Trial Outcomes & Findings for Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients (NCT NCT02812706)

Last Updated: 2024-04-01

Results Overview

DLTs: AEs occurring during 1st treatment cycle, assessed per national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 4.03. DLTs included: Hematologic DLTs: Grade(G) 4 neutropenia(N) lasting greater than or equal to (\>=) 5 days; G3 to G4 N with fever or microbiologically or radiographically documented infection; G4 thrombocytopenia lasting for \>=5 days; thrombocytopenia, treatment delay greater than (\>)14 days due to hematologic toxicity. Non-hematologic DLTs: G\>=3 non-hematological AE, excluding G3 fatigue, G 3 to 4 electrolyte abnormalities, G3 nausea/vomiting/diarrhea if responsive to optimal medical management within 48 hours or allergic reaction/ hypersensitivity attributed to isatuximab; AE that required treatment delay for \>14 days. Any other toxicity deemed by Investigator or sponsor to be dose-limiting, regardless of the grade, was also considered DLT.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Cycle 1 (28 days)

Results posted on

2024-04-01

Participant Flow

The study was conducted at 13 centers in Japan. A total of 36 participants were enrolled between 05 September 2016 and 6 April 2018, and received isatuximab monotherapy.

Study consisted of 2 phases: Phase 1 and Phase 2. Phase I (Cohorts 1 and 2) was a dose escalation part to evaluate the safety, pharmacokinetics (PK), and efficacy of isatuximab. Phase 2 was commenced after completion of the DLT observation period in Phase 1 and determination of the recommended dose to be used in Phase 2.

Participant milestones

Participant milestones
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg Participants received Isatuximab 10 milligram per kilogram (mg/kg) intravenous (IV) infusion once every week (QW) for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then every 2 weeks (Q2W) (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable adverse events (AEs), disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).	Phase 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 248 weeks).
Phase 1 STARTED	3	5	0
Phase 1 COMPLETED	0	0	0
Phase 1 NOT COMPLETED	3	5	0
Phase 2 STARTED	0	0	28
Phase 2 COMPLETED	0	0	0
Phase 2 NOT COMPLETED	0	0	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg Participants received Isatuximab 10 milligram per kilogram (mg/kg) intravenous (IV) infusion once every week (QW) for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then every 2 weeks (Q2W) (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable adverse events (AEs), disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).	Phase 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 248 weeks).
Phase 1 Adverse Event	0	2	0
Phase 1 Progressive disease	3	3	0
Phase 2 Adverse Event	0	0	2
Phase 2 Progressive disease	0	0	22
Phase 2 Other-Unspecified	0	0	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=5 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).	Phase 2: Isatuximab 20 mg/kg n=28 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 248 weeks).	Total n=36 Participants Total of all reporting groups
Age, Continuous	67.3 years STANDARD_DEVIATION 7.6 • n=99 Participants	74.4 years STANDARD_DEVIATION 4.7 • n=107 Participants	70.6 years STANDARD_DEVIATION 8.1 • n=206 Participants	70.9 years STANDARD_DEVIATION 7.7 • n=7 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	4 Participants n=107 Participants	10 Participants n=206 Participants	16 Participants n=7 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	1 Participants n=107 Participants	18 Participants n=206 Participants	20 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	3 Participants n=99 Participants	5 Participants n=107 Participants	28 Participants n=206 Participants	36 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 days)

Population: Analysis was performed on DLT evaluable population that included subset of participants who completed the first Cycle which consisted of 4 isatuximab administrations of the study drug or they discontinued study drug before completion of first cycle for a DLT. .

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=4 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From the date of the first response until the primary analysis data cut-off date of 31 July 2018 (median duration of follow-up was 24.14 weeks)

Population: Analysis was performed on all treated population.

Percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) assessed by International Myeloma Working Group (IMWG) uniform response criteria. sCR: CR as defined plus normal FLC ratio \& absence of clonal cells in bone marrow. CR: negative immunofixation on serum \& urine; disappearance of any soft tissue plasmacytomas; \<5% plasma cells in bone marrow; normal FLC ratio of 0.26-1.65. VGPR: serum \& urine M-protein detectable by immunofixation; \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 h; \>90% decrease in difference between involved \& uninvolved FLC levels required. PR: \>=50% reduction of serum M-protein \& reduction in 24h urinary M protein by \>=90%/\<200 mg/24 h; if serum \& urine M-protein unmeasurable:\>=50% decrease in difference between involved \& uninvolved FLC; if serum \& urine M-protein not measurable:\>=50% reduction in plasma cells required, in place of M-protein.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Percentage of Participants With Overall Response (OR)	32.1 percentage of participants	—

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days after the last dose of study drug administration (maximum duration of exposure: up to 112 weeks for Cohort 1 and 137 weeks for Cohort 2)

Population: Analysis was performed on all treated population.

An AE was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TESAEs was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that develop, worsened or became serious during the on-treatment period (time from first dose of study drug up to 30 days after the last dose of study drug administration).

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=5 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TEAEs	3 Participants	4 Participants
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TESAEs	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days after the last dose of study drug administration (maximum duration of exposure: up to 248 weeks)

Population: Analysis was performed on all treated population.

An AE was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. TESAEs was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs are defined as AEs that develop, worsened or became serious during the on-treatment period (time from first dose of study drug up to 30 days after the last dose of study drug administration).

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TEAEs	25 Participants	—
Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TESAEs	11 Participants	—

SECONDARY outcome

Timeframe: From the date of the first response until disease progression, or death due to any cause, whichever comes first (maximum duration of exposure: up to 112 weeks for Cohort 1 and 137 weeks for Cohort 2)

Population: Analysis was performed on all treated population.

Percentage of participants with sCR, CR, VGPR, and PR assessed by IMWG uniform response criteria. sCR: CR as defined plus normal FLC ratio \& absence of clonal cells in bone marrow. CR: negative immunofixation on serum \& urine; disappearance of any soft tissue plasmacytomas; \<5 percentage (%) plasma cells in bone marrow; normal FLC ratio of 0.26-1.65. VGPR: serum \& urine M-protein detectable by immunofixation; \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hour (h); \>90% decrease in difference between involved \& uninvolved FLC levels required. PR: \>=50% reduction of serum M-protein \& reduction in 24h urinary M protein by \>=90%/\<200 mg/24 h; if serum \& urine M-protein unmeasurable:\>=50% decrease in difference between involved \& uninvolved FLC; if serum \& urine M-protein not measurable:\>=50% reduction in plasma cells required, in place of M-protein.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=5 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Percentage of Participants With Overall Response (OR)	66.7 percentage of participants	60.0 percentage of participants

SECONDARY outcome

Population: Analysis was performed on a subset of participants who had response.

DOR: time (in weeks) from date of first response to date of subsequent progressive disease (PD) or death, whichever happens earlier. In absence of confirmation of subsequent PD or death before cut-off date, DOR was censored at date of last valid assessment performed or date of initiation of new anticancer treatment, whichever was earlier. PD (IMWG criteria): increase (inc.) of \>=25% from lowest response value in any one of following: serum M-component (absolute inc.\>=0.5 g/dL) and/or; urine M-component (absolute inc.\>=200 mg/24h) and/or, in participants without measurable serum \& urine M-protein: difference between involved \& uninvolved FLC levels (absolute inc. \>10 mg/dL); in participants without measurable serum \& urine M-protein and without measurable disease by FLC levels, bone marrow plasma cell % (absolute % \>=10%); development of new bone lesions or soft tissue plasmacytomas/definite inc. in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=2 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=3 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Duration of Response (DOR)	100.64 weeks Standard Deviation 7.78	113.90 weeks Standard Deviation 18.45

SECONDARY outcome

Timeframe: From date of first study treatment administration until first documented response, or death due to any cause, whichever comes first (maximum duration of exposure: up to 248 weeks)

Population: Analysis was performed on all treated population. Data for this outcome measure was not planned to be collected and analyzed for Phase 1.

CB defined as percentage of participants with sCR, CR, VGPR, PR or Minor/minimal response (MR) assessed by IMWG criteria. sCR: CR as defined plus normal FLC ratio \& absence of clonal cells. CR: negative immunofixation on serum \& urine; disappearance of any soft tissue plasmacytomas; \<5% plasma cells in bone marrow; normal FLC ratio: 0.26-1.65. VGPR: serum \& urine M-protein detectable by immunofixation; \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24h; \>90% decrease in difference between involved \& uninvolved FLC levels required. PR: \>=50% reduction of serum M-protein \& reduction in 24h urinary M protein by \>=90%/\<200 mg/24 h; if serum \& urine M-protein unmeasurable:\>=50% decrease in difference between involved \& uninvolved FLC; if serum \& urine M-protein not measurable:\>=50% reduction in plasma cells required. MR: \>=25% but \<=49% reduction of serum M protein and reduction in 24h urine M protein by 50-89%; 25-49% reduction in size of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Percentage of Participants With Clinical Benefit (CB)	53.6 percentage of participants	—

SECONDARY outcome

Timeframe: From date of first study treatment administration to the date of death due to any cause (maximum duration of exposure: up to 248 weeks)

Population: Analysis was performed on all treated population. Data for this outcome measure was not planned to be collected and analyzed for Phase 1.

Overall survival was defined as the time interval (in months) from the date of first study treatment administration to death due to any cause. In the absence of the confirmation of death before the cut-off date, OS was censored at the last date the participant was known to be alive or at the study cut-off date, whichever was earlier. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Overall Survival (OS)	NA months Interval 20.24 to Median and upper limit of 95% confidence interval (CI) was not estimable due to the smaller number of participants with events.	—

SECONDARY outcome

Timeframe: From date of first study treatment administration until disease progression or death due to any cause, whichever comes first (maximum duration of exposure: up to 248 weeks)

Population: Analysis was performed on all treated population. Analysis was performed by Kaplan-Meier method. Data for this outcome measure was not planned to be collected and analyzed for Phase 1.

PFS was defined as the time interval (in months) from date of first study treatment administration until disease progression or death due to any cause, whichever comes first. In absence of PD or death, PFS was censored at date of last valid assessment performed before cut-off date or date of initiation of new anticancer treatment, whichever was earlier. PD (IMWG criteria): inc. of \>=25% in any one of following: serum M-component absolute (abs.) inc. \>=0.5 g/dL) and/or; urine M-component (abs. inc. \>=200 mg/24h) and/or, in participants without measurable serum \& urine M-protein, difference between involved \& uninvolved FLC levels (abs. inc. \>10 mg/dL); in participants without measurable serum \& urine M-protein \& without measurable disease by FLC levels: bone marrow plasma cell % (abs. % \>=10%); definite development of new bone lesions or soft tissue plasmacytomas or definite inc. in size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Progression Free Survival (PFS)	5.6 months Interval 3.75 to 12.98	—

SECONDARY outcome

Timeframe: From the date of first response until disease progression, or death due to any cause, whichever comes first (maximum duration of exposure: up to 248 weeks)

Population: Analysis was performed on a subset of participants who had response.

DOR was defined as time (in weeks) from date of first response to date of subsequent progressive disease (PD) or death, whichever happens earlier. In absence of confirmation of subsequent PD or death before cut-off date, DOR was censored at date of last valid assessment performed or date of initiation of new anticancer treatment, whichever was earlier. PD (IMWG criteria):inc. of \>=25% from lowest response value in any one of following: serum M-component (absolute inc.\>=0.5 g/dL) and/or; urine M-component (absolute inc.\>=200 mg/24h) and/or, in participants without measurable serum \& urine M-protein: difference between involved \& uninvolved FLC levels (absolute inc.\>10 mg/dL); in participants without measurable serum \& urine M-protein and without measurable disease by FLC levels, bone marrow plasma cell % (absolute% \>=10%); development of new bone lesions or soft tissue plasmacytomas/definite inc. in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=9 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Duration of Response (DOR)	58.70 weeks Standard Deviation 29.91	—

SECONDARY outcome

Timeframe: From date of first study treatment administration until disease progression, or death due to any cause, whichever comes first (maximum duration of exposure: up to 248 weeks)

Population: Analysis was performed on all treated population. Analysis was performed by Kaplan-Meier method. Data for this outcome measure was not planned to be collected and analyzed for Phase 1.

TTP: time interval (in months) from date of first study treatment administration to date of first assessed disease progression. In absence of disease progression, TTP was censored at date of last valid assessment performed before cut-off date or date of initiation of new anticancer treatment, whichever was earlier. PD (IMWG criteria): inc. of \>=25% from lowest response value in any one of following: serum M-component (absolute inc.\>=0.5 g/dL) and/or; urine M-component (absolute inc.\>=200 mg/24h) and/or, in participants without measurable serum \& urine M-protein: difference between involved \& uninvolved FLC levels (absolute inc.\>10 mg/dL); in participants without measurable serum \& urine M-protein and without measurable disease by FLC levels, bone marrow plasma cell % (absolute% \>=10%); development of new bone lesions or soft tissue plasmacytomas/definite inc. in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Time to Progression (TTP)	5.5 months Interval 3.745 to 12.977	—

SECONDARY outcome

Timeframe: End of infusion on Day 1 of Cycle 1

Population: Analysis was performed on PK population that included all participants who gave their informed consent and received at least one dose (even incomplete) of Isatuximab; with data for at least 1 PK parameter available. Here, "Overall number of participants analyzed" = participants with available data for this outcome measure.

Ceoi is the plasma concentration observed at the end of intravenous infusion.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=4 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Plasma Concentration Observed at the End of Intravenous Infusion (Ceoi) of Isatuximab	122 micrograms per milliliter Standard Deviation 21.6	246 micrograms per milliliter Standard Deviation 51.8

SECONDARY outcome

Timeframe: Cycle 1 Day 1 at 0 hour (pre-dose), mid-infusion (2 hours post-infusion), end of infusion (EOI) and EOI+4-hour, Day 2 (24 hour), Day 3 (48 hour), Day 4 (72 hour) and pre-dose on Day 8 (0 hour)

Population: Analysis was performed on PK population. Here, "Overall number of participants analyzed" = participants with available data for this outcome measure.

Cmax was defined as the maximum concentration observed after the first infusion calculated using the non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=4 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Maximum Observed Concentration (Cmax) After First Infusion of Isatuximab	124 micrograms per milliliter Standard Deviation 22.9	280 micrograms per milliliter Standard Deviation 64.4

SECONDARY outcome

Timeframe: Cycle 1 Day 1 at 0 hour (pre-dose), mid-infusion (2 hours post-infusion), EOI and EOI+4-hour, Day 2 (24 hour), Day 3 (48 hour), Day 4 (72 hour) and pre-dose on Day 8 (0 hour)

Population: Analysis was performed on PK population. Here, "Overall number of participants analyzed" = participants with available data for this outcome measure.

Tmax was defined as the time to reach Cmax, calculated using the non-compartmental analysis after the intravenous infusion.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=4 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Time to Reach the Maximum Concentration (Tmax) After First Infusion of Isatuximab	2.68 hours Interval 2.32 to 7.25	5.56 hours Interval 3.28 to 8.48

SECONDARY outcome

Timeframe: Cycle 1 Day 1 at 0 hour (pre-dose), mid-infusion (2 hours post-infusion), EOI and EOI+4-hour, Day 2 (24 hour), Day 3 (48 hour), Day 4 (72 hour) and pre-dose on Day 8 (0 hour)

Population: Analysis was performed on PK population. Here, "Overall number of participants analyzed" = participants with available data for this outcome measure.

AUC was defined as area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=4 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Area Under the Plasma Concentration Versus Curve Over the Dosing Interval (AUC1-week) After First Infusion of Isatuximab	9300 micrograms*hours per milliliter Standard Deviation 3010	21300 micrograms*hours per milliliter Standard Deviation 5520

SECONDARY outcome

Timeframe: Pre-infusion on Cycle 1 Day 8 (C1 D8), C1 D15, C1 D22, C2 D1, C2 D15, C3 D1, C3 D15, C4 D1, C4 D15, C5 D1, C5 D15, C6 D1, C6 D15, C7 D1, C7 D15, C8 D1, C8 D15, C9 D1, C9 D15, C10 D1, C10 D15, C11 D1

Population: Analysis was performed on PK population. Here, "Number analyzed" = participants with available data for each specified category and "0" in the number analyzed field signifies that no participants were available for analysis at specified timepoint.

Ctrough was the plasma concentration observed just before treatment administration during repeated dosing.

Outcome measures

SECONDARY outcome

Timeframe: Multiple timepoints from Cycle 1 to Cycle 10

Population: Analysis was performed on PK population. Here, "Overall number of participants analyzed" = participants with available data for this outcome measure.

Cmax was predicted using population pharmacokinetic model.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Maximum Observed Concentration (Cmax) After First Infusion of Isatuximab	747.83 micrograms per milliliter Standard Deviation 743.83	—

SECONDARY outcome

Timeframe: Multiple timepoints from Cycle 1 to Cycle 10

Population: Analysis was performed on PK population. Here, "Overall number of participants analyzed" = participants with available data for this outcome measure.

AUC was predicted using population pharmacokinetic model.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Area Under the Plasma Concentration Versus Curve Over the Dosing Interval (AUC1-Week) After First Infusion of Isatuximab	65071 micrograms * hours per milliliter Standard Deviation 55554	—

SECONDARY outcome

Timeframe: Pre-infusion on C1 D8, C1 D15, C1 D22, C2 D1, C2 D15, C3 D1, C3 D15, C4 D1, C4 D15, C5 D1, C5 D15, C6 D1, C6 D15, C7 D1, C7 D15, C8 D1, C8 D15, C9 D1, C9 D15, C10 D1, C10 D15

Population: Analysis was performed on PK population. Here, "Number analyzed" = participants with available data for each specified category.

Ctrough was the plasma concentration observed just before treatment administration during repeated dosing.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 1 Day 8	376.34 micrograms per milliliter Standard Deviation 666.40	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 1 Day 15	662.52 micrograms per milliliter Standard Deviation 1283.39	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 1 Day 22	604.17 micrograms per milliliter Standard Deviation 996.78	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 2 Day 1	927.63 micrograms per milliliter Standard Deviation 1194.16	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 2 Day 15	826.15 micrograms per milliliter Standard Deviation 958.75	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 3 Day 1	734.39 micrograms per milliliter Standard Deviation 675.85	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 3 Day 15	689.85 micrograms per milliliter Standard Deviation 715.21	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 4 Day 1	723.76 micrograms per milliliter Standard Deviation 802.83	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 4 Day 15	619.35 micrograms per milliliter Standard Deviation 356.21	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 5 Day 1	647.24 micrograms per milliliter Standard Deviation 338.97	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 5 Day 15	683.90 micrograms per milliliter Standard Deviation 391.48	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 6 Day 1	674.20 micrograms per milliliter Standard Deviation 439.78	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 6 Day 15	742.93 micrograms per milliliter Standard Deviation 420.34	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 7 Day 1	733.83 micrograms per milliliter Standard Deviation 373.26	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 7 Day 15	786.27 micrograms per milliliter Standard Deviation 331.38	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 8 Day 1	870.09 micrograms per milliliter Standard Deviation 443.79	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 8 Day 15	1004.00 micrograms per milliliter Standard Deviation 463.82	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 9 Day 1	946.25 micrograms per milliliter Standard Deviation 369.91	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 9 Day 15	878.63 micrograms per milliliter Standard Deviation 313.39	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 10 Day 1	823.75 micrograms per milliliter Standard Deviation 314.95	—
Phase 2: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 10 Day 15	845.38 micrograms per milliliter Standard Deviation 322.48	—

SECONDARY outcome

Timeframe: At Baseline (Day 1)

Population: Participants treated with Isatuximab (Phase 1 and 2) and evaluable for CD38 receptor density assessment. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

CD38 receptor density assessed from bone marrow aspirates for responder and non-responders' participants was reported.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=18 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=14 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1 and 2: CD38 Receptor Density at Baseline	113226.2 sMEC Standard Deviation 93628.7	133378.2 sMEC Standard Deviation 55518.5

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days after last study drug administration (maximum duration of exposure: up to 112 weeks for Cohort 1, and 137 weeks for Cohort 2)

Population: Analysis was performed on ADA population which included all participants that received isatuximab in Phase 1 part of the study, with at least one ADA assessment reportable during the ADA on-study observation periods.

ADA were categorized as: treatment induced, and treatment boosted response. Treatment-induced ADA: ADA that developed at any time during the ADA on-study observation period in participants without preexisting ADA (ADA that was present in samples drawn during the ADA pretreatment period). Treatment boosted ADA: Preexisting ADA with an increase in titer value between pretreatment \& posttreatment samples of at least two titer steps, during the ADA on-study observation period.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=5 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab Treatment-induced ADA	0 Participants	0 Participants
Phase 1: Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab Treatment boosted ADA	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days after last study drug administration (maximum duration of exposure: up to 248 weeks)

Population: Analysis was performed on ADA population which included all participants that received isatuximab in Phase 2 part of the study, with at least one ADA assessment reportable during the ADA on-study observation periods.

