NCT05405166 · CITED IN SOURCE DOCUMENTS

SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-09-02

This will be randomized, multicenter, Phase 3, open-label study evaluating subcutaneous (SC) vs intravenous (IV) administration of isatuximab in combination with pomalidomide and dexamethasone (Pd) in RRMM patients (study participants) who will receive at least 1 prior line of therapy including lenalidomide and a proteasome inhibitor (PI). Eligible participants were randomized 1:1 into 1 of 2 study arms: Arm SC: Isatuximab SC + Pd Arm IV: Isatuximab IV + Pd Participants are allowed to continue therapy until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Observed Concentration Before Dosing (Ctrough) of Isatuximab at Steady State

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outcome · POSTED

Very Good Partial Response or Better Rate

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outcome · POSTED

Ctrough of Isatuximab at 4 Weeks (CT4W)

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outcome · POSTED

Percentage of Participants With Infusion Reactions

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outcome · POSTED

Percentage of Participants Who Responded Very Satisfied and Satisfied to the 'Patient Experience and Satisfaction Questionnaire (PESQ-FU)': Satisfaction With Injection Method' (Item-8) at Cycle 5 Day 15

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Time to First Response (TT1R)

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outcome · POSTED

Time to Best Response (TTBR)

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outcome · POSTED

Progression-free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression Free Survival 2 (PFS2)

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outcome · POSTED

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

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outcome · POSTED

Isa-SC + Pd: Number of Participants With Injection Site Reactions (ISRs)

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outcome · POSTED

Ctrough of Isatuximab

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outcome · POSTED

Isa-SC + Pd: Percentage of Successful Injections With Isatuximab Injector Device

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outcome · POSTED

Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Isatuximab

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outcome · POSTED

Percentage of Participants With Response to 'Patient Expectation Questionnaire at Baseline (PEQ-BL)'

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outcome · POSTED

Percentage of Participants Who Disagreed and Strongly Disagreed to 'PESQ-FU: Discomfort With Injection Method'

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outcome · POSTED

Percentage of Participants Who Disagreed and Strongly Disagreed to 'PESQ-FU: Pain With Injection Method'

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outcome · POSTED

Percentage of Participants Who Disagreed and Strongly Disagreed to 'PESQ-FU: Side Effects With Injection Method'

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outcome · POSTED

Percentage of Participants Who Strongly Agreed and Agreed to 'PESQ-FU: Time Saving With Injection Method'

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outcome · POSTED

Percentage of Participants Who Responded Very Satisfied and Satisfied to 'PESQ-FU: Satisfaction With Injection Method'

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outcome · POSTED

Percentage of Participants Who Disagreed and Strongly Disagreed to 'PESQ-FU: Side Effects With Study Medication'

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outcome · POSTED

Percentage of Participants Who Strongly Agreed and Agreed to 'PESQ-FU: Study Medication Worth Taking'

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outcome · POSTED

Percentage of Participants Who Responded Very Satisfied and Satisfied to 'PESQ-FU: Satisfaction With Study Medication'

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outcome · POSTED

Percentage of Participants Who Responded Definitely Yes and Probably Yes to 'PESQ-FU: Recommendation of Study Medication'

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outcome · POSTED

Percentage of Participants With Response to 'Patient Experience and Satisfaction End of Treatment Questionnaire (PESQ-EOT)'

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outcome · POSTED

Participant Responses to Patient's Assessment of Treatment (PAT) Questionnaire

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outcome · POSTED

Health Resource Utilization and Productivity Questionnaire (HRUPQ): Baseline Healthcare Utilization: Number of Times in the Past 6 Months a Participant Received Care

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outcome · POSTED

HRUPQ: Baseline Healthcare Utilization: Number of Nights in the Past 6 Months a Participant Stayed in Hospital

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outcome · POSTED

HRUPQ: Baseline Healthcare Utilization: Number of Times in the Past 6 Months a Participant Consulted a Healthcare Professional (HCP)

