Clinical Trials Register

Summary
EudraCT Number:	2016-005115-41
Sponsor's Protocol Code Number:	TG4010.24
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-06-20
Trial results	View 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

Belgium - FPS Health-DGM

A.2

EudraCT number

2016-005115-41

A.3

Full title of the trial

A phase II study evaluating the efficacy and the safety of first-line chemotherapy combined with TG4010 and nivolumab in patients with advanced non-squamous Non-Small-Cell Lung Cancer (NSCLC)

A.3.1

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

A study assessing the combination of TG4010 and nivolumab with standard treatment in patients with advanced non small cell lung cancer.

A.4.1

Sponsor's protocol code number

TG4010.24

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	Transgene S.A.
B.1.3.4	Country	France
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	Transgene S.A
B.4.2	Country	France
B.4.1	Name of organisation providing support	Bristol Myers Squibb
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	Transgene S.A.
B.5.2	Functional name of contact point	Medical Affairs Secretariat
B.5.3	Address:
B.5.3.1	Street Address	400 Boulevard Gonthier d’Andernach - Parc d’Innovation - CS80166
B.5.3.2	Town/ city	Illkirch Graffenstaden Cedex
B.5.3.3	Post code	67405
B.5.3.4	Country	France
B.5.4	Telephone number	+33388 27 91 55
B.5.5	Fax number	+33388 27 91 41
B.5.6	E-mail	clinical.trials@transgene.fr

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	Mesmulogene ancovacivec
D.3.2	Product code	TG4010
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Mesmulogene ancovacivec
D.3.9.3	Other descriptive name	MVATG9931
D.3.10	Strength
D.3.10.1	Concentration unit	PFU plaque forming unit
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1E+08 to 5E+08
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
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	Opdivo (nivolumab)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma
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.3.4	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	Nivolumab
D.3.9.3	Other descriptive name	NIVOLUMAB
D.3.9.4	EV Substance Code	SUB122750
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.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

Stage IIIB-IV non small cell lung cancer (NSCLC)

E.1.1.1

Medical condition in easily understood language

Advanced non small cell lung cancer

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	10025055
E.1.2	Term	Lung cancer non-small cell stage IV
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 anti-tumor activity in terms of objective response rate (ORR) by using RECIST 1.1 in chemotherapy-naïve and immunotherapy-naïve advanced, non-squamous NSCLC patients with PD-L1 membrane staining on <50% of tumor cells receiving first-line chemotherapy (pemetrexed + carboplatin or cisplatin followed by pemetrexed maintenance therapy) plus TG4010 and nivolumab.

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy with respect to:
a) Progression Free Survival (PFS)
b) Disease Control Rate (DCR)
c) Overall Survival (OS)
• To describe duration of response (DoR)
• To evaluate the safety profile

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Female or male patients age > 18 years-old
• ECOG performance Status 0 or 1 at study entry
• Life expectancy of at least 3 months
• Histologically confirmed non-squamous NSCLC (adenocarcinoma, large cell carcinoma, undifferentiated carcinoma or other)
• Stage IIIB-IV cancer or delayed relapse of any stage not amenable to surgery or radiotherapy with curative intent.
• PD-L1 expression by immunohistochemistry in < 50% of tumor cells
• Patients must be chemotherapy-naïve for the advanced stage of the disease. Previous neoadjuvant and/or adjuvant chemotherapy is allowed for patients who successfully underwent complete radical surgery and if last treatment was administered more than 12 months prior to the start of the study treatment.
• At least one measurable lesion by CT scan based on RECIST 1.1 performed within 28 days prior to start of study treatment
• Adequate hematological, hepatic, and renal functions
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug plus 30 days for a total of 5 months post-treatment completion. Highly effective contraception are defined in the protocol.
• Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 90 days for a total of 7 months post-treatment completion

E.4

Principal exclusion criteria

• Patients having CNS metastases
• Patients with pericardial effusion
• Prior exposure to cancer immunotherapy including cancer vaccines, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-Lymphocyte antigen-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Patients with EGFR activating mutations or ALK- rearrangements leading to eligibility for TKI treatment (tests mandatory)
• Prior history of other malignancy except basal cell carcinoma of the skin, cervical intra epithelial neoplasia, and other cancer curatively treated with no evidence of disease for at least 3 years
• Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
• Patients with an active, known or suspected autoimmune disease
• Patient with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Patients with grade ≥ 2 neuropathy
• Signs or symptoms of infection within 14 days prior to start of study treatment or active infection requiring systemic therapy
• Positive serology for HIV or HCV; presence in the serum of the antigens HBs at baseline
• Patient with any underlying medical condition that the treating physician considers might be aggravated by treatment or which is not controlled (e.g., elevated troponin or creatinine, uncontrolled diabetes)
• History of any of the following cardiovascular conditions within 12 months of enrollment
• Left ventricular ejection fraction less than the Lower Limit of Normal as assessed by echocardiography (or MUGA scan)
• Patient with major surgery or radiotherapy within 3 weeks prior to the start of the study treatment. However, prior surgery or radiation therapy aimed at local palliation or attempted local disease control (except in case of thoracic radiotherapy) is permitted but has to be completed 2 weeks before treatment start
• Pregnant or nursing (lactating) women
• Patients with an organ allograft
• Any known allergy to eggs, gentamicin or history of allergy or hypersensitivity to study drug components
• Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatments

E.5 End points

E.5.1

Primary end point(s)

• Objective Response Rate (ORR)

E.5.1.1

Timepoint(s) of evaluation of this end point

ORR: tumor assessment evaluated by RECIST 1.1 every 6 weeks from start of treatment until documented progression or for a period of 9 months after start of study treatment, whichever occurs first. Beyond 9 months of treatment, the evaluations will be performed every 12 weeks until documented progression

E.5.2

Secondary end point(s)

• Progression Free Survival (PFS)
• Disease Control Rate (DCR)
• Overall Survival (OS)
• Duration of response (DoR)
• Safety profile

E.5.2.1

Timepoint(s) of evaluation of this end point

PFS, DCR, DoR: tumor assessment evaluated by RECIST 1.1 every 6 weeks from start of treatment until documented progression or for a period of 9 months after start of study treatment, whichever occurs first. Beyond 9 months of treatment, the evaluations will be performed every 12 weeks until documented progression

OS: after termination of study treatment, patients will be followed for survival on a 3-monthly basis

Safety: evaluated throughout the study

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

Belgium

Denmark

France

Hungary

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

Date of last patient inclusion + 18 months

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:

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

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)

As per normal standard of care for this condition

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

2017-11-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-11-02

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