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

Conditions: Plasma Cell Myeloma

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.

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.

Eligibility criteria:
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 (\ 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.

Keywords: anti-cd38 monoclonal antibody