Back to resultsIsatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
Primary Purpose
Plasma Cell Myeloma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Isatuximab SAR650984
Cemiplimab REGN2810
Sponsored by
About this trial
This is an interventional treatment trial for Plasma Cell Myeloma focused on measuring Anti-CD38 monoclonal antibody
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.
Sites / Locations
- University of Colorado-Site Number:8400001
- University of Kansas Medical Center-Site Number:8400003
- Memorial Sloan-Kettering Cancer Center-Site Number:8400002
- Fox Chase Cancer Center-Site Number:8400004
- Investigational Site Number :0360003
- Investigational Site Number :0360002
- Investigational Site Number :0360001
- Investigational Site Number :0760003
- Investigational Site Number :0760001
- Investigational Site Number :0760004
- Investigational Site Number :1240001
- Investigational Site Number :1240005
- Investigational Site Number :1240003
- Investigational Site Number :2030002
- Investigational Site Number :2030003
- Investigational Site Number :2030001
- Investigational Site Number :2500004
- Investigational Site Number :2500002
- Investigational Site Number :2500003
- Investigational Site Number :2500001
- Investigational Site Number :3000001
- Investigational Site Number :3480002
- Investigational Site Number :3800005
- Investigational Site Number :3800003
- Investigational Site Number :3800001
- Investigational Site Number :7240003
- Investigational Site Number :7240004
- Investigational Site Number :7240002
- Investigational Site Number :7240005
- Investigational Site Number :7240006
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Isatuximab/cemiplimab (Regimen 1)
Isatuximab/cemiplimab (Regimen 2)
Isatuximab
Arm 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.
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.
Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression.
Outcomes
Primary Outcome Measures
Dose Limiting Toxicities (DLTs)
DLTs are following AEs in Cycle 1 unless due to disease progression or an obviously unrelated cause: Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention; G 4 non-hematological AE; G ≥2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AE
Adverse events (AEs) and changes in laboratory tests and vital signs
Number of patients with AEs and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling
Overall Response Rate (ORR)
ORR is defined as the proportion of patients with complete response (CR) (including sCR [stringent complete response]), very good partial response (VGPR) and partial response (PR)
Secondary Outcome Measures
Clinical Benefit Rate (CBR)
CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimal response (MR)
Duration of Response (DOR)
DOR is defined as the time from the date of the first response (≥PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first
Time to Response (TTR)
TTR is defined as time from first study treatment administration to first response (≥PR) that is subsequently confirmed
Progression Free Survival (PFS)
PFS is defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause
Overall Survival (OS)
OS defined as the time from the first study treatment administration to death from any cause
Assessment of PK parameter: partial AUC
AUC is area under the drug concentration versus time curve
Assessment of PK parameter: Cmax
Cmax is maximum drug concentration observed
Antibodies to isatuximab
Levels of anti isatuximab antibodies in plasma samples will be determined
Antibodies to cemiplimab
Levels of anti cemiplimab antibodies in serum samples will be determined
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03194867
Brief Title
Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 18, 2023
Overall Recruitment Status
Completed
Study Start Date
January 25, 2018 (Actual)
Primary Completion Date
April 5, 2023 (Actual)
Study Completion Date
April 5, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasma Cell Myeloma
Keywords
Anti-CD38 monoclonal antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
109 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Isatuximab/cemiplimab (Regimen 1)
Arm Type
Experimental
Arm 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.
Arm Title
Isatuximab/cemiplimab (Regimen 2)
Arm Type
Experimental
Arm 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.
Arm Title
Isatuximab
Arm Type
Active Comparator
Arm Description
Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression.
Intervention Type
Drug
Intervention Name(s)
Isatuximab SAR650984
Other Intervention Name(s)
Sarclisa
Intervention Description
Pharmaceutical form: solution for infusion
Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
Cemiplimab REGN2810
Intervention Description
Pharmaceutical form: solution for infusion
Route of administration: intravenous
Primary Outcome Measure Information:
Title
Dose Limiting Toxicities (DLTs)
Description
DLTs are following AEs in Cycle 1 unless due to disease progression or an obviously unrelated cause: Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention; G 4 non-hematological AE; G ≥2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AE
Time Frame
Up to 4 weeks
Title
Adverse events (AEs) and changes in laboratory tests and vital signs
Description
Number of patients with AEs and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling
Time Frame
Up to 90 days following the last administration of study treatment for ongoing related AE, ongoing serious AE and new related AE until resolution or stabilization
Title
Overall Response Rate (ORR)
Description
ORR is defined as the proportion of patients with complete response (CR) (including sCR [stringent complete response]), very good partial response (VGPR) and partial response (PR)
Time Frame
Up to 6 months from last patient in (LPI) for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Secondary Outcome Measure Information:
Title
Clinical Benefit Rate (CBR)
Description
CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimal response (MR)
Time Frame
Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Title
Duration of Response (DOR)
Description
DOR is defined as the time from the date of the first response (≥PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first
Time Frame
Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Title
Time to Response (TTR)
Description
TTR is defined as time from first study treatment administration to first response (≥PR) that is subsequently confirmed
Time Frame
Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Title
Progression Free Survival (PFS)
Description
PFS is defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause
Time Frame
Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Title
Overall Survival (OS)
Description
OS defined as the time from the first study treatment administration to death from any cause
Time Frame
Up to 12 months from LPI for the final analysis
Title
Assessment of PK parameter: partial AUC
Description
AUC is area under the drug concentration versus time curve
Time Frame
Up to 4 weeks
Title
Assessment of PK parameter: Cmax
Description
Cmax is maximum drug concentration observed
Time Frame
Up to 4 weeks
Title
Antibodies to isatuximab
Description
Levels of anti isatuximab antibodies in plasma samples will be determined
Time Frame
Up to 12 months from LPI for the final analysis
Title
Antibodies to cemiplimab
Description
Levels of anti cemiplimab antibodies in serum samples will be determined
Time Frame
Up to 12 months from LPI for the final analysis
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
University of Colorado-Site Number:8400001
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
University of Kansas Medical Center-Site Number:8400003
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7321
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center-Site Number:8400002
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Fox Chase Cancer Center-Site Number:8400004
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Investigational Site Number :0360003
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
Facility Name
Investigational Site Number :0360002
City
Richmond
State/Province
Victoria
ZIP/Postal Code
3121
Country
Australia
Facility Name
Investigational Site Number :0360001
City
West Perth
State/Province
Western Australia
ZIP/Postal Code
6005
Country
Australia
Facility Name
Investigational Site Number :0760003
City
Goiania
State/Province
Goiás
ZIP/Postal Code
74605-020
Country
Brazil
Facility Name
Investigational Site Number :0760001
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90110-270
Country
Brazil
Facility Name
Investigational Site Number :0760004
City
Sao Paulo
State/Province
São Paulo
ZIP/Postal Code
01236030
Country
Brazil
Facility Name
Investigational Site Number :1240001
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Investigational Site Number :1240005
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4J 1C5
Country
Canada
Facility Name
Investigational Site Number :1240003
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Investigational Site Number :2030002
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
Investigational Site Number :2030003
City
Ostrava - Poruba
ZIP/Postal Code
70852
Country
Czechia
Facility Name
Investigational Site Number :2030001
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Investigational Site Number :2500004
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Investigational Site Number :2500002
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Investigational Site Number :2500003
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Investigational Site Number :2500001
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Investigational Site Number :3000001
City
Athens
ZIP/Postal Code
11528
Country
Greece
Facility Name
Investigational Site Number :3480002
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Investigational Site Number :3800005
City
Rozzano
State/Province
Milano
ZIP/Postal Code
20089
Country
Italy
Facility Name
Investigational Site Number :3800003
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Investigational Site Number :3800001
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Investigational Site Number :7240003
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08035
Country
Spain
Facility Name
Investigational Site Number :7240004
City
Badalona
State/Province
Catalunya [Cataluña]
ZIP/Postal Code
08916
Country
Spain
Facility Name
Investigational Site Number :7240002
City
Barcelona
State/Province
Catalunya [Cataluña]
ZIP/Postal Code
08036
Country
Spain
Facility Name
Investigational Site Number :7240005
City
Valencia
State/Province
Valenciana, Comunidad
ZIP/Postal Code
46017
Country
Spain
Facility Name
Investigational Site Number :7240006
City
Madrid
ZIP/Postal Code
28041
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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
Learn more about this trial
Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
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