatment landscape for kidney cancer: LITESPARK-022 (NCT05239728) and LITESPARK-011 (NCT04586231).

Dr Runcie first discussed LITESPARK-022, a study investigating the role of adjuvant pembrolizumab (Keytruda) plus belzutifan (Welireg) in patients with intermediate or high risk clear cell kidney cancer. Building on the foundation of the KEYNOTE-564 trial (NCT03142334), which established the benefit of adjuvant pembrolizumab alone, this new combination demonstrated an improvement in disease free survival. While Dr Runcie celebrated this progress as a remarkable step toward curing patients by targeting micro metastatic disease, she also emphasized the critical need for precision. She noted that surgery alone cures a significant number of patients, and adding therapy carries risks of toxicity. To avoid overtreatment, she highlighted the importance of emerging biomarkers, such as KIM-1 and whole genome ctDNA, to better identify who patients truly require aggressive adjuvant therapy.

Turning to the advanced disease setting, Dr Runcie addressed the findings of LITESPARK-011. This trial compared the combination of belzutifan and lenvatinib (Lenvima) against cabozantinib (Cabometyx) in the second-line and refractory setting. The study was significant, she explained, because it showed that the combination improved progression-free survival in this high-risk patient population. Given that many patients do not proceed to a third line of therapy, establishing an effective second-line option is crucial. Perhaps the most surprising outcome, according to Dr Runcie, was that 5% of patients in the combination group achieved a complete response, an uncommon occurrence in the refractory setting. Despite concerns about additive toxicity with combination therapies, she noted that the adverse events were surprisingly manageable, with the known on-target effects of belzutifan being consistent with expectations.