Clinical Trials Register

Summary
EudraCT Number:	2018-001517-32
Sponsor's Protocol Code Number:	MS200647-0037
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:	2018-09-18
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

2018-001517-32

A.3

Full title of the trial

An Adaptive Phase III Multicenter, Randomized, Open-
Label, Controlled Study of M7824 (bitrafusp alfa) versus
Pembrolizumab as a First-line Treatment in Patients with PD-L1 Expressing
Advanced Non-small Cell Lung Cancer

A.3.1

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

Clinical study phase III, first line treatment of patients with lung cancer
comparing investigational drug M7824 vs Pembrolizumab.

A.4.1

Sponsor's protocol code number

MS200647-0037

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	Merck Healthcare KGaA
B.1.3.4	Country	Germany
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	Merck KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck KGaA
B.5.2	Functional name of contact point	Communication Center Merck KGaA
B.5.3	Address:
B.5.3.1	Street Address	Frankfurter Strasse 250
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 6151 72 5200
B.5.5	Fax number	+49 6151 72 2000
B.5.6	E-mail	service@merckgroup.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.3.2	Product code	M7824
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.3.9.2	Current sponsor code	MSB0011359C
D.3.9.3	Other descriptive name	M7824
D.3.9.4	EV Substance Code	SUB179957
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	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	KEYTRUDA 25 mg/ml concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp &Dohme Limited
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	PEMBROLIZUMAB
D.3.9.4	EV Substance Code	SUB167136
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	25
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: 3
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	KEYTRUDA 50 mg Powder for concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp &Dohme Limited
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	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	PEMBROLIZUMAB
D.3.9.4	EV Substance Code	SUB167136
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	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	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

Non-small Cell Lung Cancer

E.1.1.1

Medical condition in easily understood language

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10029522
E.1.2	Term	Non-small cell lung cancer stage IV
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 demonstrate improvement in PFS with M7824 compared with
pembrolizumab
To demonstrate improvement in OS with M7824 compared with
pembrolizumab

E.2.2

Secondary objectives of the trial

Safety
-To evaluate the safety and tolerability
of M7824 compared with pembrolizumab

Efficacy
-To evaluate the objective response of M7824 compared with
pembrolizumab
- To evaluate the DOR of M7824 compared with pembrolizumab

PK
-To characterize pharmacokinetic (PK) profile of M7824

Immunogenicity
-To characterize the immunogenicity
of M7824

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. ≥ 18 years of age inclusive, at the time of signing the informed consent

2. histologically confirmed diagnosis of advanced NSCLC and:
a. Have not received prior systemic therapy treatment for their advanced/Stage IV
NSCLC. Completion of treatment with cytotoxic chemotherapy, biological therapy,
and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy
was completed at least 6 months prior to the diagnosis of metastatic disease.
Confirmation of resolution of toxic effects of previous neoadjuvant/adjuvant
chemotherapy therapy to Grade ≤ 1. For radiation toxicity or prior major surgeries,
participants should have recovered from side effects and/or complications.
b. Have measurable disease based on RECIST 1.1
c. Have a life expectancy of at least 3 months
d. Availability of tumor tissue (< 6 months old, excluding bone biopsies)
before the first dose is mandatory to determine PD-L1 expression level prior to enrollment
e. PD-L1 high status by central testing is required

(other protocol defined criteria could apply)

E.4

Principal exclusion criteria

1. Participants with nonsquamous NSCLC histologies whose tumor
harbors any of the following molecular alterations and targeted therapy
is locally approved:
a. EGFR sensitizing (activating) mutation
b. ALK translocation(s) associated with responsiveness to ALK tyrosine
kinase inhibitors
c. ROS1 rearrangement(s) associated with responsiveness to ROS1
tyrosine kinase inhibitors
d. BRAF V600E mutation
2. Has received major surgery within 4 weeks prior to the first dose of study intervention;
received thoracic RT of > 30 Gy within 6 months prior to the first dose of study
7. Known severe hypersensitivity reactions (Grade = 3 National Cancer
Institute
[NCI] Common Terminology Criteria for Adverse Events [CTCAE] v5.0) to
investigational product (M7824 or pembrolizumab) or any components in
their formulations, or uncontrolled asthma (ie, 3 or more features of partially
controlled asthma)
8. Receipt of any organ transplantation
9. Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required
oral or IV steroids
10. Significant acute or chronic infections
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with participation for the full
duration of the study, or is not in the best interest of the participant, in the opinion of the
treating Investigator. Participants with history of bleeding diathesis or recent
major bleeding events considered by the Investigator as high risk for
investigational drug treatment, such as patients with clinically relevant
bleeding events of hemoptysis Grade = 2 within the last month, are also excluded.
12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways)
intervention.
13. Previous malignant disease
14. Has active CNS metastases causing clinical symptoms or metastases that require
therapeutic intervention and/or carcinomatosis meningitis
15. Active autoimmune disease that has required systemic treatment in past 1 year OR is
receiving systemic steroid therapy < 3 days prior to the first dose of study intervention or
receiving any other form of immunosuppressive medication.
16. Is expected to require any other form of systemic or localized antineoplastic therapy
while on study (including maintenance therapy with another agent for NSCLC, RT,
and/or surgical resection)

(other protocol defined criteria could apply)

E.5 End points

E.5.1

Primary end point(s)

1) OR according to RECIST 1.1
assessed by IRC

2) OS

E.5.1.1

Timepoint(s) of evaluation of this end point

Time from randomization to
planned final assessment

E.5.2

Secondary end point(s)

2) OR according to RECIST 1.1 assessed by IRC
3) DOR assessed from CR or PR according to RECIST 1.1 assessed by IRC
until PD, death, or last tumor assessment
4) PK profile of M7824 in terms of Ceoi
5 PK profile of M7824 in terms of
Ctrough
6) Immunogenicity as measured by ADA assays at Baseline and
ontreatment

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Time from random. to the last 12-week safety follow-up visit, expected at 47 months.
2) From random. to assessment when 200 OS events occur, OS PA exp. at 49 months from first participant in the study
3) Time from random. to planned final assessment for unconfirmed BOR, exp.
26 months.
4) Time from random. to final assessm.PFS after 192 events at 37 months.
5) Time from CR or PR to planned assessment after 192 PFS events, expected at 37 months.
6,7) Predose samples at Weeks 1,3,5,7, then 6 weekly during treatment; postdose (within 30 min) samples at 6 weekly during treatment and
up to study’s Safety Follow-up Visit at 28 days after last study intervention administ.
8) From random. up to study’s Safety Folup Visit, defined as 28 days after last study intervention administr.

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

Yes

E.8.1.7.1

Other trial design description

adaptive design

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

Australia

Canada

Japan

United States

European Union

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

The end of the study is defined as the data cut off date for the primary
OS analysis when the planned number of deaths had been reported.

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

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:

292

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

292

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

340

F.4.2.2

In the whole clinical trial

584

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)

After a participant has completed the study or has withdrawn early, participants may receive the care they and their physicians agree upon. Participants will be followed for survival and AEs as specified in the 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

2018-09-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-11-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-06-25

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