Clinical Trials Register

Summary
EudraCT Number:	2015-000380-13
Sponsor's Protocol Code Number:	CP-MGAH22-04
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-13
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-000380-13

A.3

Full title of the trial

A Phase 3, Randomized Study of Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of Patients with HER2+ Metastatic Breast Cancer Who Have Received Two Prior Anti-HER2 Therapies and Require Systemic Treatment

Studio di fase 3 randomizzato su margetuximab + chemioterapia vs. trastuzumab + chemioterapia nel trattamento di pazienti con carcinoma mammario HER2+ metastatico precedentemente trattati con due terapie anti-HER2 che necessitano di terapia sistemica.

A.3.1

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

A Phase 3 Study of Margetuximab Plus Chemotherapy vs Trastuzumab plus
Chemotherapy in the Treatment of Patients with HER2+ Metastatic Breast
Cancer (SOPHIA).

Studio di fase 3 su margetuximab + chemioterapia vs. trastuzumab + chemioterapia nel trattamento di pazienti con tumore al seno HER2+ metastatico (SOPHIA).

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CP-MGAH22-04

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	MACROGENICS, INC.
B.1.3.4	Country	United States
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	MacroGenics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MacroGenics, Inc.
B.5.2	Functional name of contact point	Seila Liv -Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	One Corporate Drive
B.5.3.2	Town/ city	South San Francisco California
B.5.3.3	Post code	94080
B.5.3.4	Country	United States
B.5.4	Telephone number	0016506242662
B.5.5	Fax number	0016506242693
B.5.6	E-mail	livs@macrogenics.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	Margetuximab
D.3.2	Product code	MGAH22
D.3.4	Pharmaceutical form	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	Margetuximab
D.3.9.1	CAS number	1350624-75-7
D.3.9.2	Current sponsor code	MGAH22
D.3.9.4	EV Substance Code	SUB175279
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	25
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Comparator
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	Yes
D.2.1.1.1	Trade name	Herceptin
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	Pharmaceutical form	Powder 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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB12612MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Metastatic or Locally Advanced HER2-positive Breast Cancer

Carcinoma mammario HER2-positivo metastatico o localmente avanzato

E.1.1.1

Medical condition in easily understood language

Advanced Breast Cancer

Carcinoma mammario avanzato

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	LLT
E.1.2	Classification code	10027475
E.1.2	Term	Metastatic breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	PT
E.1.2	Classification code	10065430
E.1.2	Term	HER2 positive breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10072740
E.1.2	Term	Locally advanced breast cancer
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

The primary objective of this study is to evaluate the efficacy, as measured by progression-free survival (PFS) assessed by independent review and overall survival (OS), of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with advanced HER2+ breast cancer who have received prior treatment with trastuzumab, pertuzumab, and do-trastuzumab emtansine in the neoadjuvant, adjuvant, or metastatic setting, and who have received at least one, and no more than two, lines of therapy in the metastatic setting.

L¿obiettivo primario di questo studio ¿ valutare l¿efficacia misurata in termini di sopravvivenza libera da progressione (PFS), determinata tramite valutazione indipendente, e la sopravvivenza generale (OS) di margetuximab pi¿ chemioterapia rispetto a trastuzumab pi¿ chemioterapia in pazienti con carcinoma mammario HER2+ in stadio avanzato trattati in precedenza con trastuzumab, pertuzumab e ado-trastuzumab emtansina nel contesto neoadiuvante, adiuvante o metastatico e trattati con almeno una, e non pi¿ di due, linee di terapia nel contesto metastatico.

E.2.2

Secondary objectives of the trial

¿To evaluate PFS, as assessed by study investigators, of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in these patients.
¿To evaluate by independent review the objective response rate (ORR) of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy
in these patients.

¿valutare la PFS, come determinata dagli sperimentatori, di margetuximab pi¿ chemioterapia vs. trastuzumab pi¿ chemioterapia in questi pazienti;
¿valutare il tasso di risposta obiettiva (ORR), come emerso da valutazione indipendente, di margetuximab pi¿ chemioterapia vs. trastuzumab pi¿ chemioterapia in questi pazienti.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patients = 18 years of age.
2. Have histologically-proven metastatic or locally-advanced relapsed/refractory HER2+ breast cancer. Tumors may be estrogen receptor (ER)/progesterone receptor (PR) positive or negative.
3. Have received prior treatment with pertuzumab, trastuzumab, and ado-trastuzumab emtansine in the neoadjuvant, adjuvant, or metastatic setting. Prior radiotherapy and hormonal therapies are allowed.
4. Have received treatment for at least one, and no more than two, lines of therapy in the metastatic setting. Prior neo-adjuvant or adjuvant therapy that resulted in relapse within 6 months of completion of
therapy will be considered a line of treatment for metastatic disease.
Eligible patients must have progressed on or following, the most recent line of therapy.
5. Resolution of all chemotherapy or radiation-related toxicities to =Grade 1 (with exception of = Grade 2 alopecia, stable sensory neuropathy, or stable electrolyte disturbances that are managed by
supplementation).
6. Have life expectancy = 12 weeks.
7. Have acceptable laboratory parameters.
8. Female patients of childbearing potential must have negative pregnancy test. All subjects should practice effective contraception.

1.Pazienti di età =18 anni. Possono essere di sesso sia maschile sia femminile.
2.Carcinoma mammario HER2+ refrattario/recidivato, in stadio metastatico o localmente avanzato, istologicamente documentato. I tumori possono essere positivi o negativi al recettore estrogenico (ER)/recettore progestinico (PR).
3.Precedente trattamento con pertuzumab, trastuzumab e ado-trastuzumab emtansina nel contesto neoadiuvante, adiuvante o metastatico. Sono consentite precedenti radioterapie e terapie ormonali.
4.Trattamento con almeno una, e non più di due, linee di terapia nel contesto metastatico. Una precedente terapia neo-adiuvante o adiuvante con conseguente recidiva entro 6 mesi dalla sua conclusione sarà considerata una linea di terapia per il trattamento della malattia metastatica. I pazienti idonei devono aver mostrato segni di progressione durante o dopo la linea di terapia più recente.
5.Risoluzione di tutte le tossicità correlate a chemioterapia o radioterapia al grado =1 (ad eccezione dell’alopecia di grado =2, della neuropatia sensoriale stabile o di alterazioni stabili dell’equilibrio elettrolitico gestite con supplementazione)
6.Aspettativa di vita =12 settimane
7.Parametri di laboratorio accettabili.
8.Le pazienti in età fertile devono presentare risultato negativo a un test di gravidanza. Tutti i soggetti devono praticare una contraccezione efficace.

E.4

Principal exclusion criteria

1. Patients with known, untreated brain metastasis. Patients with signs or symptoms of brain metastasis must have a CT or MRI performed
within 4 weeks prior to randomization to specifically exclude the presence of radiographically-detectable brain metastases.
2. History of uncontrolled seizures.
3. History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.
4. History of clinically significant cardiovascular disease.
5. Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
6. Any condition that would be a contraindication to receiving trastuzumab as described in the approved local label or a condition that would prevent treatment with the physician's choice of chemotherapies.

1.Pazienti con metastasi cerebrali non trattate note. I pazienti con segni o sintomi di metastasi cerebrali devono essere sottoposti a TC o RMI nelle 4 settimane precedenti la randomizzazione per escludere in modo specifico la presenza di metastasi cerebrali rilevabili radiograficamente.
2.Storia di convulsioni non controllate.
3.Storia di trapianto allogenico di midollo osseo, cellule staminali o organo solido.
4.Storia di malattia cardiovascolare clinicamente significativa.
5.Compromissione polmonare clinicamente significativa, inclusa la necessità di ossigenoterapia per mantenere un’adeguata ossigenazione.
6.Qualsiasi affezione che potrebbe costituire una controindicazione a trastuzumab in base alle indicazioni prescrittive locali approvate o affezione che potrebbe impedire il trattamento con la chemioterapia scelta dal medico.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival as determined by independent radiological review.
Overall survival defined as the number of days from randomization to the date of death (from any cause).

Sopravvivenza libera da progressione come valutata dalla revisione radiologica indipendente.
La sopravvivenza generale sarà calcolata come numero di giorni intercorsi dalla data di randomizzazione fino al decesso per qualsiasi causa.

E.5.1.1

Timepoint(s) of evaluation of this end point

For PFS: 24 months from the start of the study
For OS: 36 months from the start of the study

Per PFS: 24 mesi dall'inizio dello studio
Per OS: 36 mesi dall'inizio dello studio

E.5.2

Secondary end point(s)

Overall response rate (ORR) as determined by independent radiological review
PFS as determined by study investigators

Il tasso di risposta complessivo (ORR) come valutato dalla revisione radiologica indipendente
PFS come valutata dagli sperimentatori.

E.5.2.1

Timepoint(s) of evaluation of this end point

For ORR: 36 months from the start of the study
For PFS: 24 months from the start of the study

Per ORR: 36 mesi dall'inizio dello studio
Per PFS: 24 mesi dall'inizio dello studio

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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)

Yes

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

115

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

Information not present in EudraCT

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

Canada

Israel

United States

Austria

Belgium

Czechia

Denmark

Finland

France

Germany

Italy

Netherlands

Portugal

Spain

Switzerland

United Kingdom

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

The end of this study is defined as when the last patient visit occurs or one year after the final survival analysis, whichever occurs first.

La conclusione della sperimentazione ¿ definita come l'ultima visita dell'ultimo paziente o un anno dopo l¿analisi finale dei dati sulla sopravvivenza, qualunque avvenga prima.

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

130

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

297

F.4.2.2

In the whole clinical trial

530

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

Nessuno

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

2015-10-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-09

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials