Clinical Trials Register

Summary
EudraCT Number:	2019-004699-21
Sponsor's Protocol Code Number:	CP-MGAH22-06
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-21
Trial 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-004699-21

A.3

Full title of the trial

A Phase 2/3 Trial to Evaluate Margetuximab in Combination with INCMGA00012 and Chemotherapy or MGD013 and Chemotherapy in Patients with Metastatic or Locally Advanced, Treatment-naïve, HER2-Positive Gastric or Gastroesophageal Junction Cancer

Sperimentazione di fase II/III per valutare margetuximab in combinazione con INCMGA00012 e chemioterapia o MGD013 e chemioterapia in pazienti con tumore gastrico o della giunzione gastroesofagea HER2-positivo, naïve al trattamento, metastatico o localmente avanzato

A.3.1

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

Study of Margetuximab in Combination with INCMGA00012 and Chemotherapy or MGD013 and Chemotherapy in HER2-Positive Gastric or Gastroesophageal Junction Cancer

Studio su margetuximab in combinazione con INCMGA00012 e chemioterapia o MGD013 e chemioterapia nel tumore gastrico o della giunzione gastroesofagea HER2-positivo

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CP-MGAH22-06

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04082364

A.5.4

Other Identifiers

Name:

IND number

Number:

142220

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.4.1	Name of organisation providing support	Zai Lab (Shanghai) Co., Ltd. (MacroGenics collaborator)
B.4.2	Country	China
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	Clinical Project Management
B.5.3	Address:
B.5.3.1	Street Address	9704 Medical Center Drive
B.5.3.2	Town/ city	Rockville
B.5.3.3	Post code	MD 20850
B.5.3.4	Country	United States
B.5.6	E-mail	wortha@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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	5-fluorouracile
D.3.2	Product code	[na]
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUOROURACILE
D.3.9.1	CAS number	51-21-8
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB07721MIG
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	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	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	European Union
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	Trastuzumab
D.3.2	Product code	[na]
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	na
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.IMP: 3
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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Capecitabina
D.3.2	Product code	[na]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CAPECITABINA
D.3.9.1	CAS number	154361-50-9
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB12474MIG
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	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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: 4
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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Calcio folinato
D.3.2	Product code	[na]
D.3.4	Pharmaceutical form	Solution for injection
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	CALCIO FOLINATO
D.3.9.1	CAS number	1492-18-8
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB06052MIG
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	63
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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: 5
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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Oxaliplatino
D.3.2	Product code	[na]
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	OXALIPLATINO
D.3.9.1	CAS number	61825-94-3
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB09490MIG
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	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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: 6
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	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	Margetuximab
D.3.9.1	CAS number	1350624-75-7
D.3.9.2	Current sponsor code	MGAH22
D.3.9.3	Other descriptive name	MARGETUXIMAB
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: 7
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	INCMGA00012
D.3.2	Product code	[na]
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.3.9.1	CAS number	2079108-44-2
D.3.9.2	Current sponsor code	INCMGA00012
D.3.9.3	Other descriptive name	MGA012
D.3.9.4	EV Substance Code	SUB191459
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: 8
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	MGD013
D.3.2	Product code	[na]
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.3.9.2	Current sponsor code	MGD013
D.3.9.4	EV Substance Code	SUB195435
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	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, Treatment-naïve, HER2-Positive Gastric or Gastroesophageal Junction Cancer

Tumore gastrico o della giunzione gastroesofagea HER2-positivo, naïve al trattamento, metastatico o localmente avanzato

E.1.1.1

Medical condition in easily understood language

Gastric Cancer or Gastroesophageal Junction Cancer

Tumore gastrico o della giunzione gastroesofagea

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	23.0
E.1.2	Level	PT
E.1.2	Classification code	10066896
E.1.2	Term	HER2 positive gastric 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	PT
E.1.2	Classification code	10017758
E.1.2	Term	Gastric 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	10066354
E.1.2	Term	Adenocarcinoma of the gastroesophageal junction
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

Cohort A:
To evaluate the safety and tolerability of margetuximab + INCMGA00012 in patients with untreated locally advanced or metastatic GC or gastroesophageal junction (GEJ) cancer that is HER2 IHC 3+ and PD-L1+ by IHC staining.

To evaluate the ORR of margetuximab plus INCMGA00012 for non-MSI-H patients in the response evaluable population (REP) using independent and Investigator-assessed radiology reviews.

Cohort B, Part 1:
To select the best margetuximab, chemotherapy and CPI-containing combination regimen for further evaluation in Part 2, based on evaluation of safety and ORR in the primary response evaluable population (PREP) of patients with GC or GEJ cancer, irrespective of PD-L1 status.

Cohort B, Part 2:
To compare the OS of patients treated with the margetuximab, chemotherapy and CPI-containing arm selected from Cohort B Part 1 to that of patients treated with trastuzumab plus chemotherapy (control arm) in the primary efficacy population.

Coorte A:
Valutare la sicurezza e la tollerabilità di margetuximab + INCMGA00012 in pazienti con carcinoma gastrico (GC) o carcinoma della giunzione gastroesofagea (GGE) localmente avanzato o metastatico non trattato, che è positivo al fattore di crescita epidermico umano 2 (HER2) con immunoistochimica (IHC) 3+ e PD-L1+ mediante colorazione IHC.

Si prega di fare riferimento alla sinossi per i restanti

E.2.2

Secondary objectives of the trial

Cohort A:
To determine duration of response (DoR), disease control rate (DCR), progression-free survival (PFS) using independent and Investigator-assessed radiology review, and OS for non-MSI-H patients.

Cohort B, Part 1:
To evaluate PFS, OS, DoR, and DCR of each treatment arm.
To evaluate the ORR, DoR, DCR, PFS, and OS in the double-positive (HER2 3+ and PD-L1+) and non-MSI-H population in the margetuximab and chemotherapy arm

Cohort B Part 2:
To evaluate PFS, DoR, ORR and DCR of each treatment arm. To evaluate OS in the intent-to-treat (ITT), and non-PEP populations.
To evaluate the ORR, PFS, DoR, DCR and OS in the double-positive (HER2 3+ and PD-L1+) and non-MSI-H population in the margetuximab and CPI-containing arm.

-Please refer to protocol for further details.

Coorte A:
• Determinare la durata della risposta (DoR), il tasso di controllo della malattia (DCR), la sopravvivenza libera da progressione (PFS) mediante revisione radiologica indipendente e valutata dallo sperimentatore e la OS per i pazienti non-MSI-H.

Coorte B, Parte 1:
• Valutare PFS, OS, DoR e DCR di ciascun braccio di trattamento.
• Valutare ORR, DoR, DCR, PFS e OS nella popolazione doppio positiva (HER2 3+ e PD-L1+) e non-MSI-H nel braccio con margetuximab e chemioterapia

Coorte B, Parte 2:
• Valutare PFS, DoR, ORR e DCR di ciascun braccio di trattamento.
• Valutare l'OS nelle popolazioni intent-to-treat (ITT) e non-PEP.
• Valutare ORR, PFS, DoR, DCR, e OS nella popolazione doppio positiva (HER2 3+ e PD-L1+) e non-MSI-H nel braccio contenente margetuximab e CPI.

Si prega di fare riferimento alla sinossi per i restanti e al Protocollo per ulteriori dettagli

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma
- Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS > or = 1%), per central review

- Cohort B: HER2-positive (by IHC 3+ or IHC 2+ in combination with FISH+) by local review. PD -L1 status is not required for enrollment.

2. Availability of formalin-fixed, paraffin-embedded tumor specimen, unstained slides or contemporaneous biopsy for tumor target testing

3. Eastern Cooperative Oncology Group performance status of 0 or 1, verified within 3 days of Day 1

4. Life expectancy > or = 6 months

5. At least one radiographically measurable target lesion

6. Acceptable laboratory parameters and adequate organ function

1 Diagnosi istologicamente confermata di adenocarcinoma GC o della GGE HER2+ non trattato in precedenza, localmente avanzato, non resecabile o metastatico
- Coorte A: i pazienti saranno HER2+ (IHC 3+), PD-L1+ [punteggio positivo combinato (CPS > o =1%)] in base alla revisione centrale.

- Coorte B: HER2+ (IHC 3+, o IHC 2+ in combinazione con FISH+) in base alla revisione locale, indipendentemente dallo stato di PD-L1

2. Disponibilità di campioni di tumore fissati in formalina, inclusi in paraffina, vetrini non colorati o biopsia contemporanea per test sul tumore

3. Stato di validità del Gruppo cooperativo orientale di oncologia (ECOG) di 0 o 1, verificato entro 3 giorni dal Giorno 1

4. Aspettativa di vita > o = 6 mesi

5. Almeno una lesione target misurabile radiograficamente

6. Accettabili parametri di laboratorio e adeguata funzione d'organo

E.4

Principal exclusion criteria

1. Other malignancy that is progressing or required treatment within the past 5 years, with certain exceptions
-Patients with known MSI-H status

2. History of allogeneic stem cell or tissue/solid organ transplant

3. Central nervous system metastases

4. Clinically significant cardiovascular disease, gastrointestinal disorders, pulmonary compromise

5. Prior neoadjuvant or adjuvant treatment with immunotherapy

1. Altre neoplasie che stanno progredendo o hanno richiesto un trattamento negli ultimi 5 anni, con alcune eccezioni
- pazienti con elevata instabilità microsatellitare (MSI-H) nota

