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NCT02812706: Islands

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

Completed Phase 1, PHASE2 Results posted Last updated 1 April 2024
What this trial tests

Phase 1, PHASE2 trial testing Isatuximab SAR650984 in Multiple Myeloma in 36 participants. Completed in 28 September 2022.

Timeline
5 September 2016
Primary endpoint
31 July 2018
28 September 2022

Quick facts

Lead sponsorSanofi
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment36
Start date5 September 2016
Primary completion31 July 2018
Estimated completion28 September 2022
Sites13 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Sanofi — full company profile →

Who can join

20 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Primary · Cycle 1 (28 days)

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 nause

GroupValue95% CI
Phase 1, Cohort 1: Isatuximab 10 mg/kg0
Phase 1, Cohort 2: Isatuximab 20 mg/kg0
Phase 2: Percentage of Participants With Overall Response (OR) Primary · 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)

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 leve

GroupValue95% CI
Phase 2: Isatuximab 20 mg/kg32.1
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Secondary · 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)

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,

TEAEs
GroupValue95% CI
Phase 1, Cohort 1: Isatuximab 10 mg/kg3
Phase 1, Cohort 2: Isatuximab 20 mg/kg4
TESAEs
GroupValue95% CI
Phase 1, Cohort 1: Isatuximab 10 mg/kg1
Phase 1, Cohort 2: Isatuximab 20 mg/kg2
Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Secondary · 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)

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,

TEAEs
GroupValue95% CI
Phase 2: Isatuximab 20 mg/kg25
TESAEs
GroupValue95% CI
Phase 2: Isatuximab 20 mg/kg11
Phase 1: Percentage of Participants With Overall Response (OR) Secondary · 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)

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% reduct

GroupValue95% CI
Phase 1, Cohort 1: Isatuximab 10 mg/kg66.7
Phase 1, Cohort 2: Isatuximab 20 mg/kg60.0
Phase 1: Duration of Response (DOR) Secondary · 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)

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-p

GroupValue95% CI
Phase 1, Cohort 1: Isatuximab 10 mg/kg100.64± 7.78
Phase 1, Cohort 2: Isatuximab 20 mg/kg113.90± 18.45
Phase 2: Percentage of Participants With Clinical Benefit (CB) Secondary · 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)

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-

GroupValue95% CI
Phase 2: Isatuximab 20 mg/kg53.6
Phase 2: Overall Survival (OS) Secondary · From date of first study treatment administration to the date of death due to any cause (maximum duration of exposure: up to 248 weeks)

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.

GroupValue95% CI
Phase 2: Isatuximab 20 mg/kgNA20.24 – NA
Phase 2: Progression Free Survival (PFS) Secondary · 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)

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

GroupValue95% CI
Phase 2: Isatuximab 20 mg/kg5.63.75 – 12.98
Phase 2: Duration of Response (DOR) Secondary · 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)

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

GroupValue95% CI
Phase 2: Isatuximab 20 mg/kg58.70± 29.91
Phase 2: Time to Progression (TTP) Secondary · 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)

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

GroupValue95% CI
Phase 2: Isatuximab 20 mg/kg5.53.745 – 12.977
Phase 1: Plasma Concentration Observed at the End of Intravenous Infusion (Ceoi) of Isatuximab Secondary · End of infusion on Day 1 of Cycle 1

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

GroupValue95% CI
Phase 1, Cohort 1: Isatuximab 10 mg/kg122± 21.6
Phase 1, Cohort 2: Isatuximab 20 mg/kg246± 51.8

Adverse events — posted to ClinicalTrials.gov

Time frame: AE data was collected from first dose of study drug up to 30 days after last dose of study drug administration (maximum duration of exposure: up to 112 weeks for Cohort 1, and 137 weeks for Cohort 2 for Phase 1 part; and up to 248 weeks for Phase 2 part). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1, Cohort 1: Isatuximab 10 mg/kg
Serious: 1/3 (33%)
Deaths: 1/3
Phase 1, Cohort 2: Isatuximab 20 mg/kg
Serious: 2/5 (40%)
Deaths: 2/5
Phase 2: Isatuximab 20 mg/kg
Serious: 11/28 (39%)
Deaths: 10/28

Serious adverse events (23 terms)

ReactionSystemPhase 1, Cohort 1: Isatuxi…Phase 1, Cohort 2: Isatuxi…Phase 2: Isatuximab 20 mg/kg
PneumoniaInfections and infestations
Disseminated Intravascular CoagulationBlood and lymphatic system disorders
CataractEye disorders
IleusGastrointestinal disorders
Large Intestine PolypGastrointestinal disorders
Disease ProgressionGeneral disorders
Non-Cardiac Chest PainGeneral disorders
Anal AbscessInfections and infestations
Intervertebral DiscitisInfections and infestations
Lung InfectionInfections and infestations
SinusitisInfections and infestations
Diabetic KetoacidosisMetabolism and nutrition disorders
Osteonecrosis Of JawMusculoskeletal and connective tissue disorders
Synovial CystMusculoskeletal and connective tissue disorders
Breast CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal CarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DiplegiaNervous system disorders
SeizureNervous system disorders
Subarachnoid HaemorrhageNervous system disorders
Thrombotic Cerebral InfarctionNervous system disorders
NephrolithiasisRenal and urinary disorders
Neurogenic BladderRenal and urinary disorders
Deep Vein ThrombosisVascular disorders
Other adverse events (47 terms — click to expand)

