Hematological Malignancy
Conditions
Keywords
Anti-CD38 monoclonal antibody
Brief summary
Primary Objective: Phase 1: To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984 (Isatuximab). Phase 2 (stage 1): To evaluate the activity of single-agent Isatuximab at different doses/schedules and to select dose and regimen to further evaluate the overall response rate (ORR) of Isatuximab as single agent or in combination with dexamethasone. Phase 2 (stage 2): To evaluate the activity in terms of overall response rate (ORR) of Isatuximab at the selected dose/schedule from stage1, as single agent (ISA arm) and in combination with dexamethasone (ISAdex arm). Secondary Objectives: Phase 1: * To characterize the global safety profile including cumulative toxicities. * To evaluate the pharmacokinetic (PK) profile of Isatuximab in the proposed dosing schedule(s). * To assess the pharmacodynamics (PD), immune response, and preliminary disease response. Phase 2 (stage 1): to evaluate the following objectives for Isatuximab as single agent: * Safety * Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival. Phase 2 (stage 2): to evaluate the following objectives in each arm (ISA and ISAdex): * Safety * Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival. * Participant-reported changes in health-related quality of life, symptoms of multiple myeloma and generic health status. * Pharmacokinetic profile of Isatuximab. * Immunogenicity of Isatuximab. * Investigate the relationship between CD38 receptor density and CD38 receptor occupancy (Stage 1 only) on multiple myeloma cells and parameters of clinical response.
Detailed description
The Phase 1 study duration for an individual participant included a screening period for inclusion of up to 2 weeks, treatment with Isatuximab QW (every week) or Q2W (every 2 weeks) unless discontinued earlier due to safety or disease progression. Participants were followed for a minimum of 30 days following the last use of study drug or more than 30 days in case of unresolved toxicity, or up to initiation of another anticancer treatment. The Phase 2 study duration for an individual participant included a screening period for inclusion of up to 3 weeks, then a treatment period and a follow up period. Treatment was continued until disease progression, unacceptable adverse reactions or other reasons for discontinuation. Participants were followed every 3 months following the last use of study drug until death or study cutoff, whichever came first.
Interventions
Pharmaceutical form: solution for infusion Route of administration: intravenous
DRUGDexamethasone
Pharmaceutical form: solution for infusion Route of administration: intravenous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Phase 1: * For dose escalation cohorts, participants with confirmed selected CD38+ hematological malignancies as specified below who had progressed on after standard therapy or for whom there was no effective standard therapy (refractory/relapsed participants). B-cell Non-Hodgkin-lymphoma/leukemia (NHL) participants with at least 1 measurable lesion. Multiple myeloma (MM) participants with measurable M-protein serum and/or 24-hour urine. Acute myeloid leukemia (AML) participants, all types except M3 based on French-American-British (FAB) classification. Acute Lymphoblastic Leukemia (B-cell ALL) participants. Chronic lymphocytic leukemia (CLL) participants. * For expansion cohorts, participants with relapsed/refractory MM with measurable M-protein (serum M-protein of \>0.5 g/dL and/or urine M-protein of \>200 mg (24-hr urine)) or elevated serum free light chains (FLC) \>10 mg/dL with abnormal FLC ratio) who had progressed on or after standard therapy that included an Immunomodulatory drug (IMiD) and a proteasome inhibitor and who met the protocol defined criteria for standard risk or high risk. Phase 2: * Participants had a known diagnosis of multiple myeloma with evidence of measurable disease, and have evidence of disease progression based on International Myeloma Working Group (IMWG) criteria: Serum M-protein ≥1 g/dL, or urine M-protein \>=200 mg/24 hours or in the absence of measurable m-protein, serum FLC \>=10 mg/dL, and abnormal serum immunoglobulin kappa lambda FLC ratio (\<0.26 or \>1.65). * Participants who received at least three prior lines of therapy for MM and had treatment with an IMiD (for \>=2 cycles or \>=2 months of treatment) and a proteasome inhibitor (PI) (for \>=2 cycles or \>=2 months of treatment) OR participants whose disease was double refractory to an IMiD and a PI. For participants who had received more than 1 type of IMiD and PI, their disease must be refractory to the most recent one. * Participants who had achieved a minimal response or better to at least one prior line of therapy. * Participants who had received an alkylating agent (\>=2 cycles or \>=2 months) either alone or in combination with other MM treatments. * Stage 2 only: Participants who had evidence of disease progression on or after the most recent prior regimen based on IMWG criteria.
Exclusion criteria
Phase 1: * Karnofsky performance status \<60 * Poor bone marrow reserve * Poor organ function * Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that was not amenable to pre-medication with steroids and H2 blockers * Any serious active disease (including clinically significant infection that was chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, interfered with the safety, the compliance with the study or with the interpretation of the results * 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 Phase 2: * Participants with multiple myeloma immunoglobulin M (IgM) subtype * Previous treatment with any anti-CD38 therapy * Participants with concurrent plasma cell leukemia * Participants with known or suspected amyloidosis * Karnofsky performance status \<60 (stage 1)/Eastern Cooperative Oncology Group (ECOG) Performance status \>2 (stage 2). * Poor bone marrow reserve * Poor organ function * Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that was not amenable to pre-medication with steroids and H2 blockers * Any serious active disease (including clinically significant infection that was chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, interfered with the safety, the compliance with the study or with the interpretation of the results * Any severe underlying medical conditions including presence of laboratory abnormalities, which impaired the ability to participate in the study or the interpretation of its results The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From Baseline up to 30 days after the last dose (maximum duration: 120 weeks ) | Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment. |
| Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Day 1 of Cycle 1 up to Day 14 of Cycle 2 | DLTs were assessed using the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03. DLTs were defined as any Grade 3 or higher non-hematological toxicity (with the exception of allergic reaction/hypersensitivity), Grade 4 neutropenia and/or Grade 4 thrombocytopenia lasting longer than 5 days, attributed to isatuximab. Any other toxicity that the Investigator and the Sponsor deemed to be dose-limiting, regardless of the grade, was also considered as DLT. |
| Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria | From the date of randomization until disease progression or death or data cut-off (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for Stage 1b arm) | OR defined as participants with stringent complete response (sCR) or complete response (CR) or very good partial response (VGPR) or partial response (PR) . Based on IMWG, CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and \<=5% plasma cells in bone marrow; sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; PR: \>=50% reduction of serum M-Protein and reduction in urinary M-protein by \>=90% or to \<200 mg/24 hours; \>=50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a \>=50% reduction in plasma cells in place of M-protein if present at baseline. |
| Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria | From the date of randomization to date of death from any cause (maximum duration: 97 weeks) | OR: participants with sCR or CR or VGPR or PR. As per updated IMWG, CR: Negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \<=5% plasma cells in bone marrow; normal FLC ratio of 0.26-1.65 in participants with only FLC disease; sCR: CR and normal FLC ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours, \>90% decrease in the difference between involved and uninvolved FLC levels; PR: \>=50% reduction of serum M-Protein and reduction in urinary M-protein by \>=90% or to \<200 mg/24 hours; \>=50% decrease in the difference between involved and uninvolved FLC levels in place of M-protein criteria or \>=50% reduction in plasma cells in place of M-protein if present at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion | Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). |
| PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 336 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 336 hr post-infusion | Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). |
| Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | Cycle 1 Day 1 | Serum/plasma markers included: tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1-β), interleukin 6 (IL-6) and interferon-gamma (IFN-Gamma). Due to change in planned analysis, data for high-sensitivity C-reactive protein (hs-CRP) and CD38 was not collected and analyzed. |
| Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Up to 120 weeks | ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 1) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment. |
| Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | From the date of randomization to the date of first documentation of progression or death (due to any cause) (maximum duration: 120 weeks) | OR defined as participants with complete response (CR) or partial response (PR) as best overall response (BOR). Clinical benefit: participants with minimal response (MR) or better as BOR. BOR: best sequential response from start of treatment through the entire study excluding any time point following start of other treatment. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, \<5% plasma cells in bone marrow aspirates, no increase in size or number of lytic bone lesions. PR: \>=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by \>=90% or \<200mg, \>=50% reduction in size/number of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions. MR: 25 to 49% reduction in serum M-protein, 50-89% reduction in 24h urine M-protein, 25-49% reduction in size of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions. |
| Clinical Assessment: Phase 1: Duration of Response (DOR) | From the date of first response to the date of first documentation of progression or death (due to any cause) (maximum duration: 120 weeks) | DOR: time from first response (PR or better) to first documented tumor progression/death. Progression as per EBMT: \>25% increase in serum monoclonal paraprotein level, which must also be an absolute increase of \>= 5 g/l: confirmed by \>=1 repeated investigation; \>25% increase in 24h urinary light chain excretion, which must also be an absolute increase of \>=200 mg/24 h:confirmed by \>=1 repeated investigation; \>25% increase in plasma cells in a bone marrow aspirate/on trephine biopsy, which must also be an absolute increase of \>= 10%; definite increase in size of existing bone lesions/soft tissue plasmacytomas; development of new bone lesions/soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium \>11·5 mg/dl or 2·8 mmol/l) not attributable to any other cause. PR: \>=50% reduction of serum M-protein, reduction in 24h urinary M-protein by \>=90% or \<200mg, \>=50% reduction in size/number of soft tissue plasmacytomas, no increase in size/number of lytic bone lesions. |
