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Clinical Trial Results:
A Phase IIb/III randomised, double-blind, placebo-controlled study comparing first-line therapy with or without TG4010 immunotherapy product in patients with stage IV non-small cell lung cancer (NSCLC).

Summary
EudraCT number	2011-001468-23
Trial protocol	BE HU GB DE ES PL IT
Global end of trial date	06 Jul 2015

Results information
Results version number	v1(current)
This version publication date	20 Jul 2017
First version publication date	20 Jul 2017
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

TG4010.14

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Transgene S.A.

Sponsor organisation address

400, Boulevard Gonthier d'Andernach,Parc d’Innovation - CS80166, Illkirch Graffenstaden Cedex, France, 67405

Public contact

Transgene Medical Affairs, Transgene S.A., clinical.trials@transgene.fr

Scientific contact

Transgene Medical Affairs, Transgene S.A., clinical.trials@transgene.fr

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

06 Jul 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

15 Dec 2014

Global end of trial reached?

Yes

Global end of trial date

06 Jul 2015

Was the trial ended prematurely?

Yes

Main objective of the trial

Phase IIb part: to prospectively validate the level of Triple Positive Activated Lymphocytes (TrPAL), as a predictive biomarker of TG4010’s activity by comparing Progression-Free Survival (PFS) between the TG4010 arm (TG4010 + first-line therapy) and the placebo arm (placebo + first-line therapy) in the 2 subgroups of subjects according to their level of TrPAL before randomisation (normal and high level of TrPAL). Phase III part: To demonstrate that TG4010 improves overall survival (OS) as compared to placebo in stage IV NSCLC patients with non-squamous tumour histology receiving first-line chemotherapy.

Protection of trial subjects

This study was conducted in accordance with the updated Declaration of Helsinki adopted by the World Medical Association, in compliance with the approved protocol and its amendments, the International Council for Harmonisation good clinical practice, and national regulatory requirements in the participating countries.

Background therapy

Chemotherapy was given as 21-day cycles starting from Day 1 of Cycle 1 for a minimum of 4 cycles and up to 6 cycles. The platinum doublet chemotherapy regimen administered was determined