Outcome measures

Outcome measures
Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=28 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 2: Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab Treatment-induced ADA	6 Participants	—
Phase 2: Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab Treatment boosted ADA	0 Participants	—

Adverse Events

Phase 1, Cohort 1: Isatuximab 10 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Phase 1, Cohort 2: Isatuximab 20 mg/kg

Serious events: 2 serious events

Other events: 4 other events

Deaths: 2 deaths

Phase 2: Isatuximab 20 mg/kg

Serious events: 11 serious events

Other events: 24 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Phase 1, Cohort 1: Isatuximab 10 mg/kg n=3 Participants Participants received Isatuximab 10 mg/kg IV infusion QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).	Phase 1, Cohort 2: Isatuximab 20 mg/kg n=5 Participants Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 1 Day 8	23.77 micrograms per milliliter Standard Deviation 8.98	78.52 micrograms per milliliter Standard Deviation 38.49
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 1 Day 15	71.33 micrograms per milliliter Standard Deviation 22.87	186.33 micrograms per milliliter Standard Deviation 69.29
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 1 Day 22	124.87 micrograms per milliliter Standard Deviation 69.51	254.00 micrograms per milliliter Standard Deviation 97.45
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 2 Day 1	135.57 micrograms per milliliter Standard Deviation 125.10	367.75 micrograms per milliliter Standard Deviation 127.45
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 2 Day 15	167.80 micrograms per milliliter Standard Deviation 154.43	419.08 micrograms per milliliter Standard Deviation 351.57
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 3 Day 1	174.40 micrograms per milliliter Standard Deviation 184.70	500.98 micrograms per milliliter Standard Deviation 426.78
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 3 Day 15	193.50 micrograms per milliliter Standard Deviation 154.86	347.75 micrograms per milliliter Standard Deviation 259.68
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 4 Day 1	202.85 micrograms per milliliter Standard Deviation 172.75	344.30 micrograms per milliliter Standard Deviation 286.74
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 4 Day 15	184.85 micrograms per milliliter Standard Deviation 182.65	392.63 micrograms per milliliter Standard Deviation 322.70
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 5 Day 1	220.40 micrograms per milliliter Standard Deviation 228.54	608.00 micrograms per milliliter Standard Deviation 351.93
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 5 Day 15	233.00 micrograms per milliliter Standard Deviation 237.59	581.33 micrograms per milliliter Standard Deviation 356.35
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 6 Day 1	267.50 micrograms per milliliter Standard Deviation 280.72	665.67 micrograms per milliliter Standard Deviation 385.34
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 6 Day 15	160.60 micrograms per milliliter Standard Deviation 116.53	714.33 micrograms per milliliter Standard Deviation 451.44
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 7 Day 1	200.15 micrograms per milliliter Standard Deviation 165.25	611.67 micrograms per milliliter Standard Deviation 342.27
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 7 Day 15	254.50 micrograms per milliliter Standard Deviation 228.40	641.67 micrograms per milliliter Standard Deviation 246.78
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 8 Day 1	303.00 micrograms per milliliter Standard Deviation 278.60	874.67 micrograms per milliliter Standard Deviation 408.85
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 8 Day 15	242.50 micrograms per milliliter Standard Deviation 88.39	789.67 micrograms per milliliter Standard Deviation 525.08
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 9 Day 1	269.00 micrograms per milliliter Standard Deviation 147.08	722.67 micrograms per milliliter Standard Deviation 379.50
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 9 Day 15	444.00 micrograms per milliliter Standard Deviation 463.86	758.33 micrograms per milliliter Standard Deviation 393.20
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 10 Day 1	436.50 micrograms per milliliter Standard Deviation 441.94	941.67 micrograms per milliliter Standard Deviation 576.67
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 10 Day 15	684.00 micrograms per milliliter Standard Deviation 772.16	1224.67 micrograms per milliliter Standard Deviation 719.96
Phase 1: Trough Plasma Concentrations (Ctrough) of Isatuximab Cycle 11 Day 1	592.00 micrograms per milliliter	—