| Clinical Assessment: Phase 1: Time to First Response (TTR) | From the date of first dose administration to the date of first response or death (due to any cause) (maximum duration: 120 weeks) | TTR was defined as the time from first dose of isatuximab to first response (PR or better). PR: \>=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by \>=90% or \<200mg, \>=50% reduction in size/number of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions. |
| Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky Performance Status)-Shift From Baseline Value to Best Value During Treatment | At baseline, during treatment (Day 1 up to 120 weeks) | ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest \<50% of waking hours; 3=Bed rest/sitting \>50% of waking hours; 4=Bedridden or unable to care for self, where lower score indicated good performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the best values (categorized as: Baseline ECOG 1, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 1) are reported. |
| Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment | At baseline, during treatment (up to 120 weeks) | ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest \<50% of waking hours; 3=Bed rest/sitting\>50% of waking hours; 4=Bedridden or unable to care for self, where higher score indicated worst performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the worst values (categorized as: Baseline ECOG 0, During Treatment ECOG 1; Baseline ECOG 2, During Treatment ECOG 1; Baseline ECOG 0, During Treatment ECOG 2; Baseline ECOG 1, During Treatment ECOG 2; Baseline ECOG 0, During Treatment ECOG 3; Baseline ECOG 1, During Treatment ECOG 3; Baseline ECOG 2, During Treatment ECOG 3) are reported. |
| Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From Baseline up to 30 days after the last dose (maximum duration: 414 weeks for Stage 1a and 92 weeks for Stage 1b) | Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment. |
| Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From Baseline up to 30 days after the last dose (maximum duration: 301 weeks) | AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment. |
| Phase 2 Stage 1: Duration of Response | From the date of first response until disease progression or death or data cut-off (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm) | DOR:Time from date of 1st IAC determined response (\>= PR) that was subsequently confirmed, to date of first IAC determined PD/death, whichever happened earlier. updated IMWG criteria- PR:\>=50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or a \>=50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a \>=50% reduction in size of soft tissue plasmacytomas; PD: Increase of 25% from lowest response value in any of following: Serum M-protein \>=0.5 g/dL absolute increase and/or urine M-protein \>=200 mg/24 hours absolute increase and/or \>10 mg/dL absolute increase in difference between involved and uninvolved FLC levels, \>=10% bone marrow plasma cells (PCs), development of new bone lesions/soft tissue plasmacytomas or definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium \>11·5 mg/dl) attributed to PC proliferation disorder. |
| Phase 2 Stage 2: Duration of Response | From the date of first response until disease progression or death or data cut-off (maximum duration: 97 weeks) | DOR: Time from date of 1st IAC determined response (\>= PR) that was subsequently confirmed, to date of 1st IAC determined PD or death, whichever happened earlier. As per updated IMWG criteria-PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. ≥50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline ≥50% reduction in size of soft tissue plasmacytomas; PD: Increase of \>25% from lowest response value in any one of following: Serum M-component (absolute increase must be \>0.5 g/dL)4 and/or Urine M-component (absolute increase must be \>200 mg/24 h) and/or \>10 mg/dL absolute increase in difference between involved and uninvolved FLC levels, \>=10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) attributed solely to plasma cell proliferative disorder. |
| Phase 2 Stage 1: Percentage of Participants With Clinical Benefit | From the date of randomization to the date of first documentation of progression or death (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm) | Clinical benefit: participants with sCR, CR, VGPR, PR or MR as per IMWG criteria, determined by IAC. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytomas,\<5% PCs in bone marrow aspirates. sCR: CR + normal FLC ratio (0.26-1.65), absence of clonal cells in bone marrow biopsy. VGPR: serum & urine M-component detectable by immunofixation, not on electrophoresis/,\>=90% reduction in serum M-component plus urine M-component level \<100mg/24hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours, ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline, ≥50% size reduction in soft tissue plasmacytomas. MR:\>=25 but \<49% reduction in serum M-protein, reduction in 24h urine M-protein by 50-89%, 25-49% size reduction in soft tissue plasmacytomas. |
| Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 and Cycle 3 Day 1: At the end of infusion | Ceoi was defined as the plasma concentration of Isatuximab at end of infusion. Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). Analysis was performed on PK population: participants who gave informed consent, received at least one dose (even if incomplete) of isatuximab, had an assessable PK parameter. |
| Phase 2 Stage 1: Progression Free Survival (PFS) | From the date of the first dose administration until progression or death, whichever occurred first (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm) | PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression (PD) or date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of \> 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be \> 0.5 g/dL), Urine M-component and/or (the absolute increase must be \> 200 mg/24 h), \> 10mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, \>10% absolute percentage of bone marrow plasma cell, definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method. |
| Phase 2 Stage 2: Progression Free Survival | From the date of the first dose administration until progression or death, whichever occurred first (maximum duration: 97 weeks) | PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression or the date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of \>25% from lowest response value in any one of the following: Serum M-component (the absolute increase must be \>0.5 g/dL)4 and/or Urine M-component (the absolute increase must be \>200 mg/24 h) and/or \>10 mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, ≥10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method. |
| Phase 2 Stage 1: Overall Survival (OS) | From the date of randomization to date of death from any cause (maximum duration 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm) | OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method. |
| Phase 2 Stage 2: Overall Survival | From the date of randomization to date of death from any cause (maximum duration: 97 weeks) | OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method. |
| Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10 and End of Treatment (EOT: anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm) | EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & other single items. For each item, high score = high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant. |
| Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10 and EOT (anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm) | EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with MM. It has 4 subscales: body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). Disease symptoms subscale used 4-point scale ranged from 1= 'Not at All' to 4= 'Very Much'. Scores were averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL. |
| Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Baseline, Day 1 of Cycles 4, 7, 10, 13, 16, 19, and EOT (anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm) | EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. |
| Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 1 Week Interval | Pre-dose, at the end of infusion, 1 hour and 168 hours post dose on Day 1 of Cycle 1 | — |
| Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 2 Weeks Interval | Cycle 1, Day 1: pre-dose, at the end of infusion, 168 and 336 hours post-infusion | — |
| Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 4 Weeks Interval | Cycle 1, Day 1: pre-dose, at the end of infusion, 168, 336, and 672 hours post-infusion | — |
| Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough) | At Days 7, 14 and 28 | — |
| Pharmacokinetic Assessment: Phase 2 Stage 2: Accumulation Ratio of Isatuximab Based on Ctrough | Cycle 2, Day 1; Cycle 1, Day 8; Cycle 4, Day 1 | Ctrough is the plasma concentration observed before treatment administration. For 1st category, the accumulation ratio was calculated by dividing Ctrough value of Cycle 2 Day 1 by Cycle 1 Day 8 and for second category, accumulation ratio was calculated by dividing Ctrough value of Cycle 4 Day 1 by Cycle 1 Day 8. |
| Immunogenicity Assessment: Phase 2 Stage 2: Number of Participants With Anti-drug Antibodies to Isatuximab | Up to 97 weeks | ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 2 Stage 2) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment. |
| Phase 2 Stage 2: Percentage of Participants With Clinical Benefit | From the date of randomization to the date of first documentation of progression or death (maximum duration: 97 weeks ) | Clinical benefit:participants with sCR, CR, VGPR, PR or MR, per IMWG criteria, determined by IAC. CR:negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytomas,\<5% plasma cells in bone marrow aspirates,normal FLC ratio(0.26-1.65) in participants with only FLC disease.sCR:CR+normal FLC ratio, absence of clonal cells in bone marrow biopsy.VGPR:serum & urine M-component detectable by immunofixation, not on electrophoresis/,\>=90% reduction in serum M-component plus urine M-component level \<100mg/24h/,\>=90% decrease in difference between involved and uninvolved FLC levels; PR:\>=50% reduction of serum M-protein, reduction in 24h urinary M-protein by \>=90%/\<200mg/24h,\>50% decrease in difference between involved and uninvolved FLC in place of M-protein criteria, \>=50% reduction in size/number of soft tissue plasmacytomas. MR:\>=25 but \<49% reduction in serum M-protein,reduction in 24h urine M-protein by 50-89%, 25-49% reduction in size of soft tissue plasmacytomas |
| PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion | Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). Analysis was performed on PK population. |
| PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion | Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). Analysis was performed on PK population. |
| PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1, 2 and 3 | Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). |
Countries
Argentina, Belgium, Brazil, Chile, Finland, France, Greece, Israel, Italy, Mexico, Peru, Russia, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Study participants were involved in the study from 11 May 2010 at 59 centers in 18 countries. A total of 418 participants were screened, of which 351 participants were enrolled. A total of 67 participants had screen failures due to failure to meet inclusion criteria.
Pre-assignment details
Study consisted 2 phases: Phase 1 and Phase 2. Phase 1 was a dose escalation part of isatuximab to determine maximum tolerated dose (MTD). Phase 2 was conducted for efficacy and safety evaluation of isatuximab with or without dexamethasone. It consisted of 2 stages: Stage 1 (comprised of 1a and 1b) and Stage 2.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W Participants with CD38+ HM, received Isatuximab at any one of the dose \<= 1 mg/kg (i.e. either 0.0001 mg/kg or 0.001 mg/kg or 0.01 mg/kg or 0.03 mg/kg, or 0.1 mg/kg or 0.3 mg/kg or 1 mg/kg) as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal by participant, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks). | 16 |
| Phase 1: Isatuximab 3mg/kg Q2W Participants with CD38+ HM, received Isatuximab 3 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks). | 6 |
| Phase 1: Isatuximab 5 mg/kg Q2W Participants with CD38+ HM, received Isatuximab 5 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks). | 3 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) Participants with CD38+ HM along with participants with standard risk multiple myeloma were included in this arm and, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks). | 26 |
| Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma) Participants with CD38+ HM along with participants with high risk multiple myeloma were included in this arm and, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks). | 18 |
| Phase 1: Isatuximab 10 mg/kg QW Participants with CD38+ HM, received Isatuximab 10 mg/kg, as IV infusion QW, i.e. on Day 1 and 8 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks). | 6 |
| Phase 1: Isatuximab 20 mg/kg Q2W Participants with CD38+ HM, received Isatuximab 20 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks). | 7 |
| Phase 1: Isatuximab 20 mg/kg QW Participants with CD38+ HM, received Isatuximab 20 mg/kg, as IV infusion QW, i.e. on Day 1 and 8 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks). | 7 |
| Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W Participants with multiple Myeloma received Isatuximab 3 mg/kg, as IV infusion on Day 1 and Day 15 of each 28-day cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 414 weeks). | 23 |
| Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W Participants with multiple Myeloma received Isatuximab 10 mg/kg, as IV infusion on Day 1 and Day 15 of each 28-day cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 414 weeks). | 24 |
| Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W Participants with multiple Myeloma received Isatuximab 10 mg/kg, as IV infusion Q2W, i.e. on Day 1 and Day 15 of Cycle 1 and 2 (each cycle 28 days), then every 4 weeks (Q4W), i.e. on Day 1 of each 28-days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 414 weeks). | 25 |
| Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W Participants with multiple Myeloma received Isatuximab 20 mg/kg, as IV infusion QW, i.e. on Day 1, 8, 15 and 22 of Cycle 1 and 2 (each cycle 28 days), then Q2W, i.e. on Day 1 and Day 15 of each 28-days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 92 weeks). | 25 |
| Phase 2 Stage 2: Isatuximab Alone Participants with relapsed or relapsed/refractory multiple myeloma (RRMM), received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator's decision (maximum exposure: 301 weeks). | 109 |
| Phase 2 Stage 2: Isatuximab + Dexamethasone Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles along with dexamethasone: tablet or as IV infusion (40 mg/day for less than \[\<\] 75 years of age; 20 mg/day for greater than or equal to \[\>=\] 75 years of age) on Days 1, 8, 15 and 22 of each 28 days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator's decision (maximum exposure: 301 weeks). | 55 |
| Total | 350 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase 2 Stage 2 (301 Weeks) | Enrolled, but not treated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Phase 2 Stage 2: Isatuximab + Dexamethasone | Phase 2 Stage 2: Isatuximab Alone | Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W | Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W | Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W | Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W | Phase 1: Isatuximab 20 mg/kg QW | Phase 1: Isatuximab 20 mg/kg Q2W | Phase 1: Isatuximab 10 mg/kg QW | Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma) | Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 1: Isatuximab 5 mg/kg Q2W | Phase 1: Isatuximab 3mg/kg Q2W | Phase 1:Isatuximab <=1 mg/kg Q2W |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 9.2 | 66.3 years STANDARD_DEVIATION 8.9 | 66.6 years STANDARD_DEVIATION 8.8 | 61.1 years STANDARD_DEVIATION 10.3 | 61.0 years STANDARD_DEVIATION 7.3 | 63.9 years STANDARD_DEVIATION 8.8 | 63.2 years STANDARD_DEVIATION 8.9 | 60.0 years STANDARD_DEVIATION 8.3 | 63.3 years STANDARD_DEVIATION 10 | 61.7 years STANDARD_DEVIATION 12.7 | 60.8 years STANDARD_DEVIATION 12.6 | 65.0 years STANDARD_DEVIATION 7.2 | 62.0 years STANDARD_DEVIATION 3.5 | 63.5 years STANDARD_DEVIATION 6.2 | 64.9 years STANDARD_DEVIATION 11.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 3 Participants | 5 Participants | 3 Participants | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 35 Participants | 6 Participants | 11 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 6 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 287 Participants | 45 Participants | 91 Participants | 21 Participants | 19 Participants | 19 Participants | 21 Participants | 7 Participants | 6 Participants | 4 Participants | 13 Participants | 20 Participants | 3 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Female | 162 Participants | 26 Participants | 58 Participants | 13 Participants | 7 Participants | 11 Participants | 11 Participants | 3 Participants | 2 Participants | 2 Participants | 9 Participants | 11 Participants | 1 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 188 Participants | 29 Participants | 51 Participants | 12 Participants | 18 Participants | 13 Participants | 12 Participants | 4 Participants | 5 Participants | 4 Participants | 9 Participants | 15 Participants | 2 Participants | 3 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 16 | 1 / 6 | 0 / 3 | 0 / 26 | 2 / 18 | 2 / 6 | 2 / 7 | 0 / 7 | 11 / 23 | 13 / 24 | 11 / 25 | 11 / 25 | 56 / 109 | 25 / 55 |
| other Total, other adverse events | 16 / 16 | 6 / 6 | 3 / 3 | 26 / 26 | 18 / 18 | 6 / 6 | 6 / 7 | 6 / 7 | 22 / 23 | 23 / 24 | 25 / 25 | 24 / 25 | 92 / 109 | 47 / 55 |
| serious Total, serious adverse events | 3 / 16 | 3 / 6 | 1 / 3 | 10 / 26 | 10 / 18 | 3 / 6 | 3 / 7 | 3 / 7 | 13 / 23 | 11 / 24 | 10 / 25 | 9 / 25 | 52 / 109 | 27 / 55 |
Outcome results
Primary
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were assessed using the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03. DLTs were defined as any Grade 3 or higher non-hematological toxicity (with the exception of allergic reaction/hypersensitivity), Grade 4 neutropenia and/or Grade 4 thrombocytopenia lasting longer than 5 days, attributed to isatuximab. Any other toxicity that the Investigator and the Sponsor deemed to be dose-limiting, regardless of the grade, was also considered as DLT.
Time frame: Day 1 of Cycle 1 up to Day 14 of Cycle 2
Population: DLT evaluable population included participants who gave their informed consent, received at least 1 dose of isatuximab during Phase 1 and had a DLT assessment at the end of Cycle 2. Data was planned not to be collected and analyzed for the arm: Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1: Isatuximab 10 mg/kg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1: Isatuximab 20mg/kg Q2W | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1: Isatuximab 20mg/kg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Time frame: From Baseline up to 30 days after the last dose (maximum duration: 120 weeks )
Population: Analysis was performed on AT population which included participants who signed informed consent and received at least 1 dose/even incomplete of isatuximab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 16 Participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 26 Participants |
| Phase 1: Isatuximab 10 mg/kg QW | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 18 Participants |
| Phase 1: Isatuximab 20mg/kg Q2W | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1: Isatuximab 20mg/kg QW | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Phase 1: Isatuximab 20mg/kg QW | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
Primary
Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria
OR defined as participants with stringent complete response (sCR) or complete response (CR) or very good partial response (VGPR) or partial response (PR) . Based on IMWG, CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and \<=5% plasma cells in bone marrow; sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; PR: \>=50% reduction of serum M-Protein and reduction in urinary M-protein by \>=90% or to \<200 mg/24 hours; \>=50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a \>=50% reduction in plasma cells in place of M-protein if present at baseline.
Time frame: From the date of randomization until disease progression or death or data cut-off (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for Stage 1b arm)
Population: Analysis was performed on AT population which included participants who signed informed consent and received at least 1 dose/even incomplete of isatuximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria | 4.3 percentage of participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria | 29.2 percentage of participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria | 20.0 percentage of participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria | 24.0 percentage of participants |
Primary
Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria
OR: participants with sCR or CR or VGPR or PR. As per updated IMWG, CR: Negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \<=5% plasma cells in bone marrow; normal FLC ratio of 0.26-1.65 in participants with only FLC disease; sCR: CR and normal FLC ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours, \>90% decrease in the difference between involved and uninvolved FLC levels; PR: \>=50% reduction of serum M-Protein and reduction in urinary M-protein by \>=90% or to \<200 mg/24 hours; \>=50% decrease in the difference between involved and uninvolved FLC levels in place of M-protein criteria or \>=50% reduction in plasma cells in place of M-protein if present at baseline.