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outcome · POSTED

Duration of Hospital Visits for Treatment Administration and Duration of Post-Treatment Monitoring Based on HRUPQ

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outcome · POSTED

Percentage of Participants Who Visited Healthcare Professional for Non-trial-related Health Issues Based on HRUPQ

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outcome · POSTED

Percentage of Participants Who Ever Retired During the Study Based on HRUPQ

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outcome · POSTED

Percentage of Participants Who Retired Early Due to MM Based on HRUPQ

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outcome · POSTED

Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QoL)

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Physical Functioning

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Role Functioning

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Emotional Functioning

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Cognitive Functioning

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Social Functioning

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Fatigue

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Nausea and Vomiting

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Pain

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Dyspnea

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Insomnia

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Appetite Loss

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Constipation

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Diarrhea

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outcome · POSTED

Change From Baseline in EORTC QLQ-C30: Financial Difficulties

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outcome · POSTED

Change From Baseline in EORTC QLQ-Myeloma Module (MY20): Disease Symptoms

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outcome · POSTED

Change From Baseline in EORTC QLQ-MY20: Side Effects of Treatment

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outcome · POSTED

Change From Baseline in EORTC QLQ-MY20: Future Perspective

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outcome · POSTED

Change From Baseline in EORTC QLQ-MY20: Body Image

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outcome · POSTED

Change From Baseline in European Quality of Life Group Measure With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Visual Analogue Scale (VAS)

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outcome · POSTED

ORR Based on at Least 1 Chromosomal Abnormality

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Participants with multiple myeloma who have received at least one prior line of anti-myeloma therapy, which must include lenalidomide and a proteasome inhibitor given alone or in combination. * Measurable serum M-protein (≥ 0.5 g/dL) and/or urine M-protein (≥ 200 mg/24 hours) and/or serum free light chain (FLC) assay (Involved FLC assay ≥10 mg/dL and abnormal serum FLC ratio (\<0.26 or \>1.65)). Exclusion Criteria: * Primary refractory multiple myeloma participants * Participants with prior anti-CD38 treatment: (a) administered less than 9 months before randomization or, (b) intolerant to the anti-CD38 previously received * Prior therapy with pomalidomide * Participants with inadequate biological tests. * Significant cardiac dysfunction * Participants diagnosed or treated for another malignancy within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, and in situ malignancy, or low risk prostate cancer after curative therapy * Concomitant plasma cell leukemia * Active primary amyloid light -chain amyloidosis * Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment * Know active Hepatitis A infection. Current active or chronic hepatitis B (HBV) or hepatitis C (HCV) infection. Participants with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed. * Women of childbearing potential or male participant with women of childbearing potential who do not agree to use highly effective method of birth control The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Isatuximab dose will administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication.
intervention Names
Drug: Isatuximab SC
Drug: Dexamethasone
Drug: Pomalidomide
Drug: Montelukast
Drug: Paracetamol / Acetaminophen
Drug: Diphenhydramine
Drug: Methylprednisolone
label
Isatuximab Subcutaneous (SC)
type
EXPERIMENTAL
description
Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication.
intervention Names
Drug: Isatuximab IV
Drug: Dexamethasone
Drug: Pomalidomide
Drug: Montelukast
Drug: Paracetamol / Acetaminophen
Drug: Diphenhydramine
Drug: Methylprednisolone
label
Isatuximab Intravenous (IV)
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Isatuximab Intravenous (IV)
description
Pharmaceutical form: Concentrate solution for IV infusion; Route of administration: Intravenous
name
Isatuximab IV
other Names
SAR650984
SARCLISA®
type
DRUG
arm Group Labels
Isatuximab Subcutaneous (SC)
description
Pharmaceutical form: Solution for subcutaneous administration; Route of administration: Subcutaneous (SC)
name
Isatuximab SC
other Names
SAR650984
type
DRUG
arm Group Labels
Isatuximab Intravenous (IV)
Isatuximab Subcutaneous (SC)
description
Pharmaceutical form: Tablet; Route of administration: Oral
name
Dexamethasone
type
DRUG
arm Group Labels
Isatuximab Intravenous (IV)
Isatuximab Subcutaneous (SC)
description
Pharmaceutical form: hard capsules; Route of administration: Oral
name
Pomalidomide
other Names
Pomalyst or equivalent
type
DRUG
arm Group Labels
Isatuximab Intravenous (IV)
Isatuximab Subcutaneous (SC)
description
Pharmaceutical form: As per local commercial product; Route of administration: Oral; Auxiliary Medicinal Product (AxMP) i.e., background treatment; ATC code: H02AB02
name
Dexamethasone
type
DRUG
arm Group Labels
Isatuximab Intravenous (IV)
Isatuximab Subcutaneous (SC)
description
Pharmaceutical form: As per local commercial product; Route of administration: Oral; AxMP i.e., background treatment; ATC code: R03DC03
name
Montelukast
type
DRUG
arm Group Labels
Isatuximab Intravenous (IV)
Isatuximab Subcutaneous (SC)
description
Pharmaceutical form: As per local commercial product; Route of administration: Oral; AxMP i.e., background treatment; ATC code: N02BE01
name
Paracetamol / Acetaminophen
type
DRUG
arm Group Labels
Isatuximab Intravenous (IV)
Isatuximab Subcutaneous (SC)
description
Pharmaceutical form: As per local commercial product; Route of administration: As premedication- oral; for management of infusion reactions-IV (or oral equivalent); AxMP i.e., background treatment and rescue medication (in case of infusion reactions); ATC code: R06AA02
name
Diphenhydramine
type
DRUG
arm Group Labels
Isatuximab Intravenous (IV)
Isatuximab Subcutaneous (SC)
description
Pharmaceutical form: As per local commercial product; Route of administration: As premedication-IV; for management of infusion reactions- IV (or oral equivalent); AxMP i.e., background treatment and rescue medication (in case of infusion reactions); ATC code: H02AB04
name
Methylprednisolone
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 531
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
ORR by independent review committee (IRC) using 2016 international myeloma working group (IMWG) criteria:Percentage of participants with complete response (CR),stringent CR (sCR),very good partial response (VGPR) \& partial response (PR).CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas (STP),\<5% plasma cells in bone marrow (BM) aspirates \& a normal free light chain(FLC)ratio (0.26-1.65).sCR:CR plus no clonal cells in BM biopsy. VGPR:serum \& urine M-protein detectable by immunofixation, not electrophoresis;\>=90% reduction in serum M-protein plus urine M-protein level\<100mg/24hour(h);\>=90% decrease in sum of maximal perpendicular diameter (SPD) compared to baseline in STP;FLC only:\>=90% decrease in difference between involved and uninvolved FLC levels.PR:\>=50% reduction of serum M-protein and reduction in 24h urine M-protein by \>=90% or to \<200mg/24h.In addition to above, if present at baseline,\>=50% reduction in size SPD of STPs also required.
measure
Overall Response Rate (ORR)
time Frame
From first dose of study medication administration (Day 1) up to PCD (06-Nov-2024), approximately 28 months
description
Ctrough at steady state was the observed plasma concentration collected on pre-dose at Cycle 6 Day 1 (equivalent to prior to Cycle 6 Day 1) of isatuximab administration dose.
measure
Observed Concentration Before Dosing (Ctrough) of Isatuximab at Steady State
time Frame
Pre-dose at Cycle 6 Day 1

