LITESPARK-005
The HIF-2α inhibitor beat the old standard everolimus after immunotherapy and targeted therapy had failed, with durable responses in a subset.
PFS HR 0.75; ORR 22.7% vs 3.5%; OS HR 0.88 (not significant). FDA approval December 2023. Anaemia and hypoxia are on-mechanism toxicities.
Setting
Advanced clear-cell RCC after PD-1/PD-L1 and VEGF-TKI: belzutifan vs everolimus
Phase
Phase 3
Sponsor
Merck
Registry
Headline result
PFS HR 0.75; ORR 22.7% vs 3.5%; OS not significant.
Reported
2023
Enrolled
746
Replication
Belzutifan activity replicated in VHL disease (LITESPARK-004); first-line combination (LITESPARK-012) did not meet its goal in 2026.
In plain words
What these results mean for people, not percentages
Progression-free survivalprimarysurrogate endpoint
- The treated group had about 25 percent lower chance of the event at any given time (hazard ratio 0.75).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Objective response rateresponse endpoint
- 22.7 vs 3.5 out of 100 had their tumour shrink with Belzutifan compared with Everolimus; 19.2 more per 100.
- Roughly one extra person helped for every 5 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
Be careful
- These results apply to the people the trial enrolled: Advanced clear-cell RCC after PD-1/PD-L1 and VEGF-TKI: belzutifan vs everolimus. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (PD-1); the result should not be assumed for people whose cancer does not have it.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
746 participants enrolled.
Objective response rate
Belzutifan22.7 of 100
Everolimus3.5 of 100
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Belzutifan | 374 | — | 0.75 (0.63–0.9) | — | link |
| Everolimus | 372 | — | ||||
| Objective response rate | Belzutifan | — | 22.7% | — | — | — |
| Everolimus | — | 3.5% |
Replication
Belzutifan activity replicated in VHL disease (LITESPARK-004); first-line combination (LITESPARK-012) did not meet its goal in 2026.