Time frame: From the date of randomization to date of death from any cause (maximum duration: 97 weeks)
Population: Analysis was performed on AT population which included participants who signed informed consent \& received at least 1 dose/even incomplete of isatuximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria | 23.9 percentage of participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria | 43.6 percentage of participants |
Secondary
Clinical Assessment: Phase 1: Duration of Response (DOR)
DOR: time from first response (PR or better) to first documented tumor progression/death. Progression as per EBMT: \>25% increase in serum monoclonal paraprotein level, which must also be an absolute increase of \>= 5 g/l: confirmed by \>=1 repeated investigation; \>25% increase in 24h urinary light chain excretion, which must also be an absolute increase of \>=200 mg/24 h:confirmed by \>=1 repeated investigation; \>25% increase in plasma cells in a bone marrow aspirate/on trephine biopsy, which must also be an absolute increase of \>= 10%; definite increase in size of existing bone lesions/soft tissue plasmacytomas; development of new bone lesions/soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium \>11·5 mg/dl or 2·8 mmol/l) not attributable to any other cause. PR: \>=50% reduction of serum M-protein, reduction in 24h urinary M-protein by \>=90% or \<200mg, \>=50% reduction in size/number of soft tissue plasmacytomas, no increase in size/number of lytic bone lesions.
Time frame: From the date of first response to the date of first documentation of progression or death (due to any cause) (maximum duration: 120 weeks)
Population: Analysis was performed only on subset of participants who had response in Phase 1 and not for the reporting group with no response.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Duration of Response (DOR) | 20.21 months | — |
| Phase 1: Isatuximab 3mg/kg Q2W | Clinical Assessment: Phase 1: Duration of Response (DOR) | 7.16 months | — |
| Phase 1: Isatuximab 5mg/kg Q2W | Clinical Assessment: Phase 1: Duration of Response (DOR) | 5.76 months | Standard Deviation 4.62 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Clinical Assessment: Phase 1: Duration of Response (DOR) | 10.70 months | Standard Deviation 11.25 |
| Phase 1: Isatuximab 10 mg/kg QW | Clinical Assessment: Phase 1: Duration of Response (DOR) | 14.31 months | Standard Deviation 7.5 |
| Phase 1: Isatuximab 20mg/kg Q2W | Clinical Assessment: Phase 1: Duration of Response (DOR) | 3.94 months | — |
| Phase 1: Isatuximab 20mg/kg QW | Clinical Assessment: Phase 1: Duration of Response (DOR) | 8.82 months | Standard Deviation 7.83 |
Secondary
Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky Performance Status)-Shift From Baseline Value to Best Value During Treatment
ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest \<50% of waking hours; 3=Bed rest/sitting \>50% of waking hours; 4=Bedridden or unable to care for self, where lower score indicated good performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the best values (categorized as: Baseline ECOG 1, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 1) are reported.
Time frame: At baseline, during treatment (Day 1 up to 120 weeks)
Population: Analysis was performed on AT population. Data for this outcome measure was planned to be collected and analyzed for a combined arm of overall Phase 1 AT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky Performance Status)-Shift From Baseline Value to Best Value During Treatment | Baseline ECOG 1, During Treatment ECOG 0 | 11 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky Performance Status)-Shift From Baseline Value to Best Value During Treatment | Baseline ECOG 2, During Treatment ECOG 0 | 2 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky Performance Status)-Shift From Baseline Value to Best Value During Treatment | Baseline ECOG 2, During Treatment ECOG 1 | 11 Participants |
Secondary
Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment
ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest \<50% of waking hours; 3=Bed rest/sitting\>50% of waking hours; 4=Bedridden or unable to care for self, where higher score indicated worst performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the worst values (categorized as: Baseline ECOG 0, During Treatment ECOG 1; Baseline ECOG 2, During Treatment ECOG 1; Baseline ECOG 0, During Treatment ECOG 2; Baseline ECOG 1, During Treatment ECOG 2; Baseline ECOG 0, During Treatment ECOG 3; Baseline ECOG 1, During Treatment ECOG 3; Baseline ECOG 2, During Treatment ECOG 3) are reported.
Time frame: At baseline, during treatment (up to 120 weeks)
Population: Analysis was performed on AT population. Data for this outcome measure was planned to be collected and analyzed for a combined arm of overall Phase 1 AT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment | Baseline ECOG 0, During Treatment ECOG 1 | 8 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment | Baseline ECOG 2, During Treatment ECOG 1 | 1 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment | Baseline ECOG 0, During Treatment ECOG 2 | 3 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment | Baseline ECOG 1, During Treatment ECOG 2 | 20 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment | Baseline ECOG 0, During Treatment ECOG 3 | 1 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment | Baseline ECOG 1, During Treatment ECOG 3 | 2 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment | Baseline ECOG 2, During Treatment ECOG 3 | 1 Participants |
Secondary
Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria
OR defined as participants with complete response (CR) or partial response (PR) as best overall response (BOR). Clinical benefit: participants with minimal response (MR) or better as BOR. BOR: best sequential response from start of treatment through the entire study excluding any time point following start of other treatment. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, \<5% plasma cells in bone marrow aspirates, no increase in size or number of lytic bone lesions. PR: \>=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by \>=90% or \<200mg, \>=50% reduction in size/number of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions. MR: 25 to 49% reduction in serum M-protein, 50-89% reduction in 24h urine M-protein, 25-49% reduction in size of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions.
Time frame: From the date of randomization to the date of first documentation of progression or death (due to any cause) (maximum duration: 120 weeks)
Population: Analysis was performed on all-treated population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | OR | 33.3 percentage of participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | Clinical benefit | 33.3 percentage of participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | OR | 0 percentage of participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | Clinical benefit | 20.0 percentage of participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | OR | 33.3 percentage of participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | Clinical benefit | 33.3 percentage of participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | OR | 28.0 percentage of participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | Clinical benefit | 28.0 percentage of participants |
| Phase 1: Isatuximab 10 mg/kg QW | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | OR | 16.7 percentage of participants |
| Phase 1: Isatuximab 10 mg/kg QW | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | Clinical benefit | 27.8 percentage of participants |
| Phase 1: Isatuximab 20mg/kg Q2W | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | OR | 33.3 percentage of participants |
| Phase 1: Isatuximab 20mg/kg Q2W | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | Clinical benefit | 33.3 percentage of participants |
| Phase 1: Isatuximab 20mg/kg QW | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | Clinical benefit | 28.6 percentage of participants |
| Phase 1: Isatuximab 20mg/kg QW | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | OR | 14.3 percentage of participants |
| Phase 1: Isatuximab 20mg/kg QW | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | OR | 28.6 percentage of participants |
| Phase 1: Isatuximab 20mg/kg QW | Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria | Clinical benefit | 42.9 percentage of participants |
Secondary
Clinical Assessment: Phase 1: Time to First Response (TTR)
TTR was defined as the time from first dose of isatuximab to first response (PR or better). PR: \>=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by \>=90% or \<200mg, \>=50% reduction in size/number of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions.
Time frame: From the date of first dose administration to the date of first response or death (due to any cause) (maximum duration: 120 weeks)
Population: Analysis was performed only on subset of participants who had response in Phase 1 and not for the reporting group with no response.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Clinical Assessment: Phase 1: Time to First Response (TTR) | 0.95 months | — |
| Phase 1: Isatuximab 3mg/kg Q2W | Clinical Assessment: Phase 1: Time to First Response (TTR) | 6.41 months | — |
| Phase 1: Isatuximab 5mg/kg Q2W | Clinical Assessment: Phase 1: Time to First Response (TTR) | 2.52 months | Standard Deviation 3.77 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Clinical Assessment: Phase 1: Time to First Response (TTR) | 1.96 months | Standard Deviation 1.72 |
| Phase 1: Isatuximab 10 mg/kg QW | Clinical Assessment: Phase 1: Time to First Response (TTR) | 1.38 months | Standard Deviation 0.65 |
| Phase 1: Isatuximab 20mg/kg Q2W | Clinical Assessment: Phase 1: Time to First Response (TTR) | 1.18 months | — |
| Phase 1: Isatuximab 20mg/kg QW | Clinical Assessment: Phase 1: Time to First Response (TTR) | 1.46 months | Standard Deviation 0.77 |
Secondary
Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response
ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 1) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment.
Time frame: Up to 120 weeks
Population: Analysis was performed on ADA evaluable population which included all treated participants with at least one ADA assessment with a reportable result during the ADA on-study observation period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment-induced ADA | 2 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment boosted ADA | 0 Participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment-induced ADA | 0 Participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment boosted ADA | 0 Participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment-induced ADA | 0 Participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment boosted ADA | 0 Participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment-induced ADA | 1 Participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment boosted ADA | 0 Participants |
| Phase 1: Isatuximab 10 mg/kg QW | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment-induced ADA | 1 Participants |
| Phase 1: Isatuximab 10 mg/kg QW | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment boosted ADA | 0 Participants |
| Phase 1: Isatuximab 20mg/kg Q2W | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment-induced ADA | 1 Participants |
| Phase 1: Isatuximab 20mg/kg Q2W | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment boosted ADA | 0 Participants |
| Phase 1: Isatuximab 20mg/kg QW | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment boosted ADA | 0 Participants |
| Phase 1: Isatuximab 20mg/kg QW | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment-induced ADA | 1 Participants |
| Phase 1: Isatuximab 20mg/kg QW | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment-induced ADA | 1 Participants |
| Phase 1: Isatuximab 20mg/kg QW | Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | Treatment boosted ADA | 0 Participants |
Secondary
Immunogenicity Assessment: Phase 2 Stage 2: Number of Participants With Anti-drug Antibodies to Isatuximab
ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 2 Stage 2) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment.
Time frame: Up to 97 weeks
Population: Analysis was performed on ADA evaluable population which included all treated participants with at least one ADA assessment with a reportable result during the ADA on-study observation period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Immunogenicity Assessment: Phase 2 Stage 2: Number of Participants With Anti-drug Antibodies to Isatuximab | Treatment induced ADA | 1 Participants |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Immunogenicity Assessment: Phase 2 Stage 2: Number of Participants With Anti-drug Antibodies to Isatuximab | Treatment boosted ADA | 0 Participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Immunogenicity Assessment: Phase 2 Stage 2: Number of Participants With Anti-drug Antibodies to Isatuximab | Treatment induced ADA | 0 Participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Immunogenicity Assessment: Phase 2 Stage 2: Number of Participants With Anti-drug Antibodies to Isatuximab | Treatment boosted ADA | 0 Participants |
Secondary
Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers
Serum/plasma markers included: tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1-β), interleukin 6 (IL-6) and interferon-gamma (IFN-Gamma). Due to change in planned analysis, data for high-sensitivity C-reactive protein (hs-CRP) and CD38 was not collected and analyzed.
Time frame: Cycle 1 Day 1
Population: Analysis was performed on all randomized participants who gave their informed consent, had received at least 1 dose (even incomplete) of isatuximab and had an assessable PD parameter. Here, 'number analyzed' = number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | TNF alpha | 163.181 picogram/milliliter (pg/mL) | Standard Deviation 253.373 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-1 Beta | 64.577 picogram/milliliter (pg/mL) | Standard Deviation 227.399 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-6 | 139.234 picogram/milliliter (pg/mL) | Standard Deviation 212.385 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IFN Gamma | 477.116 picogram/milliliter (pg/mL) | Standard Deviation 1673.063 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IFN Gamma | 5.376 picogram/milliliter (pg/mL) | Standard Deviation 9.312 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-1 Beta | 29.741 picogram/milliliter (pg/mL) | Standard Deviation 55.515 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | TNF alpha | 179.783 picogram/milliliter (pg/mL) | Standard Deviation 191.455 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-6 | 261.732 picogram/milliliter (pg/mL) | Standard Deviation 270.119 |
| Phase 1: Isatuximab 5mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | TNF alpha | 352.974 picogram/milliliter (pg/mL) | Standard Deviation 220.394 |
| Phase 1: Isatuximab 5mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IFN Gamma | 25.806 picogram/milliliter (pg/mL) | Standard Deviation 44.698 |
| Phase 1: Isatuximab 5mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-1 Beta | 7.527 picogram/milliliter (pg/mL) | Standard Deviation 8.118 |
| Phase 1: Isatuximab 5mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-6 | 73.899 picogram/milliliter (pg/mL) | Standard Deviation 53.211 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | TNF alpha | 340.799 picogram/milliliter (pg/mL) | Standard Deviation 341.1 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-1 Beta | 299.058 picogram/milliliter (pg/mL) | Standard Deviation 572.26 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-6 | 148.594 picogram/milliliter (pg/mL) | Standard Deviation 175.719 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IFN Gamma | 445.772 picogram/milliliter (pg/mL) | Standard Deviation 1043.982 |
| Phase 1: Isatuximab 10 mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IFN Gamma | 568.806 picogram/milliliter (pg/mL) | Standard Deviation 1022 |
| Phase 1: Isatuximab 10 mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-6 | 173.004 picogram/milliliter (pg/mL) | Standard Deviation 433.297 |
| Phase 1: Isatuximab 10 mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-1 Beta | 547.770 picogram/milliliter (pg/mL) | Standard Deviation 1454.175 |
| Phase 1: Isatuximab 10 mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | TNF alpha | 503.462 picogram/milliliter (pg/mL) | Standard Deviation 479.813 |
| Phase 1: Isatuximab 20mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IFN Gamma | 627.089 picogram/milliliter (pg/mL) | Standard Deviation 1527.647 |
| Phase 1: Isatuximab 20mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-6 | -8.109 picogram/milliliter (pg/mL) | Standard Deviation 45.845 |
| Phase 1: Isatuximab 20mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-1 Beta | 327.957 picogram/milliliter (pg/mL) | Standard Deviation 759.305 |
| Phase 1: Isatuximab 20mg/kg Q2W | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | TNF alpha | 342.664 picogram/milliliter (pg/mL) | Standard Deviation 410.245 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IFN Gamma | 448.387 picogram/milliliter (pg/mL) | Standard Deviation 569.499 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | TNF alpha | 307.319 picogram/milliliter (pg/mL) | Standard Deviation 398.025 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-6 | 274.616 picogram/milliliter (pg/mL) | Standard Deviation 234.752 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-1 Beta | 305.914 picogram/milliliter (pg/mL) | Standard Deviation 621.754 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-1 Beta | 293.307 picogram/milliliter (pg/mL) | Standard Deviation 612.746 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IL-6 | 165.295 picogram/milliliter (pg/mL) | Standard Deviation 203.451 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | IFN Gamma | 1487.097 picogram/milliliter (pg/mL) | Standard Deviation 2693.826 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers | TNF alpha | 412.541 picogram/milliliter (pg/mL) | Standard Deviation 243.169 |
Secondary
Pharmacokinetic Assessment: Phase 2 Stage 2: Accumulation Ratio of Isatuximab Based on Ctrough
Ctrough is the plasma concentration observed before treatment administration. For 1st category, the accumulation ratio was calculated by dividing Ctrough value of Cycle 2 Day 1 by Cycle 1 Day 8 and for second category, accumulation ratio was calculated by dividing Ctrough value of Cycle 4 Day 1 by Cycle 1 Day 8.
Time frame: Cycle 2, Day 1; Cycle 1, Day 8; Cycle 4, Day 1
Population: Analysis was performed on PK population. Here, 'number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Accumulation Ratio of Isatuximab Based on Ctrough | Cycle 2 Day 1/Cycle 1 Day 8 | 521.38338 ratio | Standard Deviation 4891.6339 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Accumulation Ratio of Isatuximab Based on Ctrough | Cycle 4 Day 1/Cycle 1 Day 8 | 3.58378 ratio | Standard Deviation 2.77398 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Accumulation Ratio of Isatuximab Based on Ctrough | Cycle 2 Day 1/Cycle 1 Day 8 | 3.24370 ratio | Standard Deviation 1.7386 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Accumulation Ratio of Isatuximab Based on Ctrough | Cycle 4 Day 1/Cycle 1 Day 8 | 3.95950 ratio | Standard Deviation 3.1931 |
Secondary
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 1 Week Interval
Time frame: Pre-dose, at the end of infusion, 1 hour and 168 hours post dose on Day 1 of Cycle 1
Population: Analysis was performed on PK population which included participants who gave informed consent, received at least one dose (even if incomplete) of isatuximab, had an assessable PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 1 Week Interval | 37096 mcg*hour/mL | Geometric Coefficient of Variation 80 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 1 Week Interval | 35423 mcg*hour/mL | Geometric Coefficient of Variation 88 |
Secondary
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 2 Weeks Interval
Time frame: Cycle 1, Day 1: pre-dose, at the end of infusion, 168 and 336 hours post-infusion
Population: Analysis was performed on PK population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 2 Weeks Interval | 91271 mcg*hour/mL | Geometric Coefficient of Variation 78 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 2 Weeks Interval | 86761 mcg*hour/mL | Geometric Coefficient of Variation 77 |
Secondary
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 4 Weeks Interval
Time frame: Cycle 1, Day 1: pre-dose, at the end of infusion, 168, 336, and 672 hours post-infusion
Population: Analysis was performed on PK population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 4 Weeks Interval | 236360 mcg*hour/mL | Geometric Coefficient of Variation 72 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 4 Weeks Interval | 226372 mcg*hour/mL | Geometric Coefficient of Variation 66 |
Secondary
Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough)
Time frame: At Days 7, 14 and 28
Population: Analysis was performed on PK population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough) | Day 7 | 137 mcg/mL | Geometric Coefficient of Variation 75 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough) | Day 14 | 230 mcg/mL | Geometric Coefficient of Variation 70 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough) | Day 28 | 360 mcg/mL | Geometric Coefficient of Variation 63 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough) | Day 7 | 128 mcg/mL | Geometric Coefficient of Variation 54 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough) | Day 14 | 214 mcg/mL | Geometric Coefficient of Variation 57 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough) | Day 28 | 305 mcg/mL | Geometric Coefficient of Variation 66 |
Secondary
Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi)
Ceoi was defined as the plasma concentration of Isatuximab at end of infusion. Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). Analysis was performed on PK population: participants who gave informed consent, received at least one dose (even if incomplete) of isatuximab, had an assessable PK parameter.
