The LITESPARK-011 study demonstrated that belzutifan plus lenvatinib significantly improved progression-free survival and objective response rate compared to cabozantinib in patients with advanced clear-cell renal cell carcinoma previously treated with immunotherapy. While overall survival favored belzutifan plus lenvatinib, the difference was not statistically significant at the time of this analysis. The safety profile of belzutifan and lenvatinib was consistent with the known profiles of the individual drugs, with hypertension and anaemia being common adverse events.
Study
|
Randomized, open-label, active-controlled, phase 3 study [LITESPARK-011, NCT04586231] |
| Advanced clear-cell RCC with progression following anti-PD-1 or anti-PD-L1 therapy |
| Belzutifan 120 mg + Lenvatinib 20 mg (n=371) vs Cabozantinib 60 mg (n=376)
|
Efficacy
|
ORR: 53% vs 40% (belzutifan + lenvatinib vs. cabozantinib) (one-sided p=0.0002) |
| mPFS: 14.8 mos vs 10.7 mos (HR 0.70 [0.59-0.84]) |
| mOS: 34.9 mos vs 27.6 mos (HR 0.85 [0.68-1.05])
|
Safety
|
Grade 3-5 AEs: Hypertension (31% vs 29%), Anaemia (19% vs 7%), Diarrhea (8% vs 11%), Fatigue (9% vs 4%), Proteinuria (9% vs 3%), Asthenia (8% vs 5%), Hypoxia (12% vs Not reported) |
| Serious AE: 52% vs 44% |
| Treatment discontinuation due to AE: 19% vs 5% |
| Treatment-related deaths: 1% vs <1%
|
Lancet. Published online August 12, 2026
http://doi.org/10.1016/S0140-6736(26)01089-5
Reviewed by Ulas D. Bayraktar, MD on Aug 20, 2026
