Evaluation of Pharmacokinetics, Safety, and Preliminary Efficacy of Isatuximab in Chinese Patients With Relapsed and/or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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Primary Objective: To evaluate the pharmacokinetics (PK) of isatuximab. Secondary Objectives: To evaluate the safety and tolerability of isatuximab. To assess the preliminary antitumor effect of isatuximab. To evaluate the immunogenicity of isatuximab.

Detailed Description
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The duration of the study for an individual patient will include a screening period of up to 21 days, a treatment period of repeated 28-day cycles, and a follow-up period. End of treatment visit will be done at 30 (±7) days after last treatment.

Official Title
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An Open-label, Multi-center Study to Evaluate the Pharmacokinetics, Safety, and Preliminary Efficacy of Isatuximab in Chinese Patients With Relapsed and/or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Isatuximab SAR650984


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Known diagnosis of symptomatic multiple myeloma. At least 2 prior lines of therapies which must include treatment with at least 1 of an immunomodulatory drug (IMiD) or a proteasome inhibitor (PI). The patients must have received an IMiD or a PI for ≥2 cycles or ≥2 months of treatment. Patients must have been responsive to at least 1 prior line of therapy (minimal response or better). Refractory to the most recently received IMiD or PI included therapy (ie, patients must have progressed during or within 60 days of completion of treatment with IMiD or PI). For patients who have received more than 1 type of IMiD or PI, their disease must be refractory to the most recent one. Measurable disease defined as at least 1 of the following: Serum M-protein ≥0.5 g/dL (≥5 g/L); Urine M-protein ≥200 mg/24 hours. Written informed consent. Exclusion criteria: <18 years old. Eastern Cooperative Oncology Group (ECOG) performance status >2. Life expectancy of less than 3 months. Pretreated with any anticluster of differentiation (CD) 38 agent. Concurrent plasma cell leukemia. Known amyloidosis. Disease measurable only by serum free light chain (FLC) analysis. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isatuximab<br>Administered intravenously every week in Cycle 1 (4 weeks) followed by every 2 weeks (Q2W) in subsequent cycles. | Drug: Isatuximab SAR650984<br>* Pharmaceutical form: Concentrate for solution Route of administration: Intravenous<br>* Other names: Sarclisa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK: Cmax | To evaluate the maximum observed concentration (Cmax) | Cycle 1, up to 168 hours after start of infusion | 
| Assessment of PK: tmax | To evaluate the time to reach Cmax (tmax) | Cycle 1, up to 168 hours after start of infusion | 
| Assessment of PK: AUC0-168h | To evaluate area under the plasma concentration versus time curve over the dosing interval (AUC0-168h) | Cycle 1, up to 168 hours after start of infusion | 
| Assessment of PK: Ceoi | To evaluate the concentration observed at the end of an IV infusion (Ceoi) | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1; Cycle duration is 28 days | 
| Assessment of PK: Ctrough | To evaluate concentration observed just before investigational medicinal product (IMP) administration during repeated dosing (Ctrough) | Up to approximately 40 weeks (Cycle 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Treatment Emergent Adverse Events (TEAEs)/Serious Adverse Events (SAE) based on standard and systematic assessment including infusion associated reactions (IARs), laboratory test abnormalities, vital signs and ECOG performance status | Up to 30 days after the last IMP administration | 
| Anti-tumor activity: Overall response (ORR) | Proportion of patients achieving: stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to International Myeloma Working Group (IMWG 2016) criteria | Up to 12 months after last patient treated | 
| Anti-Tumor Activity: Duration of response (DOR) | Time from the date of the first determined response to the date of subsequent determined progressive disease or death, whichever happens earlier | Up to 12 months after last patient treated | 
| Anti-Tumor Activity: Time to progression (TTP) | Time interval from the date of first IMP administration to the date of the first assessed disease progression using IMWG criteria | Up to 12 months after last patient treated | 
| Anti-Tumor Activity: Progression free survival (PFS) | Time interval from the date of first IMP administration to the date of the first documentation of disease progression or death due to any cause, whichever comes first | Up to 12 months after last patient treated | 
| Anti-Tumor Activity: Overall survival (OS) | Time interval from the date of first IMP administration to death due to any cause | Up to 12 months after last patient treated | 
| Immunogenicity | To evaluate the presence of antidrug antibodies (ADA) to isatuximab | Up to 13 months (10 cycles + 3 months) after last patient treated | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-CD38 monoclonal antibody