Time frame: Cycle 1 Day 1 and Cycle 3 Day 1: At the end of infusion
Population: Here, Overall Number of Participants Analyzed=participants evaluable for this outcome measure and 0 in number analyzed field signifies none of the participant were evaluable because at Cycle 3, Day 1, only data for reporting arms Phase 1: Isatuximab 10mg/kg QW and Phase 1: Isatuximab 20mg/kg QW was planned to be collected and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 2.08667 microgram per milliliter (mcg/mL) | Standard Deviation 0.65567 |
| Phase 1: Isatuximab 3mg/kg Q2W | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 13.18333 microgram per milliliter (mcg/mL) | Standard Deviation 5.74464 |
| Phase 1: Isatuximab 5mg/kg Q2W | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 44.22500 microgram per milliliter (mcg/mL) | Standard Deviation 15.30651 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 125.50000 microgram per milliliter (mcg/mL) | Standard Deviation 53.03301 |
| Phase 1: Isatuximab 10 mg/kg QW | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 171.43333 microgram per milliliter (mcg/mL) | Standard Deviation 50.18853 |
| Phase 1: Isatuximab 20mg/kg Q2W | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 148.80000 microgram per milliliter (mcg/mL) | Standard Deviation 18.48513 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 400.33333 microgram per milliliter (mcg/mL) | Standard Deviation 52.51984 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 173.33333 microgram per milliliter (mcg/mL) | Standard Deviation 20.64784 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 3 Day 1 | 299.82500 microgram per milliliter (mcg/mL) | Standard Deviation 220.83898 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 1 Day 1 | 334.33333 microgram per milliliter (mcg/mL) | Standard Deviation 98.28462 |
| Phase 1: Isatuximab 20mg/kg QW | Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi) | Cycle 3 Day 1 | 715.33333 microgram per milliliter (mcg/mL) | Standard Deviation 188.01241 |
Secondary
Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with MM. It has 4 subscales: body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). Disease symptoms subscale used 4-point scale ranged from 1= 'Not at All' to 4= 'Very Much'. Scores were averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL.
Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10 and EOT (anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Population: Analysis was performed on AT population. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure and 'number analyzed' = number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 2 day 1 | 5.56 score on a scale | Standard Deviation 18.36 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 3 day 1 | 7.94 score on a scale | Standard Deviation 11.94 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 4 day 1 | 8.33 score on a scale | Standard Deviation 13.22 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 5 day 1 | -6.94 score on a scale | Standard Deviation 10.52 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 6 day 1 | 8.33 score on a scale | Standard Deviation 7.17 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 7 day 1 | 2.78 score on a scale | Standard Deviation 3.93 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 8 day 1 | -5.56 score on a scale | Standard Deviation 7.86 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 9 day 1 | 5.56 score on a scale | Standard Deviation 7.86 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 10 day 1 | 0.00 score on a scale | Standard Deviation 0 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | End of treatment | -9.72 score on a scale | Standard Deviation 19.44 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 4 day 1 | -3.89 score on a scale | Standard Deviation 16.98 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 10 day 1 | 0.00 score on a scale | Standard Deviation 19.25 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 5 day 1 | 0.51 score on a scale | Standard Deviation 19.95 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 6 day 1 | 1.23 score on a scale | Standard Deviation 23.53 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 7 day 1 | -3.70 score on a scale | Standard Deviation 22.95 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 8 day 1 | -2.78 score on a scale | Standard Deviation 23.5 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | End of treatment | 7.78 score on a scale | Standard Deviation 24.41 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 9 day 1 | -10.00 score on a scale | Standard Deviation 10.69 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 2 day 1 | -3.42 score on a scale | Standard Deviation 11.24 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 3 day 1 | -5.05 score on a scale | Standard Deviation 14.15 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 9 day 1 | -16.67 score on a scale | Standard Deviation 29.75 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 8 day 1 | -15.28 score on a scale | Standard Deviation 23.3 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | End of treatment | 24.07 score on a scale | Standard Deviation 22.45 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 2 day 1 | 0.93 score on a scale | Standard Deviation 13.91 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 5 day 1 | -9.03 score on a scale | Standard Deviation 17.04 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 7 day 1 | -18.06 score on a scale | Standard Deviation 21.93 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 10 day 1 | -15.28 score on a scale | Standard Deviation 30.56 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 3 day 1 | -5.98 score on a scale | Standard Deviation 16.89 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 6 day 1 | -15.08 score on a scale | Standard Deviation 20.96 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 4 day 1 | -10.00 score on a scale | Standard Deviation 16.93 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 6 day 1 | -6.94 score on a scale | Standard Deviation 10.52 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 9 day 1 | -6.94 score on a scale | Standard Deviation 12.32 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 7 day 1 | -11.11 score on a scale | Standard Deviation 11.79 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | End of treatment | 25.00 score on a scale | Standard Deviation 35.36 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 8 day 1 | -4.17 score on a scale | Standard Deviation 5.32 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 3 day 1 | -1.52 score on a scale | Standard Deviation 13.17 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 4 day 1 | 0.62 score on a scale | Standard Deviation 30.1 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 5 day 1 | -6.67 score on a scale | Standard Deviation 17.74 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 2 day 1 | 2.61 score on a scale | Standard Deviation 18.75 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score | Cycle 10 day 1 | -6.67 score on a scale | Standard Deviation 17.3 |
Secondary
Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores
EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.
Time frame: Baseline, Day 1 of Cycles 4, 7, 10, 13, 16, 19, and EOT (anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Population: Analysis was performed on AT population. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure and 'number analyzed' = number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 16 day 1 | 5.00 score on a scale | Standard Deviation 5.66 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | End of treatment | -18.50 score on a scale | Standard Deviation 16.98 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 10 day 1 | 0.50 score on a scale | Standard Deviation 2.12 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 7 day 1 | -2.50 score on a scale | Standard Deviation 0.71 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 4 day 1 | -5.75 score on a scale | Standard Deviation 18.55 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 13 day 1 | 14.00 score on a scale | Standard Deviation 19.8 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | End of treatment | -11.60 score on a scale | Standard Deviation 11.37 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 16 day 1 | 0.67 score on a scale | Standard Deviation 23.71 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 13 day 1 | -5.00 score on a scale | Standard Deviation 4 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 7 day 1 | -6.00 score on a scale | Standard Deviation 27.39 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 4 day 1 | 2.00 score on a scale | Standard Deviation 16.88 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 19 day 1 | -5.50 score on a scale | Standard Deviation 4.95 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 10 day 1 | -10.33 score on a scale | Standard Deviation 9.29 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 10 day 1 | 10.33 score on a scale | Standard Deviation 24.38 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 4 day 1 | -4.78 score on a scale | Standard Deviation 15.71 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 7 day 1 | 9.00 score on a scale | Standard Deviation 18.25 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 13 day 1 | -9.00 score on a scale | — |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | End of treatment | -10.00 score on a scale | Standard Deviation 9.54 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 10 day 1 | -2.60 score on a scale | Standard Deviation 8.11 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 7 day 1 | 1.00 score on a scale | Standard Deviation 7.94 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 4 day 1 | 4.89 score on a scale | Standard Deviation 16.02 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | End of treatment | -9.00 score on a scale | Standard Deviation 0 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores | Cycle 13 day 1 | -5.00 score on a scale | — |
Secondary
Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status
EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & other single items. For each item, high score = high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.
Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10 and End of Treatment (EOT: anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Population: Analysis was performed on AT population. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure and 'number analyzed' = number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 2 day 1 | -8.33 score on a scale | Standard Deviation 20.15 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 3 day 1 | 0.00 score on a scale | Standard Deviation 19.25 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 4 day 1 | 0.00 score on a scale | Standard Deviation 24.53 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 5 day 1 | 0.00 score on a scale | Standard Deviation 24.53 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 6 day 1 | 12.50 score on a scale | Standard Deviation 14.43 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 7 day 1 | 12.50 score on a scale | Standard Deviation 5.89 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 8 day 1 | 0.00 score on a scale | Standard Deviation 35.36 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 9 day 1 | -8.33 score on a scale | Standard Deviation 11.79 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 10 day 1 | -8.33 score on a scale | Standard Deviation 35.36 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | End of treatment | 3.33 score on a scale | Standard Deviation 33.64 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 4 day 1 | -5.30 score on a scale | Standard Deviation 21.5 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 10 day 1 | -16.67 score on a scale | Standard Deviation 22.05 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 5 day 1 | 0.69 score on a scale | Standard Deviation 15.27 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 6 day 1 | -10.19 score on a scale | Standard Deviation 25.27 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 7 day 1 | -3.57 score on a scale | Standard Deviation 15.85 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 8 day 1 | -11.11 score on a scale | Standard Deviation 18.76 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | End of treatment | -11.67 score on a scale | Standard Deviation 13.94 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 9 day 1 | -10.00 score on a scale | Standard Deviation 19.9 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 2 day 1 | 2.22 score on a scale | Standard Deviation 16.51 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 3 day 1 | -0.76 score on a scale | Standard Deviation 16.44 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 9 day 1 | 4.17 score on a scale | Standard Deviation 14.43 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 8 day 1 | 4.17 score on a scale | Standard Deviation 15.96 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | End of treatment | -11.11 score on a scale | Standard Deviation 20.97 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 2 day 1 | -3.95 score on a scale | Standard Deviation 20.67 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 5 day 1 | 6.48 score on a scale | Standard Deviation 21.15 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 7 day 1 | 8.33 score on a scale | Standard Deviation 11.79 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 10 day 1 | 8.33 score on a scale | Standard Deviation 11.79 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 3 day 1 | 6.55 score on a scale | Standard Deviation 19.66 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 6 day 1 | 5.95 score on a scale | Standard Deviation 13.36 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 4 day 1 | 6.06 score on a scale | Standard Deviation 21.11 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 6 day 1 | 10.42 score on a scale | Standard Deviation 7.98 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 9 day 1 | 6.25 score on a scale | Standard Deviation 10.49 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 7 day 1 | 6.67 score on a scale | Standard Deviation 6.97 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | End of treatment | -12.50 score on a scale | Standard Deviation 5.89 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 8 day 1 | 6.25 score on a scale | Standard Deviation 10.49 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 3 day 1 | -2.08 score on a scale | Standard Deviation 15.54 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 4 day 1 | 7.41 score on a scale | Standard Deviation 8.78 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 5 day 1 | 5.00 score on a scale | Standard Deviation 4.56 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 2 day 1 | 0.00 score on a scale | Standard Deviation 15.39 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status | Cycle 10 day 1 | 3.33 score on a scale | Standard Deviation 7.45 |
Secondary
Phase 2 Stage 1: Duration of Response
DOR:Time from date of 1st IAC determined response (\>= PR) that was subsequently confirmed, to date of first IAC determined PD/death, whichever happened earlier. updated IMWG criteria- PR:\>=50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or a \>=50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a \>=50% reduction in size of soft tissue plasmacytomas; PD: Increase of 25% from lowest response value in any of following: Serum M-protein \>=0.5 g/dL absolute increase and/or urine M-protein \>=200 mg/24 hours absolute increase and/or \>10 mg/dL absolute increase in difference between involved and uninvolved FLC levels, \>=10% bone marrow plasma cells (PCs), development of new bone lesions/soft tissue plasmacytomas or definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium \>11·5 mg/dl) attributed to PC proliferation disorder.
Time frame: From the date of first response until disease progression or death or data cut-off (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Population: Analysis was performed only on subset of population who had response in Phase 2 stage 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Duration of Response | 1.91 months | — |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Duration of Response | 11.17 months | Standard Deviation 5.77 |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Duration of Response | 7.31 months | Standard Deviation 3.65 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Duration of Response | 8.11 months | Standard Deviation 2.33 |
Secondary
Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Time frame: From Baseline up to 30 days after the last dose (maximum duration: 414 weeks for Stage 1a and 92 weeks for Stage 1b)
Population: Analysis was performed on AT population which included Participants who signed informed consent \& received at least 1 dose/even incomplete of isatuximab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 22 Participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 24 Participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 25 Participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 25 Participants |
Secondary
Phase 2 Stage 1: Overall Survival (OS)
OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method.
Time frame: From the date of randomization to date of death from any cause (maximum duration 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Population: Analysis was performed on AT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Overall Survival (OS) | 15.277 months |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Overall Survival (OS) | 18.628 months |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Overall Survival (OS) | NA months |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Overall Survival (OS) | NA months |
Secondary
Phase 2 Stage 1: Percentage of Participants With Clinical Benefit
Clinical benefit: participants with sCR, CR, VGPR, PR or MR as per IMWG criteria, determined by IAC. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytomas,\<5% PCs in bone marrow aspirates. sCR: CR + normal FLC ratio (0.26-1.65), absence of clonal cells in bone marrow biopsy. VGPR: serum & urine M-component detectable by immunofixation, not on electrophoresis/,\>=90% reduction in serum M-component plus urine M-component level \<100mg/24hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours, ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline, ≥50% size reduction in soft tissue plasmacytomas. MR:\>=25 but \<49% reduction in serum M-protein, reduction in 24h urine M-protein by 50-89%, 25-49% size reduction in soft tissue plasmacytomas.
Time frame: From the date of randomization to the date of first documentation of progression or death (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Population: Analysis was performed on AT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Percentage of Participants With Clinical Benefit | 4.3 percentage of participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Percentage of Participants With Clinical Benefit | 41.7 percentage of participants |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Percentage of Participants With Clinical Benefit | 32.0 percentage of participants |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Percentage of Participants With Clinical Benefit | 36.0 percentage of participants |
Secondary
Phase 2 Stage 1: Progression Free Survival (PFS)
PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression (PD) or date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of \> 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be \> 0.5 g/dL), Urine M-component and/or (the absolute increase must be \> 200 mg/24 h), \> 10mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, \>10% absolute percentage of bone marrow plasma cell, definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method.
Time frame: From the date of the first dose administration until progression or death, whichever occurred first (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Population: Analysis was performed on AT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 1: Progression Free Survival (PFS) | 2.1 months |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 1: Progression Free Survival (PFS) | 9.6 months |
| Phase 1: Isatuximab 5mg/kg Q2W | Phase 2 Stage 1: Progression Free Survival (PFS) | 4.4 months |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | Phase 2 Stage 1: Progression Free Survival (PFS) | 3.6 months |
Secondary
Phase 2 Stage 2: Duration of Response
DOR: Time from date of 1st IAC determined response (\>= PR) that was subsequently confirmed, to date of 1st IAC determined PD or death, whichever happened earlier. As per updated IMWG criteria-PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. ≥50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline ≥50% reduction in size of soft tissue plasmacytomas; PD: Increase of \>25% from lowest response value in any one of following: Serum M-component (absolute increase must be \>0.5 g/dL)4 and/or Urine M-component (absolute increase must be \>200 mg/24 h) and/or \>10 mg/dL absolute increase in difference between involved and uninvolved FLC levels, \>=10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) attributed solely to plasma cell proliferative disorder.
Time frame: From the date of first response until disease progression or death or data cut-off (maximum duration: 97 weeks)
Population: Analysis was performed only on subset of population who had response in Phase 2 stage 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 2: Duration of Response | 8.6 months | Standard Deviation 5.2 |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 2: Duration of Response | 10.9 months | Standard Deviation 4.6 |
Secondary
Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Time frame: From Baseline up to 30 days after the last dose (maximum duration: 301 weeks)
Population: Analysis was performed on AT population which included participants who signed informed consent \& received at least 1 dose/even incomplete of isatuximab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 101 Participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 51 Participants |
Secondary
Phase 2 Stage 2: Overall Survival
OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method.
