Clinical Trials Register

Summary
EudraCT Number:	2017-002423-19
Sponsor's Protocol Code Number:	BGB-A317-301
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-12-18
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2017-002423-19

A.3

Full title of the trial

A Randomized, Open-label, Multicenter Phase 3 Study to Compare the Efficacy and Safety of BGB-A317 versus Sorafenib as First-Line Treatment in Patients with Unresectable Hepatocellular Carcinoma

A.3.1

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

Phase 3 Study of BGB-A317 Versus Sorafenib in Patients with Unresectable HCC

A.4.1

Sponsor's protocol code number

BGB-A317-301

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	BeiGene, Ltd. c/o BeiGene USA, 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	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, Inc.
B.5.2	Functional name of contact point	BeiGene Clinical Support
B.5.3	Address:
B.5.3.1	Street Address	USA
B.5.3.2	Town/ city	USA
B.5.3.4	Country	United States
B.5.6	E-mail	BeigeneClinicalSupportUS@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	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 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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	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	Nexavar 200 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Pharma AG
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	Nexavar
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	SORAFENIB TOSYLATE
D.3.9.1	CAS number	475207-59-1
D.3.9.4	EV Substance Code	SUB22347
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	200
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	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

Unresectable Hepatocellular Carcinoma

E.1.1.1

Medical condition in easily understood language

Unresectable Hepatocellular Carcinoma is a specific type of Liver cancer that is unable to be removed by surgery.

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	10019828
E.1.2	Term	Hepatocellular carcinoma non-resectable
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 compare overall survival (OS) between tislelizumab and sorafenib as first-line treatment in patients with unresectable hepatocellular carcinoma (HCC)

E.2.2

Secondary objectives of the trial

• To compare objective response rate (ORR) assessed by Blinded Independent Review Committee acc. to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 between tislelizumab and sorafenib
• To compare progression-free survival (PFS) assessed by BIRC according to RECIST v1.1 between tislelizumab and sorafenib
• To compare duration of response (DOR) assessed by BIRC according to RECIST v1.1 between tislelizumab and sorafenib
• To compare time to progression (TTP) between tislelizumab and sorafenib
• To compare health-related quality of life (HRQoL) between tislelizumab and sorafenib
• To compare tumor assessment outcomes (ie, ORR, PFS, DOR, TTP) assessed by the Investigator according to RECIST v1.1 between tislelizumab and sorafenib
• To compare disease control rate (DCR) and clinical benefit rate (CBR), assessed by BIRC and Investigator acc. to RECIST v1.1, between tislelizumab and sorafenib
• To compare safety and tolerability of tislelizumab versus sorafenib

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Title: SAFETY RUN-IN SUBSTUDY INVESTIGATING SAFETY, TOLERABILITY, PHARMACOKINETICS AND PRELIMINARY ANTITUMOR ACTIVITY OF ANTI-PD-1 MONOCLONAL ANTIBODY BGB-A317 IN JAPANESE PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA
Protocol Identifier: BGB-A317-301 Substudy
Primary Study Objectives:
• To assess the safety and tolerability of BGB-A317 in Japanese patients with hepatocellular carcinoma (HCC)
• To confirm the pivotal Phase 3 dose of BGB-A317 in Japanese patients
• To characterize the pharmacokinetics of BGB-A317 in Japanese patients
Secondary Study Objectives:
• To assess the preliminary antitumor activity of BGB-A317
• To assess host immunogenicity to BGB-A317

E.3

Principal inclusion criteria

1. Histologically confirmed diagnosis of HCC
2. Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach
3. No prior systemic therapy for HCC (with the exception of HCC patients enrolled in the safety run-in substudy [Japan only])
4. Measurable disease
5. Child-Pugh score A
6. Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
7. Adequate organ function

E.4

Principal exclusion criteria

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
2. Tumor thrombus involving main trunk of portal vein or inferior vena cava
3. Loco-regional therapy to the liver within 28 days before randomization
4. Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
5. Bleeding or thrombotic disorder or any prescribed anticoagulant requiring therapeutic international normalized ratio monitoring (eg, warfarin or similar agents) at Screening, or within 6 months before randomization/enrollment
6. Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse
7. Patient with any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before randomization
8. History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy
9. QT interval corrected for heart rate (QTc) (corrected by Fridericia’s method) > 450 msec at Screening

E.5 End points

E.5.1

Primary end point(s)

• Overall Survival (OS) – defined as the time from the date of randomization to the date of death due to any cause

E.5.1.1

Timepoint(s) of evaluation of this end point

OS assessed by Blinded Independent Review Committee (BIRC)

E.5.2

Secondary end point(s)

• Overall Response Rate (ORR) as assessed by BIRC – defined as the proportion of patients with a documented CR or PR per RECIST v1.1
• Progression-free survival (PFS)– defined as the time from the date of randomization to the date of the first objectively documented tumor progression, assessed by BIRC per RECIST v1.1, or death, whichever occurs first
• Duration of response (DOR) – defined as the time from the first determination of an objective response, assessed by BIRC per RECIST v1.1, until the first documentation of progression or death, whichever occurs first
• Time to progression (TTP) – defined as the time from the date of randomization to the date of the first objectively documented tumor progression, assessed by BIRC per RECIST v1.1
• Health-related quality of life (HRQoL)
• Tumor assessment (ie, ORR, PFS, DOR and TTP), assessed by Investigator per RECIST v1.1
• Disease control rate (DCR) – defined as the proportion of patients whose best overall response (BOR) is CR, PR, or SD, assessed by BIRC and Investigator per RECIST v1.1
• Clinical benefit rate (CBR) – defined as the proportion of patients who have CR, PR, or SD of ≥ 24 weeks in duration, assessed by BIRC and Investigator per RECIST v1.1
• Safety assessment

E.5.2.1

Timepoint(s) of evaluation of this end point

• ORR by BIRC
• PFS by BIRC
• DOR by BIRC
• TTP by BIRC
• HRQoL
• Tumor assessments (ORR, PFS, DOR, and TTP) assessed by Investigator per RECIST v1.1
• DCR by BIRC and Investigator
• CBR by BIRC and Investigator
• Safety assessment (eg, new adverse events [AEs], AEs present at baseline that worsen in severity during the study, and clinical laboratory abnormalities)

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

European Union

Taiwan

China

Japan

United States

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:

402

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

268

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

175

F.4.2.2

In the whole clinical trial

670

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, will be offered the opinion to continue on treatment in a BeiGene clinical trial until it is commercially available in the country.

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

2018-12-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-12-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-12-15

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