Clinical Trials Register

Summary
EudraCT Number:	2021-000296-36
Sponsor's Protocol Code Number:	ZWI-ZW25-301
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-08-26
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

Spain - AEMPS

A.2

EudraCT number

2021-000296-36

A.3

Full title of the trial

A Randomized, Multicenter, Phase 3 Study of Zanidatamab in Combination with Chemotherapy with or without Tislelizumab in Subjects with HER2-positive Unresectable Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma (GEA)

Estudio de fase III, multicéntrico y aleatorizado de zanidatamab en combinación con quimioterapia, con o sin tislelizumab, en sujetos con adenocarcinoma gastroesofágico (AGE) irresecable, localmente avanzado o metastásico, con HER-2 positivo

A.3.1

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

A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers

Estudio de Zanidatamab en combinación con quimioterapia, con o sin Tislelizumab, en pacientes con cancer gástrico y esofágico avanzado o metastásico, con HER-2 positivo

A.3.2

Name or abbreviated title of the trial where available

HERIZON-GEA-01

A.4.1

Sponsor's protocol code number

ZWI-ZW25-301

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	Zymeworks Inc.
B.1.3.4	Country	Canada
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	Zymeworks Inc.
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PPD
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	c/Titan , 15 6th Floor
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28045
B.5.3.4	Country	Spain
B.5.4	Telephone number	34900834223
B.5.5	Fax number	NA
B.5.6	E-mail	RegistroEspanolDeEstudiosClinicos@druginfo.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/3/20/2353
D.3 Description of the IMP
D.3.1	Product name	Zanidatamab
D.3.2	Product code	ZW25
D.3.4	Pharmaceutical form	Powder for 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	Zanidatamab
D.3.9.1	CAS number	2169946-15-8
D.3.9.2	Current sponsor code	ZW25
D.3.9.3	Other descriptive name	A bispecific antibody recognizing two non-overlapping epitopes of the extracellular domain of the human HER2 antigen
D.3.9.4	EV Substance Code	SUB203836
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	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	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/3/20/2353
D.3 Description of the IMP
D.3.1	Product name	Zanidatamab
D.3.2	Product code	ZW25
D.3.4	Pharmaceutical form	Powder for 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	Zanidatamab
D.3.9.1	CAS number	2169946-15-8
D.3.9.2	Current sponsor code	ZW25
D.3.9.3	Other descriptive name	A bispecific antibody recognizing two non-overlapping epitopes of the extracellular domain of the human HER2 antigen
D.3.9.4	EV Substance Code	SUB203836
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	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: 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.2.1.1.1	Trade name	Tislelizumab
D.2.1.1.2	Name of the Marketing Authorisation holder	BeiGene
D.2.1.2	Country which granted the Marketing Authorisation	China
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	BGB-A317
D.3.2	Product code	BGB-A317
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	Tislelizumab
D.3.9.1	CAS number	1858168-59-8
D.3.9.2	Current sponsor code	BGB-A317
D.3.9.3	Other descriptive name	BGB-A317
D.3.9.4	EV Substance Code	SUB189550
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	10
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	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	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 GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Herceptin
D.3.4	Pharmaceutical form	Powder for 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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
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	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	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	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 GmBH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Herceptin
D.3.4	Pharmaceutical form	Powder for 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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
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	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	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	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 Pharma (Schweiz) AG, Basel
D.2.1.2	Country which granted the Marketing Authorisation	Switzerland
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	Herceptin
D.3.4	Pharmaceutical form	Powder for 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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
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	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	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: 7
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 Pharma (Schweiz) AG, Basel
D.2.1.2	Country which granted the Marketing Authorisation	Switzerland
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	Herceptin
D.3.4	Pharmaceutical form	Powder for 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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
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	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	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: 8
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 Pharma (Schweiz) AG, Basel
D.2.1.2	Country which granted the Marketing Authorisation	Switzerland
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	Herceptin
D.3.4	Pharmaceutical form	Powder for 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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
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	440
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	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: 9
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 Pharma (Schweiz) AG, Basel
D.2.1.2	Country which granted the Marketing Authorisation	Switzerland
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	Herceptin
D.3.4	Pharmaceutical form	Powder for 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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
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	440
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	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.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

Gastroesophageal Adenocarcinoma (GEA)

Adenocarcinoma gastroesofágico (AGE)

E.1.1.1

Medical condition in easily understood language

Gastroesophageal Adenocarcinoma (GEA)

Adenocarcinoma gastroesofágico (AGE)

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	22.0
E.1.2	Level	LLT
E.1.2	Classification code	10082464
E.1.2	Term	Advanced gastric carcinoma
E.1.2	System Organ Class	100000004864

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	10055458
E.1.2	Term	Esophageal adenocarcinoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

●To compare the efficacy of zanidatamab in combination with chemotherapy or in combination with chemotherapy and tislelizumab to the efficacy of trastuzumab in combination with chemotherapy in subjects with unresectable locally advanced, recurrent or metastatic HER2 positive GEA

Comparar la eficacia de zanidatamab en combinación con quimioterapia o en combinación con quimioterapia y tislelizumab con la eficacia de
trastuzumab en combinación con quimioterapia en sujetos con AGE positivo para HER2 localmente avanzado, recurrente o metastásico irresecable.

E.2.2

Secondary objectives of the trial

●To further compare the efficacy of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab to chemotherapy with trastuzumab
●To evaluate the safety and tolerability of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab
●To evaluate the effect of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab on health-related quality of life (HRQoL)
●To evaluate the pharmacokinetics (PK) of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab
●To evaluate the PK of tislelizumab in combination with chemotherapy and zanidatamab
●To evaluate the immunogenicity of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab
●To evaluate the immunogenicity of tislelizumab in combination with chemotherapy and zanidatamab

- Comparar mejor la eficacia de zanidatamab en combinación con quimioterapia o quimioterapia y tislelizumab con la de quimioterapia con trastuzumab
- Evaluar la seguridad y la tolerabilidad de zanidatamab en combinación con quimioterapia o quimioterapia y tislelizumab.
- Evaluar el efecto de zanidatamab en combinación con quimioterapia o quimioterapia y tislelizumab en la calidad de vida relacionada con la salud (CVRS).
- Evaluar la farmacocinética (FC) de zanidatamab en combinación con quimioterapia o quimioterapia y tislelizumab.
- Evaluar la FC de tislelizumab en combinación con quimioterapia y zanidatamab.
- Evaluar la inmunogenicidad de zanidatamab en combinación con quimioterapia o quimioterapia y tislelizumab.
- Evaluar la inmunogenicidad de tislelizumab en combinación con quimioterapia y zanidatamab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Histologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISHpositivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment.
2.Assessable (measurable or non-measurable) disease as defined by RECIST 1.1.
3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization
4.Adequate organ function
5.Left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA)

1. Adenocarcinoma gastroesofágico positivo para HER2, localmente avanzado irresecable, recurrente o metastásico confirmado histológicamente (adenocarcinomas de estómago o esófago, incluida la unión gastroesofágica), definido como una expresión de 3+ de HER2 mediante IHQ o una expresión de 2+ de HER2 mediante IHQ con positividad de ISH según una evaluación centralizada. Los sujetos con adenocarcinoma esofágico no podrán optar a la quimiorradioterapia combinada en el momento de inclusión.
2. Enfermedad evaluable (medible o no medible) conforme a los criterios RECIST 1.1.
3. Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1, evaluado en los 3 días previos a la aleatorización.
4. Función hepática adecuada
5. Fracción de eyección del ventrículo izquierdo (FEVI) >= 50% determinada mediante ecocardiograma o ventriculografía isotópica en equilibrio (MUGA)

E.4

Principal exclusion criteria

1.Prior treatment with a HER2-targeted agent, with the exception of subjects who received HER2-targeted treatment for breast cancer > 5 years prior to initial diagnosis of GEA.
2.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
3.Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks prior to randomization. Stable, treated brain metastases are allowed (defined as subjects who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks prior to randomization).
4.Known history of or ongoing leptomeningeal disease (LMD).
5.Prior or concurrent invasive malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
6.Known active hepatitis
7.Any history of human immunodeficiency virus (HIV) infection
8.Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions’ requirements and screening guidance are eligible
9.Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF).
10.QTc Fridericia (QTcF) > 470 ms.
11.Ongoing Grade 2 or greater peripheral neuropathy

1. Tratamiento previo con un fármaco dirigido contra HER2, con la excepción de las pacientes que hayan recibido tratamiento dirigido contra HER2 para el cáncer de mama > 5 años antes del diagnóstico inicial de AGE.
2. Tratamiento previo con anticuerpos anti-PD-1, anti-PD-L1 y anti-PDL2 o cualquier otro anticuerpo o fármaco que actúe específicamente sobre la coestimulación de linfocitos T o vías de puntos de control inmunológico.
3. Metástasis en el sistema nervioso central (SNC) no tratadas, metástasis sintomáticas en el SNC o radioterapia para metástasis en el SNC en las 4 semanas anteriores a la aleatorización. Se permite la inclusión de pacientes con metástasis cerebrales tratadas y estables (esto es, pacientes que no reciben corticoesteroides ni anticonvulsivos, que son estables desde el punto de visto neurológico y que, antes de la aleatorización, llevan al menos 4 semanas sin signos de progresión radiológica).
4. Antecedentes conocidos o presencia de enfermedad leptomeníngea (ELM).
5. Neoplasia maligna invasiva previa o concomitante cuya evolución natural o tratamiento pueda interferir en la evaluación de la seguridad o la eficacia del régimen en investigación
6. Hepatitis activa conocida
7. Cualquier antecedente de infección por el virus de la inmunodeficiencia humana (VIH)
8. Infección conocida por el SARS-CoV-2; podrán participar sujetos con infección previa que se haya resuelto conforme a los requisitos de cada centro y las normas de selección.
9. Cardiopatía clínicamente significativa, como arritmia ventricular que requiera tratamiento, hipertensión no controlada o antecedentes de insuficiencia cardíaca congestiva (ICC) sintomática.
10. QTc según la fórmula de Fridericia (QTcF) > 470 ms.
11. Neuropatía periférica de grado 2 o superior en curso

E.5 End points

E.5.1

Primary end point(s)

●Progression-free survival (PFS) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by blinded independent central review (BICR)
●Overall survival (OS)

- Supervivencia sin progresión (SSP) conforme a los Criterios de evaluación de la respuesta en tumores sólidos, versión 1.1 (RECIST 1.1), evaluada mediante una revisión central independiente y enmascarada (RCIE).
- Supervivencia global (SG)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary PFS analysis and interim OS analysis are expected to occur approximately 1 month after the last subject is randomized. The primary analysis of OS is expected to be reached 14 months after the last subject is randomized.

El análisis principal de la SSP y el análisis intermedio de la SG se espera que ocurra aproximadamente un mes después de la aleatorización del último paciente. Se espera alcanzar el análisis principal de la SG 14 meses después de la aleatorización del último sujeto.

E.5.2

Secondary end point(s)

●Confirmed objective response rate (ORR) by RECIST 1.1, assessed by BICR
●Duration of response (DOR) by RECIST 1.1, assessed by BICR
●PFS by RECIST 1.1, per investigator assessment
●ORR by RECIST 1.1, per investigator assessment
●DOR by RECIST 1.1, per investigator assessment
●Frequency, type, severity, seriousness, and relatedness of adverse events (AEs)
●Frequency and severity of clinical laboratory abnormalities
●Change from baseline in health economics and outcomes research / patient-reported outcomes (HEOR/PRO) parameters
●PK parameters for zanidatamab
●PK parameters for tislelizumab
●Frequency, duration, and time of onset of anti zanidatamab antibodies and neutralizing antibodies, if applicable
●Frequency, duration, and time of onset of anti tislelizumab antibodies and neutralizing antibodies, if applicable

- Tasa de respuestas objetivas (TRO) confirmadas conforme a los criterios RECIST 1.1, según una RCIE.
- Duración de la respuesta (DR) evaluada mediante RCIE de acuerdo con los RECIST 1.1
- SSP conforme a los criterios RECIST 1.1, según la evaluación del investigador
- TRO conforme a los criterios RECIST 1.1, según la evaluación del investigador
- DR conforme a los criterios RECIST 1.1, según la evaluación del investigador
- Frecuencia, tipo, intensidad, gravedad y relación de los acontecimientos adversos (AA)
- Frecuencia e intensidad de las anomalías analíticas
- Variación con respecto al momento basal de los parámetros de economía sanitaria e investigación de resultados/resultados comunicados por los pacientes (ESIR/RCP).
- Parámetros FC de zanidatamab
- Parámetros FC de tislelizumab
- Frecuencia, duración y momento de aparición de los anticuerpos contra zanidatamab y de los anticuerpos neutralizantes, si procede.
- Frecuencia, duración y momento de aparición de los anticuerpos contra tislelizimab y de los anticuerpos neutralizantes, si procede.

E.5.2.1

Timepoint(s) of evaluation of this end point

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

Yes

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

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

Brazil

Canada

Chile

China

Korea, Democratic People's Republic of

Peru

Russian Federation

Serbia

Turkey

Ukraine

United States

Belgium

France

Germany

Italy

Netherlands

Poland

Portugal

Romania

Spain

United Kingdom

Argentina

Greece

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

Ultima visita del último sujeto

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

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:

321

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

828

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

338

F.4.2.2

In the whole clinical trial

1149

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

Ninguno

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

2021-08-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-08-25

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

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Orphan Designation Number:
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