Plasma Cell MyelomaPhase 1/2NCT03194867
Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
A Phase 1/2 study testing Isatuximab SAR650984 and Cemiplimab REGN2810 in people with Plasma Cell Myeloma, run by Sanofi at 30 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Plasma Cell Myeloma
- What is being tested?
- Isatuximab SAR650984 and Cemiplimab REGN2810
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 30 sitesin 10 countries
- Study dates
- 21 Feb 2018to 5 Apr 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
30 sites in 10 countries.
30 sites in 10 countries
Spain5 sites
Investigational Site Number :7240004
Badalona, Catalunya [Cataluña], 08916
Investigational Site Number :7240003
Barcelona, Barcelona [Barcelona], 08035
Investigational Site Number :7240002
Barcelona, Catalunya [Cataluña], 08036
Investigational Site Number :7240006
Madrid, 28041
Investigational Site Number :7240005
Valencia, Valenciana, Comunidad, 46017
United States4 sites
University of Colorado-Site Number:8400001
Denver, Colorado, 80262
University of Kansas Medical Center-Site Number:8400003
Kansas City, Kansas, 66160-7321
Memorial Sloan-Kettering Cancer Center-Site Number:8400002
New York, New York, 10021
Fox Chase Cancer Center-Site Number:8400004
Philadelphia, Pennsylvania, 19111
France4 sites
Investigational Site Number :2500004
Lille, 59037
Investigational Site Number :2500002
Nantes, 44093
Investigational Site Number :2500003
Pierre-Bénite, 69495
Investigational Site Number :2500001
Villejuif, 94800
Australia3 sites
Investigational Site Number :0360002
Richmond, Victoria, 3121
Investigational Site Number :0360001
West Perth, Western Australia, 6005
Investigational Site Number :0360003
Wollongong, New South Wales, 2500
Brazil3 sites
Investigational Site Number :0760003
Goiânia, Goiás, 74605-020
Investigational Site Number :0760001
Porto Alegre, Rio Grande do Sul, 90110-270
Investigational Site Number :0760004
São Paulo, São Paulo, 01236030
Canada3 sites
Investigational Site Number :1240001
Montreal, Quebec, H1T 2M4
Investigational Site Number :1240005
Montreal, Quebec, H4J 1C5
Investigational Site Number :1240003
Sherbrooke, Quebec, J1H 5N4
Czechia3 sites
Investigational Site Number :2030002
Brno, 62500
Investigational Site Number :2030003
Ostrava - Poruba, 70852
Investigational Site Number :2030001
Prague, 12808
Italy3 sites
Investigational Site Number :3800003
Brescia, 25123
Investigational Site Number :3800005
Rozzano, Milano, 20089
Investigational Site Number :3800001
Torino, 10126
About this study
Official title: A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics and Efficacy of Isatuximab in Combination With Cemiplimab in Patients With Relapsed/Refractory Multiple Myeloma
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.
Read more
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.
Read the 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.
- Conditions
- Plasma Cell Myeloma
- Being tested
- Isatuximab SAR650984, Cemiplimab REGN2810
- Keywords
- Anti-CD38 monoclonal antibody
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isatuximab SAR650984Drug
Also called Sarclisa
Pharmaceutical form: solution for infusion
Route of administration: intravenous
Cemiplimab REGN2810Drug
Pharmaceutical form: solution for infusion
Route of administration: intravenous
| Study group | Role | What they receive |
|---|---|---|
| Isatuximab/cemiplimab (Regimen 1) | Experimental | 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. Receives: Drug: Isatuximab SAR650984; Drug: Cemiplimab REGN2810 |
| Isatuximab/cemiplimab (Regimen 2) | Experimental | 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. Receives: Drug: Isatuximab SAR650984; Drug: Cemiplimab REGN2810 |
| Isatuximab | Active comparator | Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression. Receives: Drug: Isatuximab SAR650984 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
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.
Measured: Cycle 1 Day 1 to Day 28
Phase 1 and Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
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.
Measured: TEAEs were collected from the first dose up to 30 days after the last dose of study treatment, approximately 50 months
Phase 2: Percentage of Participants With Overall Response Rate (ORR)
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.
Measured: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
Secondary outcomes (15)
Phase 2: Percentage of Participants With Clinical Benefit Rate (CBR)
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.
Measured: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
Phase 2: Duration of Follow-up
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.
Measured: From the date of randomization up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
Phase 2: Duration of Response (DOR)
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.
Measured: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
Phase 2: Time to Response (TTR)
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.
Measured: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
Phase 2: Progression Free Survival (PFS)
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.
Measured: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
Phase 2: Overall Survival (OS)
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.
