Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial

Summary

The BELIEVE-VHL Trial is a prospective real-life study designed to evaluate the therapeutic effects, benefits, and adverse effects of belzutifan, as well as the timing of treatment response and disease progression in patients with von Hippel-Lindau (VHL) syndrome.

Timeline

Start

2024-01-01

Primary completion

2026-02-01

Completion

2030-01-01

Publications

• Background Else T, Jonasch E, Iliopoulos O, Beckermann KE, Narayan V, Maughan BL, Oudard S, Maranchie JK, Iversen AB, Goldberg CM, Fu W, Perini RF, Liu Y, Linehan WM, Srinivasan R. Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study. Clin Cancer Res. 2024 May 1;30(9):1750-1757. doi: 10.1158/1078-0432.CCR-23-2592.
• Background Eriksson M, Lindstrom B. Validity of Antonovsky's sense of coherence scale: a systematic review. J Epidemiol Community Health. 2005 Jun;59(6):460-6. doi: 10.1136/jech.2003.018085.
• Background Bagattini AM, Camey SA, Miguel SR, Andrade MV, de Souza Noronha KVM, de C Teixeira MA, Lima AF, Santos M, Polanczyk CA, Cruz LN. Electronic Version of the EQ-5D Quality-of-Life Questionnaire: Adaptation to a Brazilian Population Sample. Value Health Reg Issues. 2018 Dec;17:88-93. doi: 10.1016/j.vhri.2017.11.002. Epub 2018 May 11.
• Background Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425.
• Background Choueiri TK, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Michaelson MD, Appleman LJ, Thamake S, Perini RF, Zojwalla NJ, Jonasch E. Inhibition of hypoxia-inducible factor-2alpha in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021 May;27(5):802-805. doi: 10.1038/s41591-021-01324-7. Epub 2021 Apr 22.
• Background Varshney N, Kebede AA, Owusu-Dapaah H, Lather J, Kaushik M, Bhullar JS. A Review of Von Hippel-Lindau Syndrome. J Kidney Cancer VHL. 2017 Aug 2;4(3):20-29. doi: 10.15586/jkcvhl.2017.88. eCollection 2017.
• Background Priesemann M, Davies KM, Perry LA, Drake WM, Chew SL, Monson JP, Savage MO, Johnston LB. Benefits of screening in von Hippel-Lindau disease--comparison of morbidity associated with initial tumours in affected parents and children. Horm Res. 2006;66(1):1-5. doi: 10.1159/000093008. Epub 2006 Apr 27.
• Background Daniels AB, Tirosh A, Huntoon K, Mehta GU, Spiess PE, Friedman DL, Waguespack SG, Kilkelly JE, Rednam S, Pruthi S, Jonasch EA, Baum L, Chahoud J; International VHL Surveillance Guidelines Consortium. Guidelines for surveillance of patients with von Hippel-Lindau disease: Consensus statement of the International VHL Surveillance Guidelines Consortium and VHL Alliance. Cancer. 2023 Oct 1;129(19):2927-2940. doi: 10.1002/cncr.34896. Epub 2023 Jun 19. No abstract available.
• Background Krauss T, Ferrara AM, Links TP, Wellner U, Bancos I, Kvachenyuk A, Villar Gomez de Las Heras K, Yukina MY, Petrov R, Bullivant G, von Duecker L, Jadhav S, Ploeckinger U, Welin S, Schalin-Jantti C, Gimm O, Pfeifer M, Ngeow J, Hasse-Lazar K, Sanso G, Qi X, Ugurlu MU, Diaz RE, Wohllk N, Peczkowska M, Aberle J, Lourenco DM Jr, Pereira MAA, Fragoso MCBV, Hoff AO, Almeida MQ, Violante AHD, Quidute ARP, Zhang Z, Recasens M, Diaz LR, Kunavisarut T, Wannachalee T, Sirinvaravong S, Jonasch E, Grozinsky-Glasberg S, Fraenkel M, Beltsevich D, Egorov VI, Bausch D, Schott M, Tiling N, Pennelli G, Zschiedrich S, Darr R, Ruf J, Denecke T, Link KH, Zovato S, von Dobschuetz E, Yaremchuk S, Amthauer H, Makay O, Patocs A, Walz MK, Huber TB, Seufert J, Hellman P, Kim RH, Kuchinskaya E, Schiavi F, Malinoc A, Reisch N, Jarzab B, Barontini M, Januszewicz A, Shah N, Young WF Jr, Opocher G, Eng C, Neumann HPH, Bausch B. Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors. Endocr Relat Cancer. 2018 Sep;25(9):783-793. doi: 10.1530/ERC-18-0100. Epub 2018 May 10.
• Background Dallagnol TN, Da Cas E, Junior OR, Casali-da-Rocha JC. Comprehensive characterization and building of National Registry of von Hippel-Lindau disease in Brazil. Mol Genet Genomic Med. 2023 Apr;11(4):e2136. doi: 10.1002/mgg3.2136. Epub 2023 Jan 10.
• Background Gomy I, Molfetta GA, de Andrade Barreto E, Ferreira CA, Zanette DL, Casali-da-Rocha JC, Silva WA Jr. Clinical and molecular characterization of Brazilian families with von Hippel-Lindau disease: a need for delineating genotype-phenotype correlation. Fam Cancer. 2010 Dec;9(4):635-42. doi: 10.1007/s10689-010-9357-2.
• Background Maher ER, Yates JR, Harries R, Benjamin C, Harris R, Moore AT, Ferguson-Smith MA. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990 Nov;77(283):1151-63. doi: 10.1093/qjmed/77.2.1151.
• Background Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol. 2004 Dec 15;22(24):4991-5004. doi: 10.1200/JCO.2004.05.061.
• Background Rocha JC, Silva RL, Mendonca BB, Marui S, Simpson AJ, Camargo AA. High frequency of novel germline mutations in the VHL gene in the heterogeneous population of Brazil. J Med Genet. 2003 Mar;40(3):e31. doi: 10.1136/jmg.40.3.e31. No abstract available.
• Background Choyke PL, Glenn GM, Walther MM, Patronas NJ, Linehan WM, Zbar B. von Hippel-Lindau disease: genetic, clinical, and imaging features. Radiology. 1995 Mar;194(3):629-42. doi: 10.1148/radiology.194.3.7862955.
• Background Chittiboina P, Lonser RR. Von Hippel-Lindau disease. Handb Clin Neurol. 2015;132:139-56. doi: 10.1016/B978-0-444-62702-5.00010-X.

Drugs

Indications