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

A Dose Escalation, Safety, Pharmacokinetic, Pharmacodynamic and Preliminary Efficacy Study of SAR650984 (Isatuximab) Administered Intravenously in Combination With Bortezomib - Based Regimens in Adult Patients With Newly Diagnosed Multiple Myeloma Non Eligible for Transplantation or No Intent for Immediate Transplantation

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.

The duration of the study for an individual patient will include:

• A period to assess eligibility (screening or baseline period) of up to 3 weeks for VCDI cohort, up to 28 days for VRDI cohort;
• for patients in the VCDI cohort: a treatment period including up to 12 induction treatment cycles (50-week duration).
• for patients in the VRDI cohort: a treatment period including up to 4 induction cycles (24 week duration).
• Following induction, both cohorts have maintenance periods consisting of 4 week cycles until progression, unacceptable AE, or patient willingness to discontinue and an end-of-treatment visit at least 30 days following the last administration of treatment.
• Patients that discontinue therapy for reasons other than progression will have follow-up visits until progression or until the patient receives another anticancer therapy, whichever is earlier.

Inclusion criteria:

• Newly diagnosed patients with measurable multiple myeloma defined as at least one of the following:

  • Serum M protein ≥1 g/dL (≥10 g/L).
  • Urine M protein ≥200 mg/24 hours.
  • Serum free light chain (sFLC) assay: involved free light chain assay ≥10 mg/dL (≥100 mg/L) and an abnormal sFLC ratio (<0.26 or >1.65).

• Patients with ultra-high risk smoldering multiple myeloma fulfilling the International Myeloma Working Group criteria are eligible.

• Patient is not eligible for transplant.

• Patient with no intent for immediate transplant as per investigator's decision are also eligible for VRDI Part B cohort only.

Exclusion criteria:

• Eastern Cooperative Oncology Group performance status >2.
• Poor bone marrow reserve.
• Poor organ function.

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