Skip to content
Triangle logo TriangleGet started
← Study library

NCT03194867 · REGISTRY CONDITION SEARCH

Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2024-06-14

Primary Objectives: * To evaluate the safety and tolerability of the combination of isatuximab (also known as SAR650984) and cemiplimab (also known as REGN2810) in patients with relapse/refractory multiple myeloma. * To compare the overall response of the combination of isatuximab and cemiplimab versus isatuximab alone in patients with RRMM based on International Myeloma Working Group (IMWG) criteria. Secondary Objectives: * To evaluate the efficacy as assessed by clinical benefit rate (CBR), duration of response (DOR), time to response (TTR), progression free survival (PFS), and overall survival (OS). * To assess the pharmacokinetics (PK) of isatuximab and cemiplimab when given in combination. * To assess the immunogenicity of isatuximab and cemiplimab when given in combination.

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

→

baseline

Baseline characteristics

→

outcome · POSTED

Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)

→

outcome · POSTED

Phase 1 and Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

→

outcome · POSTED

Phase 2: Percentage of Participants With Overall Response Rate (ORR)

→

outcome · POSTED

Phase 2: Percentage of Participants With Clinical Benefit Rate (CBR)

→

outcome · POSTED

Phase 2: Duration of Follow-up

→

outcome · POSTED

Phase 2: Duration of Response (DOR)

→

outcome · POSTED

Phase 2: Time to Response (TTR)

→

outcome · POSTED

Phase 2: Progression Free Survival (PFS)

→

outcome · POSTED

Phase 2: Overall Survival (OS)

→

outcome · POSTED

Phase 1 and 2: Plasma Concentration Observed at the End of IV Infusion (Ceoi) of Isatuximab Alone and in Combination With Cemiplimab

→

outcome · POSTED

Phase 1 and 2: Maximum Observed Concentration (Cmax) of Isatuximab Alone and in Combination With Cemiplimab

→

outcome · POSTED

Phase 1 and 2: Time to Reach Cmax (Tmax) of Isatuximab Alone and in Combination With Cemiplimab

→

outcome · POSTED

Phase 1 and 2: Last Concentration Observed Above the Lower Limit of Quantitation (Clast) of Isatuximab Alone and in Combination With Cemiplimab

→

outcome · POSTED

Phase 1 and 2: Time of Clast (Tlast) of Isatuximab Alone and in Combination With Cemiplimab

→

outcome · POSTED

Phase 1 and 2: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUClast) of Isatuximab Alone and in Combination With Cemiplimab

→

outcome · POSTED

Phase 1 and 2: AUC From Time 0 to Week 1 (AUC1week) of Isatuximab Alone and in Combination With Cemiplimab

→

outcome · POSTED

Phase 1 and 2: Number of Participants With Anti-Drug Antibodies (ADA) to Isatuximab

→

outcome · POSTED

Phase 1 and 2: Number of Participants With ADA to Cemiplimab

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
Inclusion criteria: * Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, as defined below: * Serum M-protein ≥1 g/dL (≥0.5 g/dL in case of immunoglobulin A \[IgA\] disease), AND/OR * Urine M-protein ≥200 mg/24 hours, OR * In the absence of measurable M-protein, serum immunoglobulin free light chain ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio (\<0.26 or \>1.65). * Patients must have received prior treatment with an immunomodulatory drug (IMiD) (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (PI) (for ≥2 cycles or ≥2 months of treatment). * Patients must have received at least 3 prior lines of therapy (Note: Induction therapy and stem cell transplant ± maintenance will be considered as one line). * Patient must have achieved MR or better with any anti-myeloma therapy (ie, primary refractory disease is not eligible). Exclusion criteria: * Prior exposure to isatuximab or participated clinical studies with isatuximab. * Prior exposure to any agent (approved or investigational) that blocks the programmed cell death-1 (PD-1)/PD-L1 pathway. * Evidence of other immune related disease/conditions. * History of non-infectious pneumonitis requiring steroids or current pneumonitis; history of the thoracic radiation. * Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. * Has allogenic haemopoietic stem cell (HSC) transplant. * Prior treatment with idelalisib (a PI3K inhibitor). * Eastern Cooperative Oncology Group (ECOG) performance status (PS) \>2. * Poor bone marrow reserve. * Poor organ function. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Isatuximab on Days 1, 8, 15, and 22, then Days 1 and 15 in 28-day cycles up to disease progression. Cemiplimab on Days 1 and 15 in 28-day cycle up to disease progression.
    intervention Names
    1. Drug: Isatuximab SAR650984
    2. Drug: Cemiplimab REGN2810
    label
    Isatuximab/cemiplimab (Regimen 1)
    type
    EXPERIMENTAL
  2. description
    Isatuximab on Days 1, 8, 15, and 22, then Days 1 and 15 in 28-day cycles up to disease progression. Cemiplimab on Day 1 in 28-day cycle up to disease progression.
    intervention Names
    1. Drug: Isatuximab SAR650984
    2. Drug: Cemiplimab REGN2810
    label
    Isatuximab/cemiplimab (Regimen 2)
    type
    EXPERIMENTAL
  3. description
    Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression.
    intervention Names
    1. Drug: Isatuximab SAR650984
    label
    Isatuximab
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Isatuximab
    2. Isatuximab/cemiplimab (Regimen 1)
    3. Isatuximab/cemiplimab (Regimen 2)
    description
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    name
    Isatuximab SAR650984
    other Names
    1. Sarclisa
    type
    DRUG
  2. arm Group Labels
    1. Isatuximab/cemiplimab (Regimen 1)
    2. Isatuximab/cemiplimab (Regimen 2)
    description
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    name
    Cemiplimab REGN2810
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
109
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Potential DLTs were defined as the occurrence of any of the following adverse reactions at first treatment cycle, unless due to disease progression or obviously unrelated cause: Hematological DLTs: Grade(G) 4 neutropenia (N) for more than 7 consecutive days, G3 to G4 N complicated by fever (temperature greater than or equal to \[\>=\] 38.5 degree Celsius on more than 1 occasion) or microbiologically/radiographically documented infection, G3 to G4 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention or Non-hematological DLTs: G4 non-hematologic AE, G\>=2 uveitis, G3 non-hematological AE lasting greater than (\>)3 days despite optimal care support, delay in initiation of Cycle 2 \>14 days due to treatment related laboratory abnormalities/AE. Any other AE that the investigator/study committee deemed to be dose-limiting, regardless of grade, was also considered as DLT.
    measure
    Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
    time Frame
    Cycle 1 Day 1 to Day 28
  2. description
    An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which did not necessarily have a causal relationship with study treatment. 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, was a medically important event. TEAEs were defined as an AE which occurred after the first dose of study treatment administration up to 30 days after the last dose of study treatment administration. The DLT observation period was 1 cycle (28 days). However, all AEs during treatment, unless due to disease progression or an obviously unrelated cause, were taken into consideration by the Study Committee for the determination of the maximum tolerated dose and recommended Phase 2 dose.
    measure
    Phase 1 and Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
    time Frame
    TEAEs were collected from the first dose up to 30 days after the last dose of study treatment, approximately 50 months
  3. description
