A Study to Investigate the Clinical Benefit of Isatuximab in Combination With Bortezomib, Lenalidomide and Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant

A Phase 3 Randomized, Open-label, Multicenter Study Assessing the Clinical Benefit of Isatuximab (SAR650984) in Combination With Bortezomib (Velcade®), Lenalidomide and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant

Primary Objective:

-To demonstrate the benefit of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone in the prolongation of progression free survival (PFS) as compared to bortezomib, lenalidomide, and dexamethasone, in participants with newly diagnosed multiple myeloma (NDMM) not eligible for transplant.

Secondary Objectives:

• To evaluate in both randomized (isatuximab, bortezomib, lenalidomide and dexamethasone combination (IVRd) and bortezomib, lenalidomide and dexamethasone combination (VRd)) arms:
• Complete response (CR) rate, as defined by the International Myeloma Working Group (IMWG) criteria.
• Minimal residual disease (MRD) negativity rate in participants with CR.
• Very good partial response or better rate, as defined by the IMWG criteria.
• Overall survival (OS).
• To evaluate the overall response rate (ORR) as per IMWG criteria.
• To evaluate the time to progression (TTP) overall and by MRD status.
• To evaluate PFS by MRD status.
• To evaluate the duration of response (DOR) overall and by MRD status.
• To evaluate time to first response (TT1R).
• To evaluate time to best response (TTBR).
• To evaluate progression-free survival on next line of therapy (PFS2).
• To evaluate the sustained MRD negativity >12 months rate.
• To evaluate safety.
• To determine the pharmacokinetic (PK) profile of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (IVRd arm only).
• To evaluate the immunogenicity of isatuximab in participants receiving isatuximab (IVRd and crossover arms).
• To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.

The duration of the study for each participant will include a screening period of up to 4 weeks, an induction period of 24 weeks (4 cycles with a duration of 42 ± 3 days), a continuous treatment period and a crossover period (when applicable). The cycle duration is 28 ± 3 days during the continuous treatment and crossover periods.

Inclusion Criteria:

Inclusion criteria :

• Multiple myeloma (IMWG criteria).
• Newly diagnosed multiple myeloma not eligible for transplant due to age (≥ 65 years) or participants < 65 years with comorbidities impacting possibility of transplant.
• Evidence of measurable disease.
• Written informed consent.

Exclusion criteria:

• Age < 18 years.
• Prior treatment for multiple myeloma.
• Any other prior or ongoing disease/health conditions incompatible with the study objectives.
• Organ function values not met.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ( PS) > 2.
• Hypersensitivity to the study medications.
• Pregnant, breastfeeding, or woman of child bearing potential unwilling to use recommended contraception methods.
• Male participants who disagree to follow the study contraceptive counseling.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.