Isa-VRD in TIE HRMM

Summary

This is a multicenter, prospective, randomized controlled trial designed to compare the quadruplet regimen of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRD) with the standard triplet regimen (VRD) in newly diagnosed, transplant-ineligible patients with high-risk multiple myeloma (HRMM). Primary Hypothesis: The addition of isatuximab to VRD will significantly improve the MRD negativity rate at 12 months compared to VRD alone in HR-NDMM patients. Secondary Hypotheses: Isa-VRD will lead to higher overall response rates (ORR), deeper responses, and improved progression-free survival (PFS) and overall survival (OS). The safety profile of Isa-VRD will be manageable and consistent with the known safety profiles of its individual components.

Timeline

Start

2026-01-30

Primary completion

2028-07

Completion

2029-01

Publications

• Background Davies FE, Pawlyn C, Usmani SZ, San-Miguel JF, Einsele H, Boyle EM, Corre J, Auclair D, Cho HJ, Lonial S, Sonneveld P, Stewart AK, Bergsagel PL, Kaiser MF, Weisel K, Keats JJ, Mikhael JR, Morgan KE, Ghobrial IM, Orlowski RZ, Landgren CO, Gay F, Caers J, Chng WJ, Chari A, Walker BA, Kumar SK, Costa LJ, Anderson KC, Morgan GJ. Perspectives on the Risk-Stratified Treatment of Multiple Myeloma. Blood Cancer Discov. 2022 Jul 6;3(4):273-284. doi: 10.1158/2643-3230.BCD-21-0205.
• Background Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hajek R, Liu Z, Minarik J, Moreau P, Romejko-Jarosinska J, Spicka I, Vorobyev VI, Besemer B, Ishida T, Janowski W, Kalayoglu-Besisik S, Parmar G, Robak P, Zamagni E, Goldschmidt H, Martin TG, Manier S, Mohty M, Oprea C, Bregeault MF, Mace S, Berthou C, Bregman D, Klippel Z, Orlowski RZ; IMROZ Study Group. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Oct 31;391(17):1597-1609. doi: 10.1056/NEJMoa2400712. Epub 2024 Jun 3.
• Background Leleu X, Hulin C, Lambert J, Bobin A, Perrot A, Karlin L, Roussel M, Montes L, Cherel B, Chalopin T, Slama B, Chretien ML, Laribi K, Dingremont C, Roul C, Mariette C, Rigaudeau S, Calmettes C, Dib M, Tiab M, Vincent L, Delaunay J, Santagostino A, Macro M, Bourgeois E, Orsini-Piocelle F, Gay J, Bareau B, Bigot N, Vergez F, Lebreton P, Tabrizi R, Waultier-Rascalou A, Frenzel L, Le Calloch R, Chalayer E, Braun T, Lachenal F, Corm S, Kennel C, Belkhir R, Blade JS, Joly B, Richez-Olivier V, Gardeney H, Demarquette H, Robu-Cretu D, Garderet L, Newinger-Porte M, Kasmi A, Royer B, Decaux O, Arnulf B, Belhadj K, Touzeau C, Mohty M, Manier S, Moreau P, Avet-Loiseau H, Corre J, Facon T. Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial. Nat Med. 2024 Aug;30(8):2235-2241. doi: 10.1038/s41591-024-03050-2. Epub 2024 Jun 3.
• Background Deckert J, Wetzel MC, Bartle LM, Skaletskaya A, Goldmacher VS, Vallee F, Zhou-Liu Q, Ferrari P, Pouzieux S, Lahoute C, Dumontet C, Plesa A, Chiron M, Lejeune P, Chittenden T, Park PU, Blanc V. SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin Cancer Res. 2014 Sep 1;20(17):4574-83. doi: 10.1158/1078-0432.CCR-14-0695. Epub 2014 Jul 1.

Drugs

Indications