Time frame: From the date of randomization to date of death from any cause (maximum duration: 97 weeks)
Population: Analysis was performed on AT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 2: Overall Survival | 18.92 months |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 2: Overall Survival | 17.25 months |
Secondary
Phase 2 Stage 2: Percentage of Participants With Clinical Benefit
Clinical benefit:participants with sCR, CR, VGPR, PR or MR, per IMWG criteria, determined by IAC. CR:negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytomas,\<5% plasma cells in bone marrow aspirates,normal FLC ratio(0.26-1.65) in participants with only FLC disease.sCR:CR+normal FLC ratio, absence of clonal cells in bone marrow biopsy.VGPR:serum & urine M-component detectable by immunofixation, not on electrophoresis/,\>=90% reduction in serum M-component plus urine M-component level \<100mg/24h/,\>=90% decrease in difference between involved and uninvolved FLC levels; PR:\>=50% reduction of serum M-protein, reduction in 24h urinary M-protein by \>=90%/\<200mg/24h,\>50% decrease in difference between involved and uninvolved FLC in place of M-protein criteria, \>=50% reduction in size/number of soft tissue plasmacytomas. MR:\>=25 but \<49% reduction in serum M-protein,reduction in 24h urine M-protein by 50-89%, 25-49% reduction in size of soft tissue plasmacytomas
Time frame: From the date of randomization to the date of first documentation of progression or death (maximum duration: 97 weeks )
Population: Analysis was performed on AT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 2: Percentage of Participants With Clinical Benefit | 43.1 percentage of participants |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 2: Percentage of Participants With Clinical Benefit | 54.5 percentage of participants |
Secondary
Phase 2 Stage 2: Progression Free Survival
PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression or the date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of \>25% from lowest response value in any one of the following: Serum M-component (the absolute increase must be \>0.5 g/dL)4 and/or Urine M-component (the absolute increase must be \>200 mg/24 h) and/or \>10 mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, ≥10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method.
Time frame: From the date of the first dose administration until progression or death, whichever occurred first (maximum duration: 97 weeks)
Population: Analysis was performed on AT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | Phase 2 Stage 2: Progression Free Survival | 4.86 months |
| Phase 1: Isatuximab 3mg/kg Q2W | Phase 2 Stage 2: Progression Free Survival | 10.15 months |
Secondary
PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab
Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). Analysis was performed on PK population.
Time frame: For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion
Population: Here, Overall Number of Participants Analyzed=participants evaluable for this outcome measure and 0 in number analyzed field signifies none of the participant were evaluable because at Cycle 3, Day 1, only data for reporting arms Phase 1: Isatuximab 10mg/kg QW and Phase 1: Isatuximab 20mg/kg QW was planned to be collected and analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 2.00 mcg/mL | Geometric Coefficient of Variation 31 |
| Phase 1: Isatuximab 3mg/kg Q2W | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 12.4 mcg/mL | Geometric Coefficient of Variation 45 |
| Phase 1: Isatuximab 5mg/kg Q2W | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 53.7 mcg/mL | Geometric Coefficient of Variation 28 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 126 mcg/mL | — |
| Phase 1: Isatuximab 10 mg/kg QW | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 181 mcg/mL | Geometric Coefficient of Variation 48 |
| Phase 1: Isatuximab 20mg/kg Q2W | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 154 mcg/mL | Geometric Coefficient of Variation 13 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 457 mcg/mL | Geometric Coefficient of Variation 28 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 181 mcg/mL | Geometric Coefficient of Variation 20 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 3 Day 1 | 265 mcg/mL | Geometric Coefficient of Variation 67 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 1 Day 1 | 343 mcg/mL | Geometric Coefficient of Variation 29 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab | Cycle 3 Day 1 | 712 mcg/mL | Geometric Coefficient of Variation 27 |
Secondary
PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow).
Time frame: Week 1, 2 and 3
Population: Analysis was performed on PK population. Here, 'number analyzed' = number of participants with available data for each category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1 | 0.00223 mcg/mL | Geometric Coefficient of Variation 86 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 3 | 0.000283 mcg/mL | Geometric Coefficient of Variation 145 |
| Phase 1:Isatuximab <=1 mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 2 | 0.000800 mcg/mL | Geometric Coefficient of Variation 173 |
| Phase 1: Isatuximab 3mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 3 | 0.460 mcg/mL | Geometric Coefficient of Variation 121 |
| Phase 1: Isatuximab 3mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 2 | 0.181 mcg/mL | Geometric Coefficient of Variation 136 |
| Phase 1: Isatuximab 3mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1 | 1.44 mcg/mL | Geometric Coefficient of Variation 85 |
| Phase 1: Isatuximab 5mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 3 | 42.7 mcg/mL | Geometric Coefficient of Variation 73 |
| Phase 1: Isatuximab 5mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1 | 15.3 mcg/mL | Geometric Coefficient of Variation 90 |
| Phase 1: Isatuximab 5mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 2 | 1.39 mcg/mL | Geometric Coefficient of Variation 116 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1 | 27.6 mcg/mL | Geometric Coefficient of Variation 81 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 2 | 1.97 mcg/mL | Geometric Coefficient of Variation 145 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 3 | 4.18 mcg/mL | Geometric Coefficient of Variation 133 |
| Phase 1: Isatuximab 10 mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 2 | 8.31 mcg/mL | Geometric Coefficient of Variation 77 |
| Phase 1: Isatuximab 10 mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1 | 44.2 mcg/mL | Geometric Coefficient of Variation 52 |
| Phase 1: Isatuximab 10 mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 3 | 18.6 mcg/mL | Geometric Coefficient of Variation 71 |
| Phase 1: Isatuximab 20mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 2 | 55.1 mcg/mL | Geometric Coefficient of Variation 63 |
| Phase 1: Isatuximab 20mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1 | 20.7 mcg/mL | Geometric Coefficient of Variation 63 |
| Phase 1: Isatuximab 20mg/kg Q2W | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 3 | 75.9 mcg/mL | Geometric Coefficient of Variation 78 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 2 | 63.9 mcg/mL | Geometric Coefficient of Variation 46 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1 | 113 mcg/mL | Geometric Coefficient of Variation 37 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 3 | 91.0 mcg/mL | Geometric Coefficient of Variation 52 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 1 | 108 mcg/mL | Geometric Coefficient of Variation 33 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 2 | 194.8 mcg/mL | Geometric Coefficient of Variation 36 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 | Week 3 | 347.3 mcg/mL | Geometric Coefficient of Variation 36 |
Secondary
PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W)
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow).
Time frame: For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 336 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 336 hr post-infusion
Population: Analysis was performed on PK population. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | 222 mcg*hour/mL | Geometric Coefficient of Variation 80 |
| Phase 1: Isatuximab 3mg/kg Q2W | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | 3076 mcg*hour/mL | Geometric Coefficient of Variation 35 |
| Phase 1: Isatuximab 5mg/kg Q2W | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | 9546 mcg*hour/mL | Geometric Coefficient of Variation 70 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | 14876 mcg*hour/mL | Geometric Coefficient of Variation 64 |
| Phase 1: Isatuximab 10 mg/kg QW | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | 18967 mcg*hour/mL | Geometric Coefficient of Variation 44 |
| Phase 1: Isatuximab 20mg/kg Q2W | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | 30187 mcg*hour/mL | Geometric Coefficient of Variation 40 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | 48003 mcg*hour/mL | Geometric Coefficient of Variation 31 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W) | 71174 mcg*hour/mL | Geometric Coefficient of Variation 29 |
Secondary
PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W)
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow).
Time frame: For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion
Population: Analysis was performed on PK population. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | 222 mcg*hour/mL | Geometric Coefficient of Variation 80 |
| Phase 1: Isatuximab 3mg/kg Q2W | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | 2624 mcg*hour/mL | Geometric Coefficient of Variation 24 |
| Phase 1: Isatuximab 5mg/kg Q2W | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | 7174 mcg*hour/mL | Geometric Coefficient of Variation 54 |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | 11566 mcg*hour/mL | Geometric Coefficient of Variation 48 |
| Phase 1: Isatuximab 10 mg/kg QW | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | 13480 mcg*hour/mL | Geometric Coefficient of Variation 38 |
| Phase 1: Isatuximab 20mg/kg Q2W | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | 12680 mcg*hour/mL | Geometric Coefficient of Variation 35 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | 32739 mcg*hour/mL | Geometric Coefficient of Variation 28 |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W) | 28405 mcg*hour/mL | Geometric Coefficient of Variation 27 |
Secondary
PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab
Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab \<=1mg/kg in participant flow). Analysis was performed on PK population.
Time frame: For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion
Population: Here, Overall Number of Participants Analyzed=participants evaluable for this outcome measure and 0 in number analyzed field signifies none of the participant were evaluable because at Cycle 3, Day 1, only data for reporting arms Phase 1: Isatuximab 10mg/kg QW and Phase 1: Isatuximab 20mg/kg QW was planned to be collected and analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1:Isatuximab <=1 mg/kg Q2W | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 2.49 hours |
| Phase 1: Isatuximab 3mg/kg Q2W | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 4.35 hours |
| Phase 1: Isatuximab 5mg/kg Q2W | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 6.99 hours |
| Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma) | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 7.65 hours |
| Phase 1: Isatuximab 10 mg/kg QW | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 4.28 hours |
| Phase 1: Isatuximab 20mg/kg Q2W | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 4.92 hours |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 5.87 hours |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 2.25 hours |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 3 Day 1 | 4.30 hours |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 1 Day 1 | 6.83 hours |
| Phase 1: Isatuximab 20mg/kg QW | PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab | Cycle 3 Day 1 | 8.07 hours |