E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10035226 |
E.1.2 | Term | Plasma cell myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
-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. |
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E.2.2 | Secondary objectives of the trial |
-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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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 IMiD (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (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). |
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E.4 | Principal exclusion criteria |
- Prior exposure to isatuximab or participated clinical studies with isatuximab.
- Prior exposure to any agent (approved or investigational) that blocks the 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1 - 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/AEs
2 - 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
3 - 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) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 - Up to 4 weeks
2 - 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
3 - Up to 6 months from last patient in for primary efficacy analysis, and up to 12 months from last patient in (LPI) for the final analysis |
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E.5.2 | Secondary end point(s) |
1 - Clinical Benefit Rate (CBR)
CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimalresponse (MR)
2 - 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
3 - Time to Response (TTR)
TTR is defined as time from first study treatment administration to first response (≥PR) that is subsequently confirmed
4 - 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
5 - Overall Survival (OS)
OS defined as the time from the first study treatment administration to death from any cause
6 - Assessment of PK parameter: partial AUC
AUC is area under the drug concentration versus time curve
7 - Assessment of PK parameter: Cmax
Cmax is maximum drug concentration observed
8 - Antibodies to isatuximab
Levels of anti isatuximab antibodies in plasma samples will be determined
9 - Antibodies to cemiplimab
Levels of anti cemiplimab antibodies in serum samples will be determined |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 to 4: Up to 6 months from last patient in for primary efficacy analysis, and up to 12 months from LPI for the final analysis
5: Up to 12 months from LPI for the final analysis
6 and 7: Up to 4 weeks
8 and 9: Up to 12 months from LPI for the final analysis |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
Czech Republic |
France |
Greece |
Hungary |
Italy |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 13 |