Clinical Trials Register

Summary
EudraCT Number:	2018-000587-28
Sponsor's Protocol Code Number:	BGB-A317-306
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:	2021-01-22
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

2018-000587-28

A.3

Full title of the trial

A Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Efficacy and Safety of Tislelizumab (BGB-A317) in Combination with Chemotherapy as First-Line Treatment in Patients with Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Studio randomizzato, controllato con placebo, in doppio cieco, di Fase 3 per valutare l’efficacia e la sicurezza di tislelizumab (BGB-A317) in combinazione con chemioterapia come trattamento di prima linea in pazienti con carcinoma esofageo a cellule squamose ricorrente o metastatico, non resecabile, localmente avanzato

A.3.1

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

Study compares the effects and safety of Tislelizumab (BGB-A317) plus chemotherapy with placebo (an inactive substance) plus chemotherapy for locally advanced recurrent or metastatic esophageal squamous cell carcinoma.

Studio che confronta gli effetti e la sicurezza di tislelizumab (BGB-A317) più chemioterapia con placebo (una sostanza inattiva) più chemioterapia per carcinoma esofageo a cellule squamose ricorrente o metastatico localmente avanzato

A.3.2

Name or abbreviated title of the trial where available

NAP

A.4.1

Sponsor's protocol code number

BGB-A317-306

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	BeiGene Ltd.
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	BeiGene, Ltd.
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	BeiGene, Ltd.
B.5.2	Functional name of contact point	Clinical Trial Information Email
B.5.3	Address:
B.5.3.1	Street Address	2955 Campus Drive, Suite 200
B.5.3.2	Town/ city	San Mateo
B.5.3.3	Post code	CA 94403
B.5.3.4	Country	United States
B.5.4	Telephone number	000000
B.5.5	Fax number	000000
B.5.6	E-mail	clinicaltrials@beigene.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	Tislelizumab
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.3.9.4	EV Substance Code	SUB189550
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	100
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	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	Xeloda
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
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	Xeloda
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.3.9.2	Current sponsor code	NA
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	Yes
D.3.11.13.1	Other medicinal product type	chemioterapico
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	Cisplatinum Accord
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare Limited
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	Cisplatin
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	CISPLATINUM
D.3.9.2	Current sponsor code	NA
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	1
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	Yes
D.3.11.13.1	Other medicinal product type	chemioterapico
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.2.1.1.1	Trade name	Fluorouracil-GRY
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA 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	Fluorouracil
D.3.2	Product code	[NA]
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	FLUOROURACILE
D.3.9.2	Current sponsor code	NA
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	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	Yes
D.3.11.13.1	Other medicinal product type	chemioterapico
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.2.1.1.1	Trade name	Paclitaxel AqVida
D.2.1.1.2	Name of the Marketing Authorisation holder	AqVida 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	Paclitaxel AqVida
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	PACLITAXEL
D.3.9.2	Current sponsor code	NA
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	6
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	Yes
D.3.11.13.1	Other medicinal product type	chemioterapico
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	Yes
D.2.1.1.1	Trade name	Oxaliplatin AqVida
D.2.1.1.2	Name of the Marketing Authorisation holder	AqVida 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	Oxaliplatin AqVida
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.3.9.2	Current sponsor code	NA
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	Yes
D.3.11.13.1	Other medicinal product type	chemioterapico
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	Yes
D.2.1.1.1	Trade name	Fluorouracile AHCL
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare S.L.U.
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	Fluorouracile
D.3.2	Product code	[NA]
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	FLUOROURACILE
D.3.9.2	Current sponsor code	NA
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	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	Yes
D.3.11.13.1	Other medicinal product type	chemioterapico
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	Yes
D.2.1.1.1	Trade name	Fluorouracil Accord
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Lithuania
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	Fluorouracile
D.3.2	Product code	[NA]
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	FLUOROURACILE
D.3.9.2	Current sponsor code	NA
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	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	Yes
D.3.11.13.1	Other medicinal product type	chemioterapico

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma (ESCC)

Carcinoma esofageo a cellule squamose (ESCC) ricorrente o metastatico, non resecabile, localmente avanzato

E.1.1.1

Medical condition in easily understood language

Unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma (ESCC)

Carcinoma esofageo a cellule squamose (ESCC) ricorrente o metastatico, non resecabile, localmente 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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10055476
E.1.2	Term	Esophageal squamous cell carcinoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To evaluate and compare the PFS assessed per RECIST version (v) 1.1 following treatment with tislelizumab in combination with chemotherapy compared to placebo in combination with chemotherapy when given as first-line treatment in patients with unresectable, locally advanced recurrent or metastatic ESCC

- To evaluate and compare the overall survival (OS) following treatment with tislelizumab in combination with chemotherapy compared to placebo in combination with chemotherapy when given as first-line treatment in patients with unresectable, locally advanced recurrent or metastatic ESCC

- Valutare e confrontare la sopravvivenza libera da progressione (PFS) valutata in base ai Criteri di valutazione della risposta nei tumori solidi (RECIST) versione (v) 1.1 dopo il trattamento con tislelizumab in combinazione con chemioterapia rispetto a placebo in combinazione con chemioterapia quando somministrato come trattamento di prima linea in pazienti con carcinoma esofageo a cellule squamose (ESCC) ricorrente o metastatico, non resecabile, localmente avanzato

- Valutare e confrontare la sopravvivenza globale (OS) dopo il trattamento con tislelizumab in combinazione con chemioterapia rispetto a placebo in combinazione con chemioterapia quando somministrato come trattamento di prima linea in pazienti con ESCC ricorrente o metastatico, non resecabile, localmente avanzato

E.2.2

Secondary objectives of the trial

- To evaluate and compare the efficacy of tislelizumab in combination with chemotherapy compared to placebo in combination with chemotherapy as a first-line treatment in unresectable, locally advanced recurrent or metastatic ESCC as measured by ORR and DOR assessed per RECIST v1.1

- To evaluate and compare Patient Reported Outcomes (PROs) of healthrelated quality of life (HRQoL) between tislelizumab in combination with chemotherapy compared to placebo in combination with chemotherapy

- To compare the safety between tislelizumab in combination with chemotherapy and placebo in combination with chemotherapy

- Valutare e confrontare l’efficacia di tislelizumab in combinazione con chemioterapia rispetto a placebo in combinazione con chemioterapia come trattamento di prima linea nell’ESCC ricorrente o metastatico, non resecabile, localmente avanzato, misurata mediante il tasso di risposta obiettiva (ORR) e la durata della risposta (DOR) valutati come dal RECIST v1.1

- Valutare e confrontare gli esiti riferiti dal paziente (PRO) della qualità della vita correlata alla salute (HRQoL) tra tislelizumab in combinazione con chemioterapia rispetto a placebo in combinazione con chemioterapia

- Confrontare la sicurezza tra tislelizumab in combinazione con chemioterapia e placebo in combinazione con chemioterapia

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Pathologically (histologically) confirmed diagnosis of ESCC
Note: Patients with adenocarcinoma differentiation < 5% of the viable tumor sample are eligible
- Stage IV unresectable ESCC at first diagnosis OR unresectable, locally advanced recurrent or metastatic disease (per AJCC 7th Edition), if there is prior neoadjuvant/adjuvant therapy with platinum-based chemotherapy, a treatment-free interval of at least 6 months is required

- Diagnosi di ESCC confermata a livello patologico (istologico)
Nota: pazienti con una differenziazione dell'adenocarcinoma < 5% del campione tumorale sono elegibili
- ESCC non resecabile allo Stadio IV, alla prima diagnosi O malattia ricorrente o metastatica, non resecabile, localmente avanzata (secondo l’AJCC 7a Edizione), se è stata effettuata una precedente terapia neoadiuvante/adiuvante con chemioterapia a base di platino, è richiesto un intervallo senza trattamento di almeno 6 mesi.

E.4

Principal exclusion criteria

- Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation
- Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC
Note: Patients with prior systemic concurrent chemotherapy in concurrent chemoradiotherapy are eligible
- Received prior therapies targeting PD-1, PD-L1 or PD-L2
- Patients with evidence of fistula (either esophageal/bronchial or esophageal/aorta)
- Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention)
- Evidence of complete esophageal obstruction not amenable to treatment
- Unintentional weight loss = 5% within one month prior to randomization or Nutritional Risk Index (NRI) < 83.5 per investigator's choice
- Patients receiving chemotherapy doublet C (platinum and and paclitaxel) must not have peripheral neuropathy = Grade 2 at baseline

