Study of Isatuximab Combined With Bortezomib + Cyclophosphamide + Dexamethasone (VCD) and Bortezomib + Lenalidomide + Dexamethasone (VRD) in Newly Diagnosed Multiple Myeloma (MM) Non Eligible for Transplant or No Intent for Immediate Transplantation

Summary

Primary Objectives: * VCDI cohort: * To determine the maximum tolerated dose (MTD) and recommended dose (RD) of SAR650984 isatuximab when administered in combination with bortezomib (Velcade®) , cyclophosphamide, and dexamethasone (VCDI) based on the dose-limiting toxicity(ies) (DLTs) observed in patients with newly diagnosed multiple myeloma non-eligible for transplantation * To evaluate safety and preliminary efficacy (overall response rate and complete response rate) of isatuximab administered at the selected dose in combination with bortezomib based regimin VCDI according to IMWG criteria. * VRDI Part A cohort and Part B cohort: * To evaluate the preliminary efficacy (complete response \[CR\] rate) of isatuximab administered at the selected dose in combination with bortezomib based regimen: VRDI, (bortezomib, lenalidomide, dexamethasone) according to IMWG criteria in adult patients with newly diagnosed MM non eligible for transplantation or no intent for immediate transplantation. Secondary Objectives: * VCDI cohort: * To characterize the overall safety profile of SAR650984 in combination with VCD regimen, including cumulative toxicities. * To characterize the pharmacokinetic (PK) profile of SAR650984/isatuximab and each combination drug in VCDI regimen. * To evaluate the immunogenicity of SAR650984 in combination treatments. * To evaluate the preliminary efficacy of VCDI regimen in terms of duration of response and progression-free survival. * To assess the relationship between clinical effects (adverse event \[AE\] and/or tumor response) and CD38 receptor density. * VRDI Part A cohort and Part B cohort: * To characterize the overall safety profile of isatuximab in combination with VRD regimen. * To evaluate the infusion duration (only applicable for VRDI Part B cohort) * To characterize the PK profile of isatuximab and each combination drug in VRDI regimen. * To evaluate the immunogenicity of isatuximab in combination treatments. * To evaluate the preliminary efficacy of VRDI regimen in terms of ORR, DOR, and PFS. * To evaluate the impact of M protein measurement without isatuximab interference (via the SEBIA HYDRASHIFT 2/4 isatuximab IFE test) on CR and BOR assessment. * To assess the relationship between clinical effects (AE and/or tumor response) and CD38 receptor density (only applicable for VRDI Part A cohort). * To assess MRD negativity rate in patients achieving a CR or VGPR and explore correlation with clinical outcome.

Timeline

Start

2015-09-30

Primary completion

2022-01-28

Completion

2024-01-22

Publications

• Ocio EM, Perrot A, Moreau P, Mateos MV, Bringhen S, Martinez-Lopez J, Karlin L, Oprea C, Li Y, Kodas E, San-Miguel J. Plain language summary of a study on 30-minute intravenous infusion of isatuximab in people with newly diagnosed multiple myeloma. Future Oncol. 2026 May;22(11):1235-1246. doi: 10.1080/14796694.2026.2652723. Epub 2026 Apr 27.
• Ocio EM, Perrot A, Bories P, San-Miguel JF, Blau IW, Karlin L, Martinez-Lopez J, Wang SY, Bringhen S, Marcatti M, Mateos MV, Rodriguez-Otero P, Oliva S, Nogai A, Le Roux N, Dong L, Mace S, Gassiot M, Fitzmaurice T, Oprea C, Moreau P. Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. Leukemia. 2023 Jul;37(7):1521-1529. doi: 10.1038/s41375-023-01936-7. Epub 2023 Jun 14.

Drugs

Indications