2. Storia di trapianto di cellule staminali allogeniche o di tessuto / organo solido

3. Metastasi del sistema nervoso centrale

4. Malattie cardiovascolari clinicamente significative, disturbi gastrointestinali, compromissione polmonare

5. Precedente trattamento neoadiuvante o adiuvante con immunoterapia

E.5 End points

E.5.1

Primary end point(s)

1) Incidence of Adverse Events of margetuximab plus INCMGA00012 as assessed by CTCAE
-Evaluation of adverse events and serious adverse events (Cohort A)

2) Objective response rate (ORR)
-Proportion of patients with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A and B)

3) Overall survival
-Time from randomization to death from any cause (Cohort B)

1) Incidenza degli eventi avversi di margetuximab più INCMGA00012 come valutato dai criteri terminologici comuni per gli eventi avversi (CTCAE)
- Valutazione degli eventi avversi e degli eventi avversi seri (Coorte A)

2) Tasso di risposta obiettiva (ORR)
- la proporzione di pazienti con la migliore risposta complessiva (CR) più risposta parziale (PR) secondo i criteri RECIST 1.1 (Coorte A e B)

3) Overall survival (OS)
- il tempo trascorso dal momento della randomizzazione al decesso per qualsiasi causa (Coorte B)

E.5.1.1

Timepoint(s) of evaluation of this end point

1) Time Frame: 6 month intervals
2) Time Frame: 3 years
3) Time Frame: Up to 3 years

1) Periodo di tempo: intervalli di 6 mesi
2) Periodo di tempo: 3 anni
3) Periodo di tempo: fino a 3 anni

E.5.2

Secondary end point(s)

1) Progression-free survival
-Time from start of study treatment to the first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurs first. (Cohorts A and B)

2) Duration of response
-Time from the date of initial response (CR or PR) to the date of first documented progression or death from any cause, whichever occurs first (Cohorts A and B)

3) Disease control rate
-Percentage of patients who experienced response of CR, PR or stable disease for at least 3 months from start of study treatment (Cohorts A and B)

4) Patient reported quality of life
-Quality of life as assessed using the Functional Assessment of Cancer Therapy - Gastric Questionnaire (FACT-Ga) (Cohort B) on a scale of 0 to 184. Lower scores correlate with worse quality of life and higher scores correlate with better quality of life.

1) Sopravvivenza libera da progressione
-il tempo dall'inizio del trattamento dello studio alla prima progressione della malattia documentata secondo i criteri RECIST v1.1 oppure il decesso per qualsiasi causa, a seconda di quale evento si verifichi prima. (Coorte A e B)

2) Durata della risposta
-il tempo dalla data della risposta iniziale (CR o PR) alla data della prima progressione documentata o decesso per qualsiasi causa, a seconda di quale evento si verifichi prima. (Coorte A e B)

3) Tasso di controllo della malattia
- la percentuale della REP che ha manifestato risposta di CR, PR o SD per almeno 3 mesi dall'inizio del trattamento dello studio. (Coorte A e B)

4) Qualità della vita riportata dal paziente
- Qualità della vita valutata utilizzando il Functional Assessment of Cancer Therapy
- Questionario gastrico (FACT-Ga) (Coorte B) su una scala da 0 a 184. I punteggi più bassi sono correlati ad una peggiore qualità della vita e i punteggi più alti sono correlati ad una migliore qualità della vita.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Time Frame: Up to 3 years

2) Time Frame: Up to 3 years

3) Time Frame: Up to 3 years

4) Time Frame: Up to 3 years

1) Periodo di tempo: fino a 3 anni
2) Periodo di tempo: fino a 3 anni
3) Periodo di tempo: fino a 3 anni
4) Periodo di tempo: fino a 3 anni

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)

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

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

China

Korea, Republic of

Singapore

Taiwan

United States

Germany

Italy

Netherlands

Poland

Spain

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 study is reached when the number of deaths required for final survival analysis for Cohort B is achieved and the study database is locked for the final survival analysis of Cohort B, which will be basis for the final clinical study report (CSR), or the closure of study by study Sponsor.

La fine dello studio è raggiunta quando viene raggiunto il numero di decessi richiesti per l'analisi di sopravvivenza finale per la Coorte B e la banca dati dello studio viene bloccata per l'analisi di sopravvivenza finale della Coorte B, che costituirà la base per la relazione finale dello studio clinico (CSR) o la chiusura dello studio da parte dello sponsor dello studio.

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:

460

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

400

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

240

F.4.2.2

In the whole clinical trial

860

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

2020-09-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-16

P. End of Trial
P.	End of Trial Status	Completed

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