LITESPARK-011
Needs reviewA Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Phase 3N = 747NCT04586231
- Population
- Adults with advanced clear-cell renal cell carcinoma that progressed after anti-PD-1 or anti-PD-L1 therapy
- Design
- Open-label, randomised (1:1), active-controlled phase 3 trial in adults with advanced clear-cell renal cell carcinoma whose disease progressed after anti-PD-1 or anti-PD-L1 therapy (with or without a previous VEGFR tyrosine kinase inhibitor), stratified by IMDC score, line of previous immunotherapy and region. The dual primary end points were progression-free survival by masked independent central review and overall survival.
- Primary endpoint
- PFS, OS
- Arms
- Belzutifan plus lenvatinib (experimental, n = 371): Belzutifan 120 mg plus lenvatinib 20 mg orally once daily
- Cabozantinib (control, n = 376): Cabozantinib 60 mg orally once daily
- People
- Motzer RJ, LITESPARK-011 Investigators
PFSHR 0.70 (95% CI 0.59–0.84)Δ median PFS+4.1 monthsOSHR 0.85 (95% CI 0.68–1.05)Δ median OS+7.3 monthsPFSHR 0.74 (95% CI 0.61–0.89)Δ median PFS+4 months
Show the numbers
| Endpoint | Analysis | Belzutifan plus lenvatinib | Cabozantinib | Effect |
|---|---|---|---|---|
| PFSAll randomly assigned participants | interimmedian follow-up 29 monthsMotzer 2026 | median 14.8 months (11.2–16.6) | median 10.7 months (9.2–11.1) | HR 0.70 (95% CI 0.59–0.84)P<0.0001 (one-sided)Second interim analysis. |
| OSAll randomly assigned participants | interimmedian follow-up 29 monthsMotzer 2026 | median 34.9 months | median 27.6 months (24.0–31.4) | HR 0.85 (95% CI 0.68–1.05)P=0.061 (one-sided)Not significantly different. The 95% CI of the belzutifan plus lenvatinib median was 27.5 to not reached. |
| PFSPatients randomised in LITESPARK-011 (747) as described on the FDA page | primarySource 2026 | median 14.6 months (11.1–16.6) | median 10.6 months (9.2–11.1) | HR 0.74 (95% CI 0.61–0.89)P=0.00095 (one-sided)The page does not give a data cutoff or name the analysis; its values differ slightly from the paper's second interim analysis (14.8 versus 10.7 months, hazard ratio 0.70). The analysis label is a placeholder because the schema has no 'unspecified' value. |
| OSPatients randomised in LITESPARK-011 (747) as described on the FDA page | finalSource 2026 | median 33.7 months (29.0–46.9) | median 28.6 months (24.1–31.4) | HR 0.85 (95% CI 0.70–1.03)The FDA page calls this the final analysis of overall survival and states that it was not statistically significant; the data cutoff is not given. |
| ORRPatients randomised in LITESPARK-011 (747) as described on the FDA page | primarySource 2026 | 53% (47–58%) | 40% (35–45%) | P=0.0002 (one-sided)The page does not name the analysis or give a data cutoff. The analysis label is a placeholder because the schema has no 'unspecified' value. |
| Endpoint | Analysis | Belzutifan plus lenvatinib | Cabozantinib | Effect |
|---|---|---|---|---|
| PFSAll randomly assigned participants | interimmedian follow-up 29 monthsMotzer 2026 | median 14.8 months (11.2–16.6) | median 10.7 months (9.2–11.1) | HR 0.70 (95% CI 0.59–0.84)P<0.0001 (one-sided)Second interim analysis. |
| OSAll randomly assigned participants | interimmedian follow-up 29 monthsMotzer 2026 | median 34.9 months | median 27.6 months (24.0–31.4) | HR 0.85 (95% CI 0.68–1.05)P=0.061 (one-sided)Not significantly different. The 95% CI of the belzutifan plus lenvatinib median was 27.5 to not reached. |
| PFSPatients randomised in LITESPARK-011 (747) as described on the FDA page | primarySource 2026 | median 14.6 months (11.1–16.6) | median 10.6 months (9.2–11.1) | HR 0.74 (95% CI 0.61–0.89)P=0.00095 (one-sided)The page does not give a data cutoff or name the analysis; its values differ slightly from the paper's second interim analysis (14.8 versus 10.7 months, hazard ratio 0.70). The analysis label is a placeholder because the schema has no 'unspecified' value. |
| OSPatients randomised in LITESPARK-011 (747) as described on the FDA page | finalSource 2026 | median 33.7 months (29.0–46.9) | median 28.6 months (24.1–31.4) | HR 0.85 (95% CI 0.70–1.03)The FDA page calls this the final analysis of overall survival and states that it was not statistically significant; the data cutoff is not given. |
| ORRPatients randomised in LITESPARK-011 (747) as described on the FDA page | primarySource 2026 | 53% (47–58%) | 40% (35–45%) | P=0.0002 (one-sided)The page does not name the analysis or give a data cutoff. The analysis label is a placeholder because the schema has no 'unspecified' value. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.7 | 0.59–0.84 |
| OS | 0.85 | 0.68–1.05 |
| PFS | 0.74 | 0.61–0.89 |
| OS | 0.85 | 0.7–1.03 |
- Belzutifan plus lenvatinib (experimental)
- Cabozantinib (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Belzutifan plus lenvatinib | Cabozantinib |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 9 | 65.6% | 55.8% |
| 19 | 41.1% | 29.2% |
| 28 | 26.9% | 16.3% |
| 37 | 17.7% | 9.1% |
- Belzutifan plus lenvatinib (experimental)
- Cabozantinib (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Belzutifan plus lenvatinib | Cabozantinib |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 22 | 64.6% | 57.6% |
| 44 | 41.7% | 33.1% |
| 65 | 27.5% | 19.5% |
| 87 | 17.8% | 11.2% |
Appears in
Sources
Motzer RJ, McDermott R, Park SH, Burotto M, Iacovelli R, Verzoni E, et al. Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial. Lancet. 2026;408(10557):808-820.
FDA. FDA approves belzutifan in combination with lenvatinib for advanced renal cell carcinoma with a clear cell component. Notice, 24 September 2026.