Clinical Trials Register

Summary
EudraCT Number:	2019-002105-22
Sponsor's Protocol Code Number:	BGB-A317-210/TIRHOL
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-04-07
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

France - ANSM

A.2

EudraCT number

2019-002105-22

A.3

Full title of the trial

A Phase 2, Multicenter, Open-Label Study of Tislelizumab (BGB-A317) in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma

A.3.1

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

Study of Tislelizumab in Patients with Relapsed or Refractory Hodgkin Lymphoma

A.4.1

Sponsor's protocol code number

BGB-A317-210/TIRHOL

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	LYSARC
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-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	China
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	LYSARC
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	CHU Lyon Sud - bâtiment 2D
B.5.3.2	Town/ city	Pierre Bénite cedex
B.5.3.3	Post code	69495
B.5.3.4	Country	France
B.5.4	Telephone number	33472669333
B.5.5	Fax number	33426074055
B.5.6	E-mail	tirhol@lysarc.org

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	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.3.9.2	Current sponsor code	BGB-A317
D.3.9.4	EV Substance Code	SUB193656
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)	Yes
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

Refractory/relapse Hodgkin Lymphoma

E.1.1.1

Medical condition in easily understood language

Refractory/relapse Hodgkin Lymphoma

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10020328
E.1.2	Term	Hodgkin's lymphoma
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 the efficacy of tislelizumab in patients with relapsed/refractory classical Hodgkin lymphoma, as measured by the overall response rate per the Lugano Classification (Cheson et al 2014) and determined by the investigator.

E.2.2

Secondary objectives of the trial

Efficacy endpoints assessed by the investigator using the Lugano Classification:
 Complete response rate, defined as the proportion of patients who achieve a best
response of complete response
 Duration of response, defined as the time from the date that response criteria are
first met to the date that disease progression is objectively documented or death,
whichever occurs first
 Time to response, defined as the time from the date of the first dose of
tislelizumab to the time the response criteria are first met
 Safety and tolerability of tislelizumab, as defined by:
 The incidence and severity of adverse events according to National Cancer
Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
 Changes in vital signs, physical findings, and clinical laboratory results

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female ≥ 18 years
2. Histologically confirmed diagnosis of relapsed or refractory cHL
3. Relapsed cHL (disease progression after PR or CR to the most recent therapy) or refractory cHL (failure to achieve PR or CR to most recent therapy).
Patients will be allocated to one of two cohorts based on the following criteria:
- Cohort 1: Relapsed or refractory to prior autologous hematopoietic stem cell transplant (HSCT) and brentuximab vedotin
--Has failed to achieve a response or progressed after autologous HSCT and failed to achieve a response or progressed after brentuximab vedotin
-- Not a candidate for additional autologous or allogeneic HSCT
- Cohort 2: Relapsed or refractory to salvage chemotherapy, including brentuximab vedotin, and as not received prior autologous or allogeneic HSCT
--is not a candidate for autologous or allogeneic HSCT due to disease refractory to
salvage chemotherapy (did not achieve a PR or CR)
-- has received at least 2 prior systemic chemotherapy regimens for cHL and failed to achieve a response or progressed after brentuximab vedotin
4. Measurable disease defined as ≥ 1 FDG-avid nodal lesion that is > 1.5 cm in the longest diameter, or ≥ 1 FDG-avid extra-nodal lesion (eg, hepatic nodules) that is > 1 cm in the longest diameter
5. Able to provide fresh or archival tumor tissues (formalin-fixed paraffin-embedded [FFPE] blocks or approximately 15 freshly cut, unstained FFPE slides) from an evaluable core or excisional biopsy with an associated pathological report
6. ECOG performance status of 0 or 1
7. Life expectancy ≥ 12 weeks
8. Adequate organ function, as indicated by the following laboratory values:
a. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L, independent of growth factor support
within 7 days of first dose
b. Platelet ≥ 75 x 109/L, independent of growth factor support within 7 days of first dose
c. Hemoglobin (Hgb) ≥ 8 g/dL or ≥ 5 mmol/L
d. Creatinine clearance > 30 mL/min
e. AST (SGOT) and ALT (SGPT) ≤ 2.5 x the ULN or ≤ 5 x ULN if liver lymphoma involvement is present
f. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin level < 4 x ULN for patients with
Gilbert syndrome)
9. No evidence of dyspnea at rest and a pulse oximetry of > 92% while breathing room air
of dyspnea at rest and a pulse oximetry of > 92% while breathing room air
10. DLCO (adjusted for alveolar volume) > 60% of predicted value; FEV1 and FVC,
FEV1/ FVC all > 50% predicted value
11. Female patients of childbearing potential must be willing to use a highly effective method
of contraception for the duration of the study and for ≥ 120 days after the last dose of
tislelizumab, and have a negative urine or serum pregnancy test within 7 days before the
first dose of study drug.
12. Males are eligible to enter and participate in the study if they have been vasectomized or
if they agree to use barrier contraception with other highly effective methods during the study treatment period and for ≥ 120 days after the last dose of
tislelizumab
13. Ability to provide written informed consent and can understand and comply with the
requirements of the study

E.4

Principal exclusion criteria

1. Nodular lymphocyte-predominant Hodgkin lymphoma or gray zone lymphoma
2. Prior allogeneic hematopoietic stem cell transplantation
3. History of severe hypersensitivity reaction to monoclonal antibodies
4. New York Heart Association (NYHA) class III or IV heart failure, unstable angina,
severe uncontrolled ventricular arrhythmia, electrocardiographic evidence of acute
ischemia, or myocardial infarction within 6 months of first day of screening
5. Prior malignancy within the past 3 years except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or other site for which in situ carcinoma has metastatic potential
6. Prior therapy targeting PD-1 or PD-L1, anti-PD-L2, or anti CTLA-4 agent
7. Has received:
- Systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to Cycle 1 Day 1
- Recent treatment with another monoclonal antibody within 4 weeks prior to Cycle 1 Day 1
- Investigational treatment or device within 4 weeks (or 5 half-lives, whichever is shorter) prior to Cycle 1 Day 1 and may qualify for the study if all other criteria are met)
8. Active autoimmune disease or history of autoimmune disease that may relapse
- Patients with the following are not excluded and may proceed to further screening:
Vitiligo, eczema, type I diabetes mellitus, and endocrine deficiencies including thyroiditis managed with replacement hormone and/or physiologic corticosteroids
- Patients with the following should be evaluated for the presence of target organ involvement and the potential need for systemic treatment, but should otherwise be eligible: Rheumatoid arthritis and/or other arthropathies, Sjögren’s syndrome, or
psoriasis controlled with topical medication, and patients with positive serology such
as positive antinuclear antibody or anti-thyroid antibody
9. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of the first dose of tislelizumab
 Adrenal replacement doses of ≤ 10 mg daily prednisone equivalent in the absence of
active autoimmune disease
 Topical, ocular, intra-articular, intranasal, and inhalational corticosteroid (with
minimal systemic absorption)
 A brief course of corticosteroid for prophylaxis (eg, contrast dye allergy) or for
treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction
caused by contact allergen)
10. History of interstitial lung disease or noninfectious pneumonitis or has evidence of
interstitial lung disease or noninfectious pneumonitis
11. Serious acute or chronic infection requiring systemic therapy
12. Known central nervous system (CNS) lymphoma
13. Underlying medical conditions that, in the investigator’s opinion, will render the
administration of study drug hazardous or obscure the interpretation of toxicity or AEs
14. Known history of infection with HIV, human T-cell lymphotropic virus-1, or human
T-cell lymphotropic virus-2
15. Serologic status reflecting active hepatitis B or C infection as follows:
 Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible only if hepatitis B virus (HBV) DNA is undetectable by an assay with sensitivity ≤ 20 IU/mL. If so, patients may either undergo regularly scheduled monitoring of
HBV DNA or less frequent monitoring of HBV DNA while on prophylactic antiviral medication as defined by regional standard of care.
hematopoietic stem cell transplantation within 100 days of first dose of
tislelizumab
17. CAR-T therapy within 12 months prior to the first dose of study drug
18. Use of any live vaccine against infectious diseases (eg, influenza, varicella, etc) within 4 weeks (28 days) of the first dose of tislelizumab, and any intended use within 60 days after the last dose of tislelizumab
19. Major surgery within 4 weeks of the first dose of tislelizumab
20. Pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
21. Has hypersensitivity to tislelizumab or any of its excipients
22. Concurrent participation in another therapeutic clinical trial

E.5 End points

E.5.1

Primary end point(s)

The overall response rate, defined as the proportion of patients who achieve a best response of complete response or partial response by PET-CT per the Lugano Classification (Cheson et al 2014) and determined by the investigator.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year

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

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)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

E.8.2.3

Other

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

Australia

United States

E.8.7

Trial has a data monitoring committee

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

1 year after the last patient is enrolled

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.4.2.2

In the whole clinical trial

100

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 who remain on study treatment at the end of the study may have an opportunity to receive tislelizumab in a separate rollover or extension protocol.

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

2020-05-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-07

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

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