LITESPARK-004
A Phase 2 Study of Belzutifan (PT2977, MK-6482) for the Treatment of Von Hippel Lindau (VHL) Disease-Associated Renal Cell Carcinoma (RCC) (MK-6482-004)
Phase 2N = 61NCT03401788
- Population
- People with VHL disease (germline VHL alteration) and measurable renal cell carcinoma; per the 50-month report, no metastatic disease, no previous systemic anticancer treatment and no tumour larger than 3 cm needing immediate surgery
- Design
- Open-label, single-group phase 2 trial of belzutifan 120 mg orally once daily in patients with renal cell carcinoma associated with von Hippel-Lindau disease. The primary end point was objective response (RECIST 1.1) by an independent central radiology review committee; responses in other VHL-associated neoplasms and safety were also assessed.
- Primary endpoint
- ORR
- Arms
- Belzutifan (experimental, n = 61): Belzutifan 120 mg orally once daily
- People
- Jonasch E, MK-6482-004 Investigators
Show the numbers
| Endpoint | Analysis | Belzutifan | Control | Effect |
|---|---|---|---|---|
| ORRPatients with VHL disease-associated RCC (61 enrolled) | primarymedian follow-up 21.8 monthsJonasch 2021 | 49% (36–62%) | — | Single-group trial: no comparator. Thirty patients had a confirmed partial response (full text, PMC9275515). |
| ORRPancreatic lesions (61 patients) | exploratorymedian follow-up 21.8 monthsJonasch 2021 | 77% | — | 47 of 61 patients. Responses in non-RCC neoplasms were assessed as additional objectives. |
| ORRCentral nervous system haemangioblastomas (50 patients) | exploratorymedian follow-up 21.8 monthsJonasch 2021 | 30% | — | 15 of 50 patients. |
| ORRParticipants with VHL disease-associated RCC who received at least one dose (61 enrolled) | long term-updatemedian follow-up 49.9 monthsSrinivasan 2025 | 67% (54–79%) | — | Seven participants (11%) had a complete response and 34 (56%) a partial response. Thirteen grade 3 treatment-related adverse events occurred in 11 (18%) participants; none had a grade 4 or 5 treatment-related adverse event. |
| Endpoint | Analysis | Belzutifan | Control | Effect |
|---|---|---|---|---|
| ORRPatients with VHL disease-associated RCC (61 enrolled) | primarymedian follow-up 21.8 monthsJonasch 2021 | 49% (36–62%) | — | Single-group trial: no comparator. Thirty patients had a confirmed partial response (full text, PMC9275515). |
| ORRPancreatic lesions (61 patients) | exploratorymedian follow-up 21.8 monthsJonasch 2021 | 77% | — | 47 of 61 patients. Responses in non-RCC neoplasms were assessed as additional objectives. |
| ORRCentral nervous system haemangioblastomas (50 patients) | exploratorymedian follow-up 21.8 monthsJonasch 2021 | 30% | — | 15 of 50 patients. |
| ORRParticipants with VHL disease-associated RCC who received at least one dose (61 enrolled) | long term-updatemedian follow-up 49.9 monthsSrinivasan 2025 | 67% (54–79%) | — | Seven participants (11%) had a complete response and 34 (56%) a partial response. Thirteen grade 3 treatment-related adverse events occurred in 11 (18%) participants; none had a grade 4 or 5 treatment-related adverse event. |
Appears in
Sources
Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, et al. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021;385(22):2036-2046.
Srinivasan R, Iliopoulos O, Beckermann KE, Narayan V, Maughan BL, Oudard S, et al. Belzutifan for von Hippel-Lindau disease-associated renal cell carcinoma and other neoplasms (LITESPARK-004): 50 months follow-up from a single-arm, phase 2 study. Lancet Oncol. 2025;26(5):571-582.