KEY TAKEAWAYS
- The Phase II LITESPARK-004 study (NCT03401788) explored the possibility of using Belzutifan for treating VHL Disease-Associated RCC.
- The study aimed to measure the ORR among patients undergoing Belzutifan treatment and to analyze the reported follow-ups.
- The primary outcome measure was ORR which was 64% at the average follow-up of 37.8 months.
- The results suggest that belzutifan could be a potential treatment option for patients with VHL disease-associated neoplasms such as RCC, pancreatic neuroendocrine tumors (pNET), CNS hemangioblastomas, or retinal hemangioblastomas.
In the Phase II LITESPARK-004 trial, patients with a germline VHL alteration, fewer than one measurable nonmetastatic RCC tumor, were eligible for oral belzutifan 120 mg once daily until disease progression, intolerable toxicity, or withdrawal. However, the RCC tumor should not have been larger than 3 cm, which required immediate surgery. The patients must not have a history of systemic anticancer therapy, with an ECOG PS 0-1 score. The secondary endpoints were TTR, DOR, and safety, while the primary endpoint was ORR.
About 38 of 61 patients (62%) still received treatment at the follow-up. The major causes of treatment discontinuation were patient choice (n = 11; 18%) and disease progression (n = 6; 10%). The average follow-up was 37.8 months (36.1-46.1 mo). The ORR was 64% (95% CI 50.6-75.8; 4 CRs, 35 PRs) of 61 patients with RCC. The median DOR was not attained (5.4+ to 35.8+ mo), and the median TTR was 11.1 mo (range, 2.7-30.5 mo).
ORR was 91% (95% CI 70.8-98.9; 7 CRs, 13 PRs) for the 22 patients with pNET; median DOR (range, 11.0+ to 37.3+ mo) was not attained. The ORR of 50 patients with CNS hemangioblastomas was 44% (95% CI 30.0-58.7; 4 CRs, 18 PRs); the median DOR (3.7+ to 38.7+ mo) was not reached. In 12 patients with retinal hemangioblastomas, all 16 evaluable eyes exhibited improvement.
Anemia was the most prevalent TRAE (n = 7; 11%) in grade 3 and happened in 18% of patients (n = 11). There were no TRAEs for grades 4 or 5. Additional follow-up revealed no new safety discoveries.
Thus, in the 3+ years’ follow-up, Belzutifan continued to exhibit clinically significant antitumor activity, enduring responses, and a manageable safety profile in VHL disease-associated RCC, pNET, CNS, and retinal hemangioblastomas.
Source:https://cslide.ctimeetingtech.com/esmo2022/attendee/confcal/show/session/273
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03401788
Srinivasan, R., Rathmell, W.K., Narayan, V., Maughan B.L., Oudard, S., Else, T., Maranchie, J.K., Perini, R.F., Liu, Y., Jonasch, E. (2022) LBA69 – Belzutifan, a HIF-2α Inhibitor, for von Hippel-Lindau (VHL) disease-associated neoplasms: 36 months of follow-up of the phase II LITESPARK-004 study. ESMO Congress 2022 – Conference Calendar.