- Trattamento di radioterapia palliativa per ESCC entro 4 settimane dall’inizio del trattamento dello studio
- Terapia sistemica pregressa per ESCC ricorrente o metastatico, non resecabile, localmente avanzato
Nota: pazienti con precedente chemioterapia concomitante sistemica con concomitante radiochemioterapia sono elegibili
- Precedenti terapie mirate alla proteina di morte cellulare programmata (PD-1) o al ligando 1 della proteina di morte programmata (PD-L1) o al ligando 2 della proteina di morte programmata (PD-L2)
- Pazienti con evidenza di fistola (esofagea / bronchiale o esofagea / aorta)
- Versamento pleurico incontrollabile, versamento pericardico o ascite che richiedono drenaggio frequente o intervento medico (recidiva clinicamente significativa che richiede un ulteriore intervento entro 2 settimane dall’intervento)
- Evidenza di ostruzione esofagea completa non suscettibile di trattamento
- Perdita di peso non intenzionale del > = 5% entro 1 mese prima della randomizzazione o Indice di rischio nutritivo (NRI) < 83.5 per scelta dello sperimentatore.
- Pazienti che ricevono la doppietta di chemioterapia C (platino e paclitaxel) non devono avere neuropatia periferica = Grado 2 a livello basale

E.5 End points

E.5.1

Primary end point(s)

- PFS - defined as the time from the date of randomization to the date of first documentation of disease progression assessed per RECIST v1.1 or death, whichever occurs first
- OS - defined as the time from the date of randomization until the date of death due to any cause

- PFS: è definita come intervallo di tempo trascorso dalla data della randomizzazione alla data della prima documentazione di progressione della malattia, valutato secondo i criteri RECIST v1.1, o al decesso, a seconda di quale evento si verifichi per primo
- OS: è definita come l’intervallo di tempo trascorso dalla data della randomizzazione alla data del decesso per qualsiasi causa

E.5.1.1

Timepoint(s) of evaluation of this end point

PFS and OS – analysis will be carried out at approximately 31 months

PFS and OS – l'analisi sarà effettuata a circa 31 mesi

E.5.2

Secondary end point(s)

- ORR - defined as the proportion of patients whose best overall response (BOR) is complete response (CR) or partial response (PR)
- DOR - defined as the time from the first determination of an objective response until the first documentation of progression
- HRQoL assessment of the patient's overall health status
- PFS, ORR, and DOR
- The incidence and severity of adverse events

- ORR - definito come la proporzione di pazienti la cui migliore risposta globale (BOR) è la risposta completa (CR) o la risposta parziale (PR)
- DOR - definito come il tempo dalla prima determinazione di una risposta obiettiva fino alla prima documentazione di progressione
- Valutazione HRQoL dello stato di salute generale del paziente
- PFS, ORR e DOR
- L'incidenza e la gravità degli eventi avversi

E.5.2.1

Timepoint(s) of evaluation of this end point

- ORR - As assessed per RECIST v1.1
- DOR - As assessed per RECIST v1.1 or death, whichever comes first
- HRQoL - European EORTC QLQ-C30 index, the European esophageal cancer specific module EORTC QLQ-OES18, and the generic health state instrument EuroQol 5D (EQ-5D-5L)
- PFS, ORR, and DOR- As assessed by the investigator per RECIST v1.1
- The incidence and severity of adverse events according to NCI-CTCAE v4.03

- ORR - Come valutato in base al RECIST v1.1
- DOR - Valutato in base a RECIST v1.1 o morte, a seconda dell'evento che si verifica per primo
- HRQoL - Indice europeo EORTC QLQ-C30, modulo europeo specifico per il cancro esofageo EORTC QLQ-OES18 e lo strumento generico sullo stato di salute EuroQol 5D (EQ-5D-5L)
- PFS, ORR e DOR- Come valutato dallo sperimentatore in base a RECIST v1.1
- L'incidenza e la gravità degli eventi avversi secondo NCI-CTCAE v4.03

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

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity, Tolerability

Immonogenicità, Tollerabilità

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

Australia

China

Japan

Korea, Republic of

Russian Federation

Taiwan

United States

Belgium

Czechia

France

Germany

Italy

Poland

Romania

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

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:

312

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

168

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

137

F.4.2.2

In the whole clinical trial

480

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)

Patients assigned to tislelizumab, who in the opinion of the Investigator, continue to benefit from tislelizumab at study termination, may be offered the option to continue on treatment in a BeiGene clinical trial until it is commercially available in the country.

Ai pazienti assegnati a tislelizumab, che secondo il parere dello sperimentatore, continuano a beneficiare di tislelizumab al temine dello studio, può essere offerta la possibilità di continuare il trattamento in un studio clinico del promotore BeiGene fino a quando non sarà commercialmente disponibile nel paese.

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-05-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-02-20

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

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