    ORR by Investigator using international myeloma working group (IMWG) response criteria:percentage of participants with complete response (CR) (including stringent CR \[sCR\]very good partial response \[VGPR\] and partial response \[PR\]).CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,less than (\<)5% plasma cells in bone marrow (BM) aspirates and normal free light chain(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/24hour(h);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 \<200mg/24h.In addition to above, if present at baseline,\>=50% reduction in size (sum of products of maximal perpendicular diameters of measured lesions \[SPD\]) of soft tissue plasmacytomas required.
    measure
    Phase 2: Percentage of Participants With Overall Response Rate (ORR)
    time Frame
    From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
secondary Outcomes
  1. description
    CBR by Investigator using IMWG response criteria: percentage of participants with CR (including sCR), VGPR, PR (all defined in previous OM) or MR. MR was defined as \>= 25% but \<= 49% reduction in serum M-protein and reduction in 24h urine M-protein by 50-89%, which still exceeded 200 mg/24h; if present at baseline, \>=50% reduction in size (SPD) of soft tissue plasmacytomas was also required.
    measure
    Phase 2: Percentage of Participants With Clinical Benefit Rate (CBR)
    time Frame
    From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
  2. description
    Duration of follow-up was defined as the date of randomization to the date of last contact or death, whichever came first. Median duration of follow-up is reported.
    measure
    Phase 2: Duration of Follow-up
    time Frame
    From the date of randomization up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
  3. description
    DOR: Time from date of first response (\>=PR) that was subsequently confirmed to date of first documented progressive disease (PD) or death.DOR was determined only for participants who achieved a response of PR or better.If progression or death not observed, participant was censored at date of last valid disease assessment not showing disease progression performed prior to initiating further anticancer treatment and analysis cut-off date.PD(IMWG criteria):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 \>1cm in short axis,\>=50% increase in circulating plasma cells (minimum 200 cells/microliter\[c/mcL\]) if that was the only measure of disease. PR: as defined in OM3.
    measure
    Phase 2: Duration of Response (DOR)
    time Frame
    From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
  4. description
    TTR was defined as the time from randomization to first 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 24 hours urinary M-protein by \>=90% or to \<200 mg/24 hours. In addition to the above listed criteria, if present at baseline, a \>=50% reduction in the size SPD of soft tissue plasmacytomas was also required.
    measure
    Phase 2: Time to Response (TTR)
    time Frame
    From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
  5. description
    PFS: Time interval from the randomization date to the date of the first documented disease progression that is subsequently confirmed or the date of death due to any cause, whichever came first. If progression or death was not observed, participant was censored at date of last valid disease assessment not showing disease progression performed prior to initiation of a further anticancer treatment or the analysis cut-off date. Analysis was performed by Kaplan-Meier method. PD (IMWG) criteria: increase of \>=25% from lowest confirmed value in any 1 of following: serum M-protein (absolute increase \>=0.5g/dL), serum M-protein increase \>=1g/dL if lowest M component was \>=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 the longest diameter of a previous lesion \>1 cm in short axis or \>=50% increase in circulating plasma cells (minimum of 200 c/mcL) if that was the only measure of disease.
    measure
    Phase 2: Progression Free Survival (PFS)
    time Frame
    From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
  6. description
    OS was defined as the time interval 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 came first. The results provided below corresponds to descriptive OS information at the time of primary analysis completion date of 09 October 2019.
    measure
    Phase 2: Overall Survival (OS)
    time Frame
    From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
  7. description
    Plasma samples were collected at specified timepoints and those non-impacted by the bioanalytical issue were used for evaluation of Ceoi. It was calculated using non-compartmental analysis (NCA) after the first administration in Cycle 1. The PK population was defined independently for isatuximab and cemiplimab and consisted of all participants from the all-treated (AT) population with at least 1 available concentration post-baseline (whatever the cycle and even if dosing was incomplete) with adequate documentation of dosing and sampling dates and times.
    measure
