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Clinical Trial Results:
Randomized Clinical Trial of Maintenance Therapy with Immunomodulator MGN1703 in Patients with Extensive Disease Small Cell Lung Cancer after Platinum-Based First-Line Therapy

Summary
EudraCT number	2013-003503-19
Trial protocol	BE AT DE ES
Global end of trial date	05 Oct 2017

Results information
Results version number	v1(current)
This version publication date	06 Jan 2019
First version publication date	06 Jan 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

MGN1703-C03

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

MOLOGEN AG

Sponsor organisation address

Fabeckstraße 30, Berlin, Germany,

Public contact

Corporate Communications , Mologen AG, 49 0308417880, info@mologen.com

Scientific contact

Clinical Development , Mologen AG, 49 0308417880, info@mologen.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

05 Oct 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Oct 2017

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy and safety of lefitolimod, administered as above, as a switch maintenance treatment for patients with extensive-stage SCLC who achieved at least partial response following platinum-based first-line chemotherapy.

Protection of trial subjects

The investigators and all parties involved in this study conducted the study in adherence to the ethical principles based on the Declaration of Helsinki, GCP, ICH guidelines, and the applicable national and local laws and regulatory requirements. Participation in this study was strictly voluntary. All patients had the right to withdraw from the study at any time, for any reason, and without penalty or loss of benefits to which the patient is otherwise entitled. Only investigators qualified by education, training and experience were selected to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Mar 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 32

Country: Number of subjects enrolled

Austria: 1

Country: Number of subjects enrolled

Belgium: 8

Country: Number of subjects enrolled

Germany: 62

Worldwide total number of subjects

103

EEA total number of subjects

103

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Patients with ES-SCLC and objective tumor response (as per RECIST 1.1) following 4 cycles of platinum-based first-line induction therapy

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Lefitolimod maintenance therapy

Arm description

According to the investigator's judgement, patients either (i) terminated platinum-based chemotherapy or (ii) received a fifth and possibly a sixth cycle of platinum-based chemotherapy. In either case they also received lefitolimod twice a week, administered subcutaneously at two application sites at a dose level of 60 mg.

Arm type

Experimental

Investigational medicinal product name

Lefitolimod

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

60 mg/4 mL (15 mg/mL) solution, 2 mL administered at 2 application sites (total dose 60 mg) Twice weekly until disease progression or any other reason to interrupt or discontinue study treatment

Control arm

Arm description

According to the investigator's judgement, patients either (i) terminated platinum-based chemotherapy or (ii) received a fifth and possibly a sixth cycle of platinum-based chemotherapy. In either case this was followed by further treatment according to the local standard of care.

Arm type

Standard of care

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 1	Lefitolimod maintenance therapy	Control arm
Started	62	41
Completed	62	34
Not completed	0	7
Consent withdrawn by subject	-	5
Lost to follow-up	-	2

Baseline characteristics

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Reporting group title

Overall Trial

Reporting group description

Reporting group values	Overall Trial	Total
Number of subjects	103	103
Age categorical
Male and female patients ≥ 18 years of age
Units: Subjects
Adults (18-64 years)	57	57
From 65-84 years	46	46
Age continuous
Units: years
median (full range (min-max))	63 (49 to 82)	-
Gender categorical
Units: Subjects
Male	69	69
Female	34	34

Subject analysis set title

FAS

Subject analysis set type

Full analysis

Subject analysis set description

All patients randomized into the trial

Subject analysis sets values	FAS
Number of subjects	103
Age categorical
Male and female patients ≥ 18 years of age
Units: Subjects
Adults (18-64 years)	57
From 65-84 years	46
Age continuous
Units: years
median (full range (min-max))	63 (49 to 82)
Gender categorical
Units: Subjects
Male	69
Female	34

End points

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Reporting group title

Lefitolimod maintenance therapy

Reporting group description

Reporting group title

Control arm

Reporting group description

According to the investigator's judgement, patients either (i) terminated platinum-based chemotherapy or (ii) received a fifth and possibly a sixth cycle of platinum-based chemotherapy. In either case this was followed by further treatment according to the local standard of care.

Subject analysis set title

FAS

Subject analysis set type

Full analysis

Subject analysis set description

All patients randomized into the trial

Primary: Overall survival

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End point title

Overall survival

End point description

End point type

Primary

End point timeframe

Two years from the date of randomization

End point values	Lefitolimod maintenance therapy	Control arm	FAS
Number of subjects analysed	62	41	103
Units: Events	55	32	87

Final analysis

Comparison groups

Control arm v Lefitolimod maintenance therapy

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.98

Method

Logrank

Parameter type

Hazard ratio (HR)

Confidence interval

level

95%

sides

1-sided

lower limit

0.73

upper limit

1.76

Adverse events

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Timeframe for reporting adverse events

Adverse event data were collected after signing the informed consent until 30 days after end of study treatment

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

Control arm: control arm

Reporting group description

According to the investigator's judgement, patients either (i) terminated platinum-based chemotherapy or (ii) received a fifth and possibly a sixth cycle of platinum-based chemotherapy. In either case this was followed by further treatment according to the local standard of care.

Reporting group title

Experimental arm: lefitolimod maintenance therapy

Reporting group description

Serious adverse events	Control arm: control arm	Experimental arm: lefitolimod maintenance therapy
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 39 (0.00%)	20 / 61 (32.79%)
number of deaths (all causes)	32	54
number of deaths resulting from adverse events	0	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Vascular disorders
Hypotension
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Superior vena cava syndrome
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
General physical health deterioration
subjects affected / exposed	0 / 39 (0.00%)	3 / 61 (4.92%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Pain
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 39 (0.00%)	3 / 61 (4.92%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hemiparesis
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Leukoencephalopathy
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 39 (0.00%)	2 / 61 (3.28%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Diplopia
subjects affected / exposed	0 / 39 (0.00%)	2 / 61 (3.28%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Eye pain
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
alternative assessment type: Systematic
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Urine abnormality
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Inappropriate antidiuretic hormone secretion
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Infection
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic infection
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyponatraemia
subjects affected / exposed	0 / 39 (0.00%)	1 / 61 (1.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Control arm: control arm	Experimental arm: lefitolimod maintenance therapy
Total subjects affected by non serious adverse events
subjects affected / exposed	35 / 39 (89.74%)	58 / 61 (95.08%)
Vascular disorders
Hypertension
subjects affected / exposed	2 / 39 (5.13%)	0 / 61 (0.00%)
occurrences all number	3	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	7 / 39 (17.95%)	8 / 61 (13.11%)
occurrences all number	12	11
Chest pain
subjects affected / exposed	4 / 39 (10.26%)	3 / 61 (4.92%)
occurrences all number	5	3
Fatigue
subjects affected / exposed	3 / 39 (7.69%)	11 / 61 (18.03%)
occurrences all number	3	16
Injection site erythema
subjects affected / exposed	0 / 39 (0.00%)	4 / 61 (6.56%)
occurrences all number	0	4
Injection site reaction
subjects affected / exposed	0 / 39 (0.00%)	5 / 61 (8.20%)
occurrences all number	0	10
Pyrexia
subjects affected / exposed	0 / 39 (0.00%)	7 / 61 (11.48%)
occurrences all number	0	8
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 39 (7.69%)	14 / 61 (22.95%)
occurrences all number	3	14
Dysphonia
subjects affected / exposed	1 / 39 (2.56%)	4 / 61 (6.56%)
occurrences all number	1	5
Dyspnoea
subjects affected / exposed	4 / 39 (10.26%)	8 / 61 (13.11%)
occurrences all number	4	8
Rales
subjects affected / exposed	2 / 39 (5.13%)	0 / 61 (0.00%)
occurrences all number	2	0
Investigations
Platelet count decreased
subjects affected / exposed	0 / 39 (0.00%)	4 / 61 (6.56%)
occurrences all number	0	5
Injury, poisoning and procedural complications
Radiation skin injury
subjects affected / exposed	2 / 39 (5.13%)	0 / 61 (0.00%)
occurrences all number	2	0
Nervous system disorders
Dizziness
subjects affected / exposed	5 / 39 (12.82%)	3 / 61 (4.92%)
occurrences all number	5	3
Headache
subjects affected / exposed	2 / 39 (5.13%)	12 / 61 (19.67%)
occurrences all number	2	19
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 39 (5.13%)	7 / 61 (11.48%)
occurrences all number	2	7
Leukopenia
subjects affected / exposed	1 / 39 (2.56%)	4 / 61 (6.56%)
occurrences all number	1	5
Neutropenia
subjects affected / exposed	2 / 39 (5.13%)	8 / 61 (13.11%)
occurrences all number	2	11
Thrombocytopenia
subjects affected / exposed	0 / 39 (0.00%)	4 / 61 (6.56%)
occurrences all number	0	5
Ear and labyrinth disorders
Hypoacusis
subjects affected / exposed	3 / 39 (7.69%)	1 / 61 (1.64%)
occurrences all number	3	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 39 (5.13%)	4 / 61 (6.56%)
occurrences all number	2	5
Constipation
subjects affected / exposed	1 / 39 (2.56%)	7 / 61 (11.48%)
occurrences all number	1	7
Diarrhoea
subjects affected / exposed	1 / 39 (2.56%)	5 / 61 (8.20%)
occurrences all number	1	6
Nausea
subjects affected / exposed	8 / 39 (20.51%)	8 / 61 (13.11%)
occurrences all number	10	8
Odynophagia
subjects affected / exposed	2 / 39 (5.13%)	1 / 61 (1.64%)
occurrences all number	2	1
Vomiting
subjects affected / exposed	1 / 39 (2.56%)	5 / 61 (8.20%)
occurrences all number	1	6
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	0 / 39 (0.00%)	10 / 61 (16.39%)
occurrences all number	0	33
Pruritus
subjects affected / exposed	1 / 39 (2.56%)	4 / 61 (6.56%)
occurrences all number	1	6
Rash
subjects affected / exposed	0 / 39 (0.00%)	4 / 61 (6.56%)
occurrences all number	0	19
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	5 / 39 (12.82%)	8 / 61 (13.11%)
occurrences all number	5	10
Pain in extremity
subjects affected / exposed	1 / 39 (2.56%)	5 / 61 (8.20%)
occurrences all number	1	5
Infections and infestations
Nasopharyngitis
subjects affected / exposed	0 / 39 (0.00%)	4 / 61 (6.56%)
occurrences all number	0	5
Respiratory tract infection
subjects affected / exposed	0 / 39 (0.00%)	4 / 61 (6.56%)
occurrences all number	0	7
Urinary tract infection
subjects affected / exposed	0 / 39 (0.00%)	4 / 61 (6.56%)
occurrences all number	0	4
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	5 / 39 (12.82%)	6 / 61 (9.84%)
occurrences all number	5	8

More information

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Were there any global substantial amendments to the protocol? Yes

20 Mar 2014

Changes to in- and exclusion criteria Changes to medication and other treatment Changes to study procedures Administrative changes

04 Dec 2014

Changes to introduction Changes to in- and exclusion criteria Change to numbers of subjects and study centers involved Changes to description of data safety monitoring committee Changes to assessments Changes to insurance statement Changes to treatment schedule Administrative changes

22 Sep 2015

Changes to in- and exclusion criteria Changes to adverse event reporting Changes to concomitant medication Changes to assessments Administrative changes

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
Randomized Clinical Trial of Maintenance Therapy with Immunomodulator MGN1703 in Patients with Extensive Disease Small Cell Lung Cancer after Platinum-Based First-Line Therapy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall survival

Primary: Overall survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: Randomized Clinical Trial of Maintenance Therapy with Immunomodulator MGN1703 in Patients with Extensive Disease Small Cell Lung Cancer after Platinum-Based First-Line Therapy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall survival

Primary: Overall survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Randomized Clinical Trial of Maintenance Therapy with Immunomodulator MGN1703 in Patients with Extensive Disease Small Cell Lung Cancer after Platinum-Based First-Line Therapy