Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients

Study Overview
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Brief Summary
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Primary Objectives: Phase I: To evaluate safety and tolerability of isatuximab in Japanese patients with relapsed and refractory multiple myeloma. Phase II: To evaluate efficacy of isatuximab at recommended dose and to further evaluate the overall response rate (ORR) of isatuximab in Japanese patients with relapsed and refractory multiple myeloma. Secondary Objectives: To evaluate the safety including immunogenicity of isatuximab. The severity, frequency and incidence of all adverse events will be assessed. To evaluate the pharmacokinetic (PK) profile of isatuximab in the proposed dosing schedule. To assess the efficacy using International Myeloma Working Group (IMWG) uniform response criteria. To assess the relationship between baseline CD38 receptor density on multiple myeloma cells and efficacy.

Detailed Description
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The study duration for an individual patient will include a screening period for inclusion of up to 21 days, the treatment period consisting of 28 day cycles and a follow-up period. Treatment with isatuximab may continue until disease progression, unacceptable adverse event or other reason for discontinuation.

Official Title
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A Phase I/II Study of Isatuximab (Anti-CD38 mAb) Administered as a Single Agent in Japanese Patients With Relapsed and 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: Males or females, age 20 years or older. Patient must have a known diagnosis of symptomatic multiple myeloma. Patients must have received at least 3 prior lines of therapies OR Patients whose disease is double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI). Subject must have been responsive (ie, minimal response [MR] or better) to at least one prior line of therapy. Refractory to the most recently received IMiD or PI included therapy. Patients with measurable disease defined as at least one of the following: IgG Type: Serum M-protein ≥1 g/dL (≥10 g/L); IgA and D Type: Serum M-protein, quantification should be performed; Urine M-protein ≥200 mg/24 hours. Patients with a Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Exclusion criteria: Patients treated with any anti-CD38 agent. Diagnosed or treated for another malignancy within 5 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. Prior anticancer therapy (chemotherapy, targeted agents, immunotherapy) within 21 days prior to the first drug infusion unless otherwise specified below: Alkylating agents (eg, Melphalan) within 28 days prior to the first dose of study treatment. Steroids treatment (eg, prednisone >10 mg/day orally or equivalent except patients being treated for adrenal insufficiency/replacement therapy or treated for inhalation corticosteroids) within 14 days prior to the first dose of study treatment. Participated in another clinical trial within 30 days prior to the first dose of study treatment. Patients treated with systemic radiation therapy within 4 weeks prior to the first dose of study treatment OR Localized radiation therapy within 1 week prior to the first dose of study treatment. Major surgical procedure within 4 weeks prior to the first dose of study treatment. Any toxicity Grade ≥2 (excluding alopecia, neutropenia or neuropathy) related to any prior anti-cancer therapy according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Neuropathy Grade ≥3 or painful peripheral neuropathy Grade ≥2. History of significant cardiovascular disease unless the disease within the past 6 months is well-controlled. Previously received an allogenic stem cell transplant. Diagnosed Crow-Fukase (POEMS) syndrome OR plasma cell leukemia. Patients with known or suspected amyloidosis. Patients with Waldenstrom's macroglobulinemia OR Multiple myeloma IgM subtype. Patients with active infection. Known human immunodeficiency virus (HIV) or active hepatitis B or C viral infection. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation. Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results. Hypersensitivity or history of intolerance to boron or mannitol, sucrose, histidine (as base and hydrochloride salt) and polysorbate 80 or any of the components of study therapy that are not amenable to pre-medication with steroids and H2 blockers or would prohibit further treatment with these agents. 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: 20 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>Isatuximab will be administered intravenously (IV) once every week (QW) for 4 weeks followed by once every other week (Q2W) | Drug: Isatuximab SAR650984<br>* Pharmaceutical form: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 |
| --- | --- | --- |
| Phase I: Dose Limiting Toxicities (DLT) |  | 28 days | 
| Phase II: Overall Response Rate (ORR) |  | 4 months after the date of the first dose of the last patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with Treatment-emergent adverse events/serious adverse events (TEAE/SAE) |  | Up to approximately 30 days after the last study treatment | 
| Clinical Benefit Rate (CBR) |  | 4 months after the date of the first dose of the last patient | 
| Overall Survival (OS) |  | months after the date of the first dose of the last patient | 
| Progression Free Survival (PFS) |  | 12 months after the date of the first dose of the last patient | 
| Duration of Response (DOR) |  | 12 months after the date of the first dose of the last patient | 
| Time to Progression (TTP) |  | 12 months after the date of the first dose of the last patient | 
| Assessment of PK parameter: Concentration observed at the end of an intravenous infusion (Ceoi) |  | Up to approximately 30 days after the last study treatment | 
| Assessment of PK parameter: Maximum observed concentration (Cmax) |  | Up to approximately 30 days after the last study treatment | 
| Assessment of PK parameter: Time to reach the maximum concentration (Tmax) |  | Up to approximately 30 days after the last study treatment | 
| Assessment of PK parameter: Concentrations just before drug infusion (Ctrough) |  | Up to approximately 30 days after the last study treatment | 
| Assessment of PK parameter: AUC over the dosing interval |  | Up to approximately 30 days after the last study treatment | 
| CD38 receptor density levels |  | Baseline | 
| Level of anti-drug antibodies (ADA) |  | Up to approximately 60 days after the last study treatment | 

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