    Phase 1 and 2: Plasma Concentration Observed at the End of IV Infusion (Ceoi) of Isatuximab Alone and in Combination With Cemiplimab
    time Frame
    At end of infusion (EOI) on Cycle 1 Day 1
  8. description
    Plasma samples were collected at specified timepoints and those non-impacted by the bioanalytical issue were used for evaluation of Cmax. It was calculated using NCA after the first administration in Cycle 1.
    measure
    Phase 1 and 2: Maximum Observed Concentration (Cmax) of Isatuximab Alone and in Combination With Cemiplimab
    time Frame
    At start of infusion (SOI), EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
  9. description
    Plasma samples were collected at specified timepoints and those non-impacted by the bioanalytical issue were used for evaluation of tmax. It was calculated using NCA after the first administration in Cycle 1.
    measure
    Phase 1 and 2: Time to Reach Cmax (Tmax) of Isatuximab Alone and in Combination With Cemiplimab
    time Frame
    At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
  10. description
    Plasma samples were collected at specified timepoints and those non-impacted by the bioanalytical issue were used for evaluation of Clast. It was calculated using NCA after the first administration in Cycle 1.
    measure
    Phase 1 and 2: Last Concentration Observed Above the Lower Limit of Quantitation (Clast) of Isatuximab Alone and in Combination With Cemiplimab
    time Frame
    At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
  11. description
    Plasma samples were collected at specified timepoints and those non-impacted by the bioanalytical issue were used for evaluation of tlast. It was calculated using NCA after the first administration in Cycle 1.
    measure
    Phase 1 and 2: Time of Clast (Tlast) of Isatuximab Alone and in Combination With Cemiplimab
    time Frame
    At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
  12. description
    AUClast was defined as the area under the plasma concentration versus time curve from time 0 to real time tlast calculated using the trapezoidal method over the dosing interval after the first administration in Cycle 1.
    measure
    Phase 1 and 2: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUClast) of Isatuximab Alone and in Combination With Cemiplimab
    time Frame
    At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
Full study description
brief Summary
Primary Objectives: * To evaluate the safety and tolerability of the combination of isatuximab (also known as SAR650984) and cemiplimab (also known as REGN2810) in patients with relapse/refractory multiple myeloma. * To compare the overall response of the combination of isatuximab and cemiplimab versus isatuximab alone in patients with RRMM based on International Myeloma Working Group (IMWG) criteria. Secondary Objectives: * To evaluate the efficacy as assessed by clinical benefit rate (CBR), duration of response (DOR), time to response (TTR), progression free survival (PFS), and overall survival (OS). * To assess the pharmacokinetics (PK) of isatuximab and cemiplimab when given in combination. * To assess the immunogenicity of isatuximab and cemiplimab when given in combination.
detailed Description
The duration of the study for a patient will include a period for screening of up to 21 days and 3-month post treatment follow up. The cycle duration is 28 days. Patients will continue treatment until disease progression, unacceptable adverse events, consent withdrawal, or any other reason.
Source references
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-1336d216cbd1bbff780dac70
      edge id
      nct-edge-9176c43ecfd62806f58d
      requested nct id
      NCT03194867
      primary nct id
      NCT03194867
      source kind
      ctgov_condition_query
      source record id
      Source null
      source file sha256
      2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
      payload sha256
      4b4f4bf23286c56b30898fe3e310f4c90028784a001e8e8b6c9ea2702528156d
      payload
      clinical indication matching status
      condition_index_match_asserted_by_registry_not_reviewed
      end exclusive
      true
      id
      nct-edge-9176c43ecfd62806f58d
      link basis
      returned_by_explicit_condition_and_posted_results_filter_query
      nct id
      NCT03194867
      occurrences
      1. context exact
        NCT03194867
        end
        11
        exact text
        NCT03194867
        start
        0
      offset unit
      unicode_code_points
      query cond
      Plasma Cell Neoplasms
      query disease state id
      ds-plasma-cell-neoplasms
      source file
      /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-plasma-cell-neoplasms-000.json
      source file sha256
      2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
      source json pointer
      /studies/42/protocolSection/identificationModule/nctId
      source kind
      ctgov_condition_query
      source record id
      Source null
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      7f34d38ad5924ccd903093adeffc0b828f59eb8faa27d99d769f4573fc4665c5

    Preserved source evidence · Not medical advice