Measured: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
Phase 1 and 2: Plasma Concentration Observed at the End of IV Infusion (Ceoi) of Isatuximab Alone and in Combination With Cemiplimab
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.
Measured: At end of infusion (EOI) on Cycle 1 Day 1
Phase 1 and 2: Maximum Observed Concentration (Cmax) of Isatuximab Alone and in Combination With Cemiplimab
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.
Measured: At start of infusion (SOI), EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
Phase 1 and 2: Time to Reach Cmax (Tmax) of Isatuximab Alone and in Combination With Cemiplimab
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.
Measured: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
Phase 1 and 2: Last Concentration Observed Above the Lower Limit of Quantitation (Clast) of Isatuximab Alone and in Combination With Cemiplimab
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.
Measured: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
Phase 1 and 2: Time of Clast (Tlast) of Isatuximab Alone and in Combination With Cemiplimab
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.
Measured: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
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
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.
Measured: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
Phase 1 and 2: AUC From Time 0 to Week 1 (AUC1week) of Isatuximab Alone and in Combination With Cemiplimab
AUC1week was defined as the area under the plasma concentration versus time curve from time 0 to 1 week post dose calculated using the trapezoidal method over the dosing interval after the first administration in Cycle 1.
Measured: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
Phase 1 and 2: Number of Participants With Anti-Drug Antibodies (ADA) to Isatuximab
ADA responses were categorized as treatment-induced ADA and treatment boosted ADA. Pre-existing ADA was defined as ADA that were present in samples drawn during the pre-treatment period. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without pre-existing ADA. Treatment boosted ADA was defined as pre-existing ADAs with a significant increase in the ADA titer during the study compared to the Baseline titer. The ADA evaluable population was defined independently for isatuximab and cemiplimab and consisted of all participants from AT population with at least 1 ADA result (negative, positive, or inconclusive) post-baseline.
Measured: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 20 months
Phase 1 and 2: Number of Participants With ADA to Cemiplimab
ADA responses were categorized as treatment-induced ADA and treatment boosted ADA. Pre-existing ADA was defined as ADA that were present in samples drawn during the pre-treatment period. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without pre-existing ADA. Treatment boosted ADA was defined as pre-existing ADAs with a significant increase in the ADA titer during the study compared to the Baseline titer.
Measured: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2017
- Study start21 Feb 2018
- Primary completion5 Apr 2023
- Study completion5 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03194867
- Sponsor's protocol ID
- TCD14906
- Other IDs
- 2017-001431-39, U1111-1189-4706, 2017
- Status last verified
- May 2024
- First submitted
- 19 Jun 2017
- Last updated
- 14 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics and Efficacy of Isatuximab in Combination With Cemiplimab in Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03194867
- Acronym / sponsor ID
- TCD14906
- Conditions
- Plasma Cell Myeloma
- Keywords
- Anti-CD38 monoclonal antibody
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 21 Feb 2018 (actual)
- Primary completion
- 5 Apr 2023 (actual)
- Study completion
- 5 Apr 2023 (actual)
- First posted
- 21 Jun 2017 (actual)
- Results
- Posted 14 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Isatuximab/cemiplimab (Regimen 1) | Experimental | Drug: Isatuximab SAR650984, Drug: Cemiplimab REGN2810Isatuximab 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. |
| Isatuximab/cemiplimab (Regimen 2) | Experimental | Drug: Isatuximab SAR650984, Drug: Cemiplimab REGN2810Isatuximab 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. |
| Isatuximab | Active comparator | Drug: Isatuximab SAR650984Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, as defined below:
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isatuximab SAR650984Also: SarclisaPharmaceutical form: solution for infusion Route of administration: intravenous | Drug | Isatuximab, Isatuximab/cemiplimab (Regimen 1), Isatuximab/cemiplimab (Regimen 2) |
| Cemiplimab REGN2810Pharmaceutical form: solution for infusion Route of administration: intravenous | Drug | Isatuximab/cemiplimab (Regimen 1), Isatuximab/cemiplimab (Regimen 2) |
Primary outcome
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1 Day 1 to Day 28
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.
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
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.
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
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.
15 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
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
Phase 1 and 2: AUC From Time 0 to Week 1 (AUC1week) 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
Phase 1 and 2: Number of Participants With Anti-Drug Antibodies (ADA) to Isatuximab
Time frame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 20 months
Phase 1 and 2: Number of Participants With ADA to Cemiplimab
Time frame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 20 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
30 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Isatuximab SAR650984 and Cemiplimab REGN2810 in people with Plasma Cell Myeloma, run by Sanofi at 30 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Spain, United States, France, Australia, Brazil and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1 Day 1 to Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2024.