ReactionSystemPhase 1, Cohort 1: Isatuxi…Phase 1, Cohort 2: Isatuxi…Phase 2: Isatuximab 20 mg/kg
Infusion Related ReactionInjury, poisoning and procedural complications
NasopharyngitisInfections and infestations
PyrexiaGeneral disorders
DiarrhoeaGastrointestinal disorders
Back PainMusculoskeletal and connective tissue disorders
InfluenzaInfections and infestations
CataractEye disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
Oedema PeripheralGeneral disorders
BronchitisInfections and infestations
Herpes ZosterInfections and infestations
PharyngitisInfections and infestations
LeukopeniaBlood and lymphatic system disorders
Decreased AppetiteMetabolism and nutrition disorders
InsomniaPsychiatric disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Nasal CongestionRespiratory, thoracic and mediastinal disorders
Rhinitis AllergicRespiratory, thoracic and mediastinal disorders
Upper Respiratory Tract InflammationRespiratory, thoracic and mediastinal disorders
HaemorrhoidsGastrointestinal disorders
Periodontal DiseaseGastrointestinal disorders
StomatitisGastrointestinal disorders
VomitingGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Chest DiscomfortGeneral disorders
ChillsGeneral disorders
Procedural PainInjury, poisoning and procedural complications
ConjunctivitisInfections and infestations
Hand-Foot-And-Mouth DiseaseInfections and infestations
Infected Dermal CystInfections and infestations
PneumoniaInfections and infestations
SinusitisInfections and infestations
Upper Respiratory Tract InfectionInfections and infestations
AnaemiaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
HyperkalaemiaMetabolism and nutrition disorders
VertigoEar and labyrinth disorders
Hot FlushVascular disorders

Most-reported serious reactions: Pneumonia, Disseminated Intravascular Coagulation, Cataract, Ileus, Large Intestine Polyp, Disease Progression, Non-Cardiac Chest Pain, Anal Abscess.

Data from ClinicalTrials.gov NCT02812706 adverse events section.

Sponsor's own description

Primary Objectives: * Phase I: To evaluate safety and tolerability of isatuximab in Japanese participants with relapsed and refractory multiple myeloma. * Phase II: To evaluate efficacy of isatuximab at recommended dose and to further evaluate the overall response rate (ORR) of isatuximab in Japanese participants with relapsed and refractory multiple myeloma. Secondary Objectives: * To evaluate the safety including immunogenicity of isatuximab. The severity, frequency and incidence of all adverse events were assessed. * To evaluate the pharmacokinetic (PK) profile of isatuximab in the proposed dosing schedule. * To assess the efficacy using International Myeloma Working Group (IMWG) uniform response criteria. * To assess the relationship between Baseline cluster of differentiation 38 (CD38) receptor density on multiple myeloma cells and efficacy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function.
    Vigano S, Alatzoglou D, Irving M, Ménétrier-Caux C, et al · · 2019 · cited 326× · PMID 31244820 · DOI 10.3389/fimmu.2019.00925
  2. Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts.
    Wang Y, Zhang H, Liu C, Wang Z, et al · · 2022 · cited 179× · PMID 35978433 · DOI 10.1186/s13045-022-01325-0
  3. Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab.
    Martin TG, Corzo K, Chiron M, Velde HV, et al · · 2019 · cited 103× · PMID 31779273 · DOI 10.3390/cells8121522
  4. A look backward and forward in the regulatory and treatment history of multiple myeloma: Approval of novel-novel agents, new drug development, and longer patient survival.
    Kazandjian D, Landgren O. · · 2016 · cited 53× · PMID 28061986 · DOI 10.1053/j.seminoncol.2016.10.008
  5. Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update.
    Abramson HN. · · 2018 · cited 42× · PMID 30544512 · DOI 10.3390/ijms19123924
  6. Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study.
    Sunami K, Suzuki K, Ri M, Matsumoto M, et al · · 2020 · cited 12× · PMID 32975869 · DOI 10.1111/cas.14657
  7. Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application.
    Wang R, Liu Z, Wang T, Zhang J, et al · · 2024 · cited 7× · PMID 38348050 · DOI 10.3389/fimmu.2024.1320244
  8. Model-based simulation to support the approval of isatuximab alone or with dexamethasone for the treatment of relapsed/refractory multiple myeloma in Japanese patients.
    Thai HT, Koiwai K, Shitara Y, Kazama H, et al · · 2023 · cited 3× · PMID 37002644 · DOI 10.1002/psp4.12947

Verify or expand the search:

Other trials of Isatuximab SAR650984

Trials testing the same drug.

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Trials by the same sponsor.

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