Clinical Trials Register

Summary
EudraCT Number:	2017-001431-39
Sponsor's Protocol Code Number:	TCD14906
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-06-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2017-001431-39

A.3

Full title of the trial

A Phase 1/2 study to evaluate safety, pharmacokinetics and efficacy of isatuximab in combination with REGN2810 in patients with relapsed/refractory multiple myeloma

I/II. fázisú vizsgálat a REGN2810 készítménnyel kombinációban alkalmazott isatuximab biztonságosságának, farmakokinetikájának és hatásosságának értékelésére relabáló/kezelésre nem reagáló myeloma multiplexben szenvedő betegeknél

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Isatuximab in Combination with REGN2810 in RRMM Patients

A REGN2810 készítménnyel kombinációban alkalmazott isatuximab RRMM betegeknél

A.4.1

Sponsor's protocol code number

TCD14906

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1189-4706

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi-aventis recherche & developpement
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi-aventis recherche & developpement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi-Aventis Zrt.
B.5.2	Functional name of contact point	NA
B.5.3	Address:
B.5.3.1	Street Address	Tó u . 1-5.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1045
B.5.3.4	Country	Hungary
B.5.6	E-mail	kapcsolat@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/14/1268
D.3 Description of the IMP
D.3.1	Product name	isatuximab
D.3.2	Product code	SAR650984
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	isatuximab
D.3.9.2	Current sponsor code	SAR650984
D.3.9.3	Other descriptive name	SAR650984
D.3.9.4	EV Substance Code	SUB119676
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	REGN2810
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.2	Current sponsor code	REGN2810
D.3.9.3	Other descriptive name	Anti-PD-1 monoclonal antibody
D.3.9.4	EV Substance Code	SUB179369
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cancer

Daganat

E.1.1.1

Medical condition in easily understood language

Cancer

Daganat

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)

E.1.3

Condition being studied is a rare disease

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 REGN2810 in patients with relapse/refractory multiple myeloma.

-To evaluate the overall response rate of the combination of Isatuximab and REGN2810 in patients
with RRMM.

- Az isatuximab és a REGN2810 kombinációja biztonságosságának és tolerálhatóságának meghatározása relabáló/kezelésre nem reagáló myeloma multiplexben szenvedő (RRMM) betegeknél.

- Az isatuximab és a REGN2810 kombináció összesített válaszarányának meghatározássa RRMM betegek körében.

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 REGN2810 when given in combination.

-To assess the immunogenicity of isatuximab and REGN2810

- A következő hatásossági mérőszámok meghatározása: a klinikai haszon aránya (CBR), a válasz időtartama (DOR), a válaszig eltelt idő (TTR), progressziómentes túlélés (PFS) és teljes túlélés (OS).

- A kombinációban alkalmazott isatuximab és REGN2810 farmakokinetikai profiljának megállapítása.

- A kombinációban alkalmazott isatuximab és REGN2810 immunogenitásának megállapítása.

E.2.3

Trial contains a sub-study

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)
OR
- Patients whose disease is double refractory to an IMID and a PI (disease progression has occurred while on or within 60 days from end of the treatment).

- Patient must have achieved MR or better with any anti-myeloma therapy (ie, primary refractory disease is not eligible).

- Patients must have a disease that is refractory to the most recent prior line therapy (disease progression has occurred while on treatment or within 60 days from end of the treatment).

-A betegnél ismerten myeloma multiplexet diagnosztizáltak, a mérhető betegség bizonyítékával, amelynek meghatározása:
Szérum M-protein ≥1 g/dl (≥0,5 g/dl IgA betegségben),
ÉS/VAGY
Vizelet M-protein ≥200 mg/24 h,
VAGY
Ha nincs mérhető M-protein, a szérum immunglobulin szabad könnyű lánc ≥10 mg/dl, és rendellenes szérum kappa-lambda immunglobulin könnyűlánc-arány (<0,26 vagy >1,65)

- A beteget korábban immunmódosító szerrel (IMiD) (a kezelés ≥2 ciklusig vagy ≥2 hónapig tartott) és proteaszóma-inhibitorral (PI) (a kezelés ≥2 ciklusig vagy ≥2 hónapig tartott) kezelték,

- A beteg VAGY legalább 3 korábbi kezelést kapott (megjegyzés: az indukciós terápia és őssejt-transzplantáció ± fenntartás egy kezelésnek számít)
VAGY
A betegség kétszeresen nem reagáló immunmódosító szerre és egy proteaszóma-inhibitorra (a legutóbbi kezelés során vagy a befejezését követő 60 napon belül rosszabbodott a betegség).

- A betegnek minimális vagy jobb választ kellett elérnie bármelyik myelomaellenes kezelés során (vagyis a primer nem reagáló betegséggel érintettek nem választhatók be).

- A csak refrakter betegségben szenvedő betegek esetében, a betegség nem reagál a legutóbb alkalmazott kezelésre (a legutóbbi kezelés során vagy a befejezését követő 60 napon belül rosszabbodott a betegség).

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.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2.
- Poor bone marrow reserve.
- Poor organ function.

- A beteg korábbi expozíciója isatuximabra, vagy részt vett az isatuximab klinikai vizsgálataiban,
- A beteg korábbi expozíciója PD-1/PD-L1 útvonalat gátló bármely (engedélyezett vagy vizsgálati) hatóanyagra
- Egyéb immunrendszeri betegségre/állapotra utaló bizonyíték
- Szteroidkezelést szükségessé tevő nem fertőzéses eredetű pneumonia a kórelőzményben vagy fennálló pneumonia; mellkasi besugárzás a kórelőzményben
- A beteg élővírus-vakcinát kapott a kezelés tervezett kezdete előtti 30 napon belül. Az élő vírust nem tartalmazó szezonális influenza-vakcinák megengedettek.
- Allogén hemopoetikus őssejt- (HSC-) átültetést végeztek;
- Az Eastern Cooperative Oncology Group (ECOG) teljesítménystátusz (PS) >2
- Elégtelen csontvelő funkció
- Elégtelen szervműködés

E.5 End points

E.5.1

Primary end point(s)

1 - Dose Limiting Toxicities (DLTs)
DLTs are treatment-related adverse reactions in Cycle 1. Hematological DLT – 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. Non-hematological DLT - G 4 nonhematological 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. Other dose-limiting AE.

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)

E.5.1.1

Timepoint(s) of evaluation of this end point

1 - Up to 4 weeks
2 - Up to 30 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

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 REGN2810
Levels of anti REGN2810 antibodies in serum samples will be determined

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised