LITESPARK-011 Could Redefine Second-Line Therapy in Metastatic RCC

In an interview, Rahul Parikh, MD, PhD, of University of Kansas KU Medical Center, highlighted anticipation around late-breaking abstract LBA417 at the 2026 ASCO Genitourinary Cancers Symposium. The presentation, to be delivered by Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, will report findings from the phase 3 LITESPARK-011 trial (NCT04586231), which evaluates second-line treatment strategies for metastatic renal cell carcinoma.

Parikh explained that frontline therapy in this disease typically consists of a VEGF tyrosine kinase inhibitor combined with immunotherapy or dual immunotherapy. The rationale for LITESPARK-011 stems from the earlier CONTACT-03 trial (NCT043338269), which evaluated whether rechallenging patients with immunotherapy plus a VEGF TKI improved outcomes compared with a VEGF TKI alone. In CONTACT-03, atezolizumab (Tecentriq) combined with cabozantinib (Cabometyx) produced a median progression-free survival of approximately 10.6 months, compared with 10.8 months for cabozantinib monotherapy, with a hazard ratio for progression or death of 1.03 and similar overall survival. These findings helped establish cabozantinib alone as a commonly used second-line option.

LITESPARK-011 builds on this foundation by testing a novel combination of belzutifan (Welireg), a HIF-2α inhibitor, with the VEGF TKI lenvatinib (Lenvima) versus cabozantinib monotherapy. According to Parikh, the study’s primary end points are time to progression and overall survival. He emphasized that safety comparisons between the 2-drug regimen and single-agent therapy will be critical, given the potential toxicity trade-offs.

Parikh underscored that, if positive, the trial could meaningfully shift the second-line treatment paradigm in metastatic renal cell carcinoma by establishing a new combination standard beyond current monotherapy approaches.