Clinical Trials Register

Summary
EudraCT Number:	2018-002442-37
Sponsor's Protocol Code Number:	ACT15320
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-11-09
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

Portugal - INFARMED

A.2

EudraCT number

2018-002442-37

A.3

Full title of the trial

A Phase 1/2 open-label, multi-center, safety, preliminary efficacy and pharmacokinetic (PK) study of isatuximab in combination with other anti-cancer therapies in participants with lymphoma

A.3.1

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

A Study of Isatuximab-based Therapy in Participants with Lymphoma

A.4.1

Sponsor's protocol code number

ACT15320

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1211-9010

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, Produtos Farmacêuticos Lda
B.5.2	Functional name of contact point	Higor Faria
B.5.3	Address:
B.5.3.1	Street Address	Empreendimento Lagoas Park, Edifcio 7 Piso 3
B.5.3.2	Town/ city	Porto Salvo
B.5.3.3	Post code	2740-244
B.5.3.4	Country	Portugal
B.5.4	Telephone number	+351932984595
B.5.6	E-mail	higor.pereiradefaria@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	No
D.2.5.1	Orphan drug designation number
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.3.9.4	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.3.1	Product name	cemiplimab
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	cemiplimab
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

Lymphoma

E.1.1.1

Medical condition in easily understood language

Lymphoma

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	10025310
E.1.2	Term	Lymphoma
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

Phase 1
-To characterize the safety and tolerability of isatuximab in combination with cemiplimab in participants with relapsed and refractory classic Hodgkin’s lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma (PTCL), and to confirm the recommended Phase 2 dose (RP2D).
Phase 2
- Cohort A1 (anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] naive cHL): To assess the complete remission (CR) rate of isatuximab in combination with cemiplimab.
- Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): To assess the objective response rate (ORR) of isatuximab in combination with cemiplimab.

E.2.2

Secondary objectives of the trial

- To evaluate the safety of the RP2D of the combination of isatuximab with cemiplimab.
- To evaluate the safety of the combination of isatuximab with cemiplimab and radiotherapy in patients with cHL.
- To evaluate the immunogenicity of isatuximab and cemiplimab when given in combination.
- To characterize the pharmacokinetic (PK) profile of isatuximab and cemiplimab when given in combination.
-To assess overall efficacy of isatuximab in combination with cemiplimab and isatuximab in combination with cemiplimab and radiotherapy.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participants must be ≥ 12 years of age inclusive, at the time of signing the informed consent
- Disease location amenable to tumor biopsy at baseline
- Measurable disease
- For Cohort A1 (classic Hodgkin's lymphoma [cHL] anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] inhibitor naïve): Histologically confirmed advanced cHL that has relapsed or progressed after at least 3 lines of systemic therapy that may include autologous hematopoietic stem cell transplant (auto-HSCT) or auto-HSCT and brentuximab vedontin (BV)
-Cohort A2: classic Hodgkin's lymphoma with documentation of benefit but subsequent progression during or after the prior anti-PD1/PD-L1 containing regimen. Progression has to occur within 6 months from last dose of the prior anti-PD1/PD-L1 containing regimen
- For Cohort B (diffuse large B-cell lymphoma [DLBCL]):Histologically confirmed advanced DLBCL that has relapsed or progressed after 2 lines of systemic therapy including auto-HSCT or 2 lines of systemic therapy for participants who are not eligible for auto-HSCT
- For Cohort C (peripheral T-cell lymphoma [PTCL]): Histologically confirmed advanced PTCL that has relapsed or progressed after either first-line chemotherapy and auto-HSCT as consolidation of first remission or first-line chemotherapy if participants are ineligible for auto-HSCT
- Body weight of > 45 kg for patients with age <18 years

E.4

Principal exclusion criteria

-Prior exposure to agent that blocks CD38
- For patients with cHL (PD-1/PD-L1 naïve), DLBCL or PTCL prior exposure to any agent (approved or investigational) that blocks the PD-1/PD-L1, PD-L2, CD137, CTLA-4 or LAG-3
- Evidence of other immune related disease /conditions
- Has received a live-virus vaccination within 28 days of planned treatment start; seasonal flu vaccines that do not contain live virus are permitted
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2
- Poor bone marrow reserve
- Poor organ function

E.5 End points

E.5.1

Primary end point(s)

Phase 1
1) Dose limiting toxicities (DLTs): DLTs as observed during DLT-observation period
2) Recommended Phase 2 dose (RP2D): Dose selected for the Phase 2 portion
Phase 2
3) Cohort A1 (anti-PD-1/PD-L1 naive cHL): Complete Remission Rate: The proportion of participants who have a Complete Remission as a best overall response during the isatuximab + cemiplimab therapy period using the Lugano response criteria 2014
4) Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): Response Rate : The proportion of participants who have a Complete Response or Partial Response as a best overall response during isatuximab + cemiplimab therapy period using the Lugano response criteria 2014

E.5.1.1

Timepoint(s) of evaluation of this end point

1) and 2) 1st Cycle - 28 days
3) and 4) Up to 24 weeks after last patient treated in a given cohort

E.5.2

Secondary end point(s)

1) Adverse Events (AEs)/Serious Adverse Events (SAEs) for isatuximab + cemiplimab: Number of patients with AEs/SAEs
2) Adverse Events/Serious Adverse Events for isatuximab + cemiplimab + radiotherapy: Number of patients with AEs/SAEs in cohorts A1 and A2
3) Immunogenicity: Anti-drug antibody (ADA) levels against isatuximab and against cemiplimab
4) Pharmacokinetic evaluation: Pharmacokinetic evaluation using non-compartmental analysis for both compounds using serum concentrations for cemiplimab and plasma concentrations for isatuximab
5) Tumor burden change: The best percent-change from baseline
6) Disease control rate: The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
7) Duration of response: The time from the date of the first response (PR or CR in radiographic objective response) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first.
8) Progression free survival: The time from the first study treatment administration to the date of first documentation of progressive disease or death, whichever comes first.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) to 4) Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration)
5) to 8) Up to 24 weeks after last patient treated in a given cohort

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

Yes

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

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Korea, Republic of

Taiwan

France

Netherlands

Spain

Italy

Portugal

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

105

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

145

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-02-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-02-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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