secondary Outcomes

description
VGPR or better rate by IRC using 2016 IMWG criteria: Percentage of participants with sCR, CR, and VGPR. CR: negative immunofixation on serum and urine, disappearance of any STP, \<5% plasma cells in BM aspirates \& normal FLC ratio (0.26-1.65). sCR: CR plus no clonal cells in BM biopsy. VGPR: serum and urine M-protein detectable by immunofixation, not electrophoresis;\>=90% reduction in serum M-protein plus urine M-protein level\<100mg/24h;\>=90% decrease in SPD compared to baseline in STP; FLC only:\>=90% decrease in difference between involved and uninvolved FLC levels. Percentages are rounded off to the tenth decimal place.
measure
Very Good Partial Response or Better Rate
time Frame
From first dose of study medication administration (Day 1) up to DCO date (29-Aug-2025), approximately 38 months
description
The CT4W was the observed plasma concentrations collected on pre-dose at Cycle 2 Day 1 (equivalent to prior to Cycle 2 Day 1) of isatuximab administration dose.
measure
Ctrough of Isatuximab at 4 Weeks (CT4W)
time Frame
Pre-dose at Cycle 2 Day 1 (at 4 weeks)
description
Infusion reactions were graded using National Cancer Institute-Common Terminology Criteria for AE (NCI-CTCAE) version (v)5.0 criteria: Grade 1: mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2: moderate reaction; therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for \<=24 hours. Grade 3/4: severe or life-threatening reaction (Grade 3: prolonged \[not rapidly responsive to symptomatic medication and/or brief interruption of infusion\]; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4: life-threatening consequences; urgent intervention indicated). Percentage of participants who observed AE of infusion reactions were collected through the electronic case report form (eCRF) as assessed by investigators. Percentages are rounded off to the tenth decimal place.
measure
Percentage of Participants With Infusion Reactions
time Frame
From first dose of study medication (Day 1) up to 30 days after the last dose of study medication, approximately 38 months
description
The PESQ-FU consisting of 9 items has been designed to follow up on participant experience and satisfaction regarding the injection method (discomfort, pain, side effects, time saving and satisfaction) and study medication (side effects, worth taking, satisfaction and recommendation). This questionnaire has been adapted based on qualitative interviews with oncology participants. The responses to 'satisfaction with injection method' were recorded as 'very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied and very dissatisfied' at specified timepoints. The total percentage of participants who were very satisfied and satisfied with the injection method (item-8) at Cycle 5 Day 15 is reported here. Percentages are rounded off to the tenth decimal place.
measure
Percentage of Participants Who Responded Very Satisfied and Satisfied to the 'Patient Experience and Satisfaction Questionnaire (PESQ-FU)': Satisfaction With Injection Method' (Item-8) at Cycle 5 Day 15
time Frame
Cycle 5 Day 15
description
DOR: Time from the date of first response to the date of first occurrence of progressive disease (PD) determined by IRC or death from any cause, whichever occurred first.DOR was determined only for participants who achieved a response (PR or better).If PD/death not observed, participant was censored at date of last valid disease assessment performed prior to initiating further anti-myeloma treatment or analysis cut-off date, whichever occurred first. As per IMWG criteria: PD: increase of \>=25% from lowest confirmed value in any 1 of following: serum M-protein (absolute increase\>=0.5 gram/deciliter\[g/dL\]),serum M-protein increase\>=1g/dL if lowest M-component \>=5g/dL, urine M-component (absolute increase \>=200mg/24h), appearance of new lesion(s),\>=50% increase from nadir in SPD of \>1 lesion or \>=50% increase in longest diameter of a previous lesion \>1 centimeter (cm) in short axis. PR: as defined in OM1.
measure
Duration of Response (DOR)
time Frame
From first dose of study medication administration (Day 1) up to DCO date (29-Aug-2025), approximately 38 months
description
TT1R was defined as the time from randomization to the date of first IRC determined response (PR or better) that was subsequently confirmed. PR as per IMWG criteria was defined as \>=50% reduction of serum M-protein and reduction in 24h urine M-protein by \>=90% or to \<200mg/24h. In addition to above, if present at baseline, \>=50% reduction in the size SPD of STPs was also required.
measure
Time to First Response (TT1R)
time Frame
From first dose of study medication administration (Day 1) up to DCO date (29-Aug-2025), approximately 38 months
description
TTBR was defined as the time from randomization to the date of first occurrence of IRC determined best overall response (PR or better) that was subsequently confirmed. PR as per IMWG criteria was defined as \>=50% reduction of serum M-protein and reduction in 24h urine M-protein by \>=90% or to \<200mg/24h. In addition to above, if present at baseline,\>=50% reduction in the size SPD of STPs was also required.
measure
Time to Best Response (TTBR)
time Frame
From first dose of study medication administration (Day 1) up to DCO date (29-Aug-2025), approximately 38 months
description
PFS was defined as the time from the date of randomization to the date of first documentation of PD as determined by IRC or the date of death from any cause, whichever came first. Responses were determined according to IMWG criteria. PFS was censored at the date of the last valid disease assessment not showing PD performed prior to initiation of a further anti-myeloma treatment (if any) or the analysis cut-off date, whichever came first.
measure
Progression-free Survival (PFS)
time Frame
From first dose of study medication administration (Day 1) up to DCO date (29-Aug-2025), approximately 38 months
description
OS was defined as the time from the date of randomization to death from any cause. Participants without death prior to the analysis cut-off date were censored at the last date the participant was known to be alive or the cut-off date, whichever was first.
measure
Overall Survival (OS)
time Frame
From first dose of study medication administration (Day 1) up to DCO date (29-Aug-2025), approximately 38 months
description
PFS2 was defined as time from the date of randomization to the date of first documentation of PD (as assessed by Investigator) after initiation of further anti-myeloma treatment or death from any cause, whichever happened first. Same censoring rule applies as in the PFS endpoint.
measure
Progression Free Survival 2 (PFS2)
time Frame
From first dose of study medication administration (Day 1) up to DCO date (29-Aug-2025), approximately 38 months
description
An AE was defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. SAEs were 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 or was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.
measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
time Frame
From first dose of study medication (Day 1) up to 30 days after the last dose of study medication, approximately 38 months
description
The ISRs are defined as AEs related to medication administration with onset typically within 24 hours from the start of the infusion and are graded using NCI-CTCAE v5.0 criteria: Grade 1: tenderness with or without associated symptoms (warmth, erythema, itching). Grade 2: pain; lipodystrophy; edema; phlebitis. Grade 3: ulceration or necrosis severe tissue damage operative intervention indicated. Grade 4: life-threatening consequences; urgent intervention indicated. ISRs were collected through the eCRF. Number of participants with at least 1 ISR is reported. ISRs were applicable only for the SC administration.
measure
Isa-SC + Pd: Number of Participants With Injection Site Reactions (ISRs)
time Frame
From first dose of study medication (Day 1) up to 30 days after the last dose of study medication, approximately 38 months

Full study description

brief Summary: This will be randomized, multicenter, Phase 3, open-label study evaluating subcutaneous (SC) vs intravenous (IV) administration of isatuximab in combination with pomalidomide and dexamethasone (Pd) in RRMM patients (study participants) who will receive at least 1 prior line of therapy including lenalidomide and a proteasome inhibitor (PI). Eligible participants were randomized 1:1 into 1 of 2 study arms: Arm SC: Isatuximab SC + Pd Arm IV: Isatuximab IV + Pd Participants are allowed to continue therapy until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.
detailed Description: Two study arms are treated in 4-week cycles until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.

Source references

references

citation
Ailawadhi S, Spicka I, Spencer A, Lu J, Oriol A, Ling S, Schjesvold F, Berkovits A, Hus M, Li C, Dimopoulos MA, Rajnics P, Besisik SK, Hungria V, Custidiano MDR, Parmar G, Leleu X, Li F, Cerchione C, Gomez C, Ishida T, Mateos MV, Buck TT, LeBlanc R, Minarik J, Goldschmidt H, Zhang R, Semiond D, Suzan F, Stefanova-Urena M, Koch V, Moreau P. Isatuximab Subcutaneous by On-Body Injector Versus Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase III IRAKLIA Study. J Clin Oncol. 2025 Aug;43(22):2527-2537. doi: 10.1200/JCO-25-00744. Epub 2025 Jun 3.
pmid
40459178
type
DERIVED