LITESPARK-005
Needs reviewA Study of Belzutifan (MK-6482) Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005)
Phase 3N = 746NCT04195750
- Population
- Adults with advanced clear-cell renal cell carcinoma previously treated with an immune checkpoint inhibitor and antiangiogenic therapy
- Design
- Multicentre, open-label, active-controlled phase 3 trial: participants with advanced clear-cell renal cell carcinoma who had previously received immune checkpoint and antiangiogenic therapy were randomised 1:1 to belzutifan or everolimus until progression or unacceptable toxic effects. The dual primary end points were progression-free survival and overall survival; the key secondary end point was confirmed objective response. The paper reports 746 randomised participants; the registry total of 755 also counts 9 non-randomised safety run-in participants.
- Primary endpoint
- PFS, OS
- Arms
- Belzutifan (experimental, n = 374): Belzutifan 120 mg orally once daily
- Everolimus (control, n = 372): Everolimus 10 mg orally once daily
- People
- Choueiri TK, LITESPARK-005 Investigators
Δ median PFS0 monthsΔ 18-month PFS+15.7 pointsΔ ORR+18.4 pointsOSHR 0.88 (95% CI 0.73–1.07)Δ median OS+3.3 monthsΔ 18-month OS+4.6 points
Show the numbers
| Endpoint | Analysis | Belzutifan | Everolimus | Effect |
|---|---|---|---|---|
| PFSRandomised participants as described in the abstract (analysis population not stated there) | interimmedian follow-up 18.4 monthsChoueiri 2024 | median 5.6 months; 24% at 18 mo | median 5.6 months; 8.3% at 18 mo | P=0.002 (two-sided)First interim analysis; the abstract does not report a hazard ratio. The medians were identical, so the difference is in the 18-month progression-free rates. P met the prespecified significance criterion. |
| ORRRandomised participants as described in the abstract (analysis population not stated there) | interimmedian follow-up 18.4 monthsChoueiri 2024 | 21.9% (17.8–26.5%) | 3.5% (1.9–5.9%) | P<0.001Key secondary end point at the first interim analysis; met the prespecified significance criterion. |
| OSRandomised participants as described in the abstract (analysis population not stated there) | interimmedian follow-up 25.7 monthsChoueiri 2024 | median 21.4 months; 55.2% at 18 mo | median 18.1 months; 50.6% at 18 mo | HR 0.88 (95% CI 0.73–1.07)P=0.20 (two-sided)Second interim analysis; did not meet the prespecified significance criterion. |
| PFSRandomised patients (746) as described on the FDA page | interimSource 2023 | median 5.6 months (3.9–7.0) | median 5.6 months (4.8–5.8) | HR 0.75 (95% CI 0.63–0.90)P=0.0008 (one-sided)FDA announcement page (14 December 2023): hazard ratio from the blinded independent central review analysis; the page states that the Kaplan-Meier curves reflected non-proportional hazards and gives no data cutoff or analysis name (the analysis label here is a placeholder because the schema has no 'unspecified' value). The medians agree with the paper's first interim analysis. The page states that overall survival was immature, with 59% of deaths reported. |
| Endpoint | Analysis | Belzutifan | Everolimus | Effect |
|---|---|---|---|---|
| PFSRandomised participants as described in the abstract (analysis population not stated there) | interimmedian follow-up 18.4 monthsChoueiri 2024 | median 5.6 months; 24% at 18 mo | median 5.6 months; 8.3% at 18 mo | P=0.002 (two-sided)First interim analysis; the abstract does not report a hazard ratio. The medians were identical, so the difference is in the 18-month progression-free rates. P met the prespecified significance criterion. |
| ORRRandomised participants as described in the abstract (analysis population not stated there) | interimmedian follow-up 18.4 monthsChoueiri 2024 | 21.9% (17.8–26.5%) | 3.5% (1.9–5.9%) | P<0.001Key secondary end point at the first interim analysis; met the prespecified significance criterion. |
| OSRandomised participants as described in the abstract (analysis population not stated there) | interimmedian follow-up 25.7 monthsChoueiri 2024 | median 21.4 months; 55.2% at 18 mo | median 18.1 months; 50.6% at 18 mo | HR 0.88 (95% CI 0.73–1.07)P=0.20 (two-sided)Second interim analysis; did not meet the prespecified significance criterion. |
| PFSRandomised patients (746) as described on the FDA page | interimSource 2023 | median 5.6 months (3.9–7.0) | median 5.6 months (4.8–5.8) | HR 0.75 (95% CI 0.63–0.90)P=0.0008 (one-sided)FDA announcement page (14 December 2023): hazard ratio from the blinded independent central review analysis; the page states that the Kaplan-Meier curves reflected non-proportional hazards and gives no data cutoff or analysis name (the analysis label here is a placeholder because the schema has no 'unspecified' value). The medians agree with the paper's first interim analysis. The page states that overall survival was immature, with 59% of deaths reported. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.88 | 0.73–1.07 |
| PFS | 0.75 | 0.63–0.9 |
- Belzutifan (experimental)
- Everolimus (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Belzutifan | Everolimus |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 4 | 61.0% | 61.0% |
| 7 | 42.0% | 42.0% |
| 11 | 25.6% | 25.6% |
| 14 | 17.7% | 17.7% |
- Belzutifan (experimental)
- Everolimus (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Belzutifan | Everolimus |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 13 | 65.6% | 60.8% |
| 27 | 41.7% | 35.6% |
| 40 | 27.4% | 21.6% |
| 54 | 17.4% | 12.6% |