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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03194867




Registration number
NCT03194867
Ethics application status
Date submitted
19/06/2017
Date registered
21/06/2017
Date last updated
4/06/2020

Titles & IDs
Public title
Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
Scientific 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
Secondary ID [1] 0 0
2017-001431-39
Secondary ID [2] 0 0
TCD14906
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Plasma Cell Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Isatuximab SAR650984
Treatment: Drugs - Cemiplimab REGN2810

Experimental: Isatuximab/cemiplimab (Regimen 1) - 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.

Experimental: Isatuximab/cemiplimab (Regimen 2) - 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.

Active Comparator: Isatuximab - Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression.


Treatment: Drugs: Isatuximab SAR650984
Pharmaceutical form: solution for infusion
Route of administration: intravenous

Treatment: Drugs: Cemiplimab REGN2810
Pharmaceutical form: solution for infusion
Route of administration: intravenous

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to 4 weeks
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
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)
Timepoint [3] 0 0
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 [1] 0 0
Clinical Benefit Rate (CBR) - CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimal response (MR)
Timepoint [1] 0 0
Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Secondary outcome [3] 0 0
Time to Response (TTR) - TTR is defined as time from first study treatment administration to first response (=PR) that is subsequently confirmed
Timepoint [3] 0 0
Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis
Secondary outcome [5] 0 0
Overall Survival (OS) - OS defined as the time from the first study treatment administration to death from any cause
Timepoint [5] 0 0
Up to 12 months from LPI for the final analysis
Secondary outcome [6] 0 0
Assessment of PK parameter: partial AUC - AUC is area under the drug concentration versus time curve
Timepoint [6] 0 0
Up to 4 weeks
Secondary outcome [7] 0 0
Assessment of PK parameter: Cmax - Cmax is maximum drug concentration observed
Timepoint [7] 0 0
Up to 4 weeks
Secondary outcome [8] 0 0
Antibodies to isatuximab - Levels of anti isatuximab antibodies in plasma samples will be determined
Timepoint [8] 0 0
Up to 12 months from LPI for the final analysis
Secondary outcome [9] 0 0
Antibodies to cemiplimab - Levels of anti cemiplimab antibodies in serum samples will be determined
Timepoint [9] 0 0
Up to 12 months from LPI for the final analysis

Eligibility
Key inclusion 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).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360002 - Richmond
Recruitment hospital [2] 0 0
Investigational Site Number 0360001 - West Perth
Recruitment hospital [3] 0 0
Investigational Site Number 0360003 - Wollongong
Recruitment postcode(s) [1] 0 0
3121 - Richmond
Recruitment postcode(s) [2] 0 0
6005 - West Perth
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
Brazil
State/province [5] 0 0
Goiania
Country [6] 0 0
Brazil
State/province [6] 0 0
Porto Alegre
Country [7] 0 0
Brazil
State/province [7] 0 0
São Paulo
Country [8] 0 0
Canada
State/province [8] 0 0
Montreal
Country [9] 0 0
Canada
State/province [9] 0 0
Sherbrooke
Country [10] 0 0
Czechia
State/province [10] 0 0
Brno
Country [11] 0 0
Czechia
State/province [11] 0 0
Ostrava - Poruba
Country [12] 0 0
Czechia
State/province [12] 0 0
Praha 2
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Nantes Cedex 01
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
France
State/province [16] 0 0
Pierre Benite
Country [17] 0 0
France
State/province [17] 0 0
Villejuif Cedex
Country [18] 0 0
Greece
State/province [18] 0 0
Athens
Country [19] 0 0
Hungary
State/province [19] 0 0
Budapest
Country [20] 0 0
Italy
State/province [20] 0 0
Bologna
Country [21] 0 0
Italy
State/province [21] 0 0
Brescia
Country [22] 0 0
Italy
State/province [22] 0 0
Rozzano
Country [23] 0 0
Italy
State/province [23] 0 0
Torino
Country [24] 0 0
Spain
State/province [24] 0 0
Badalona
Country [25] 0 0
Spain
State/province [25] 0 0
Barcelona
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid
Country [27] 0 0
Spain
State/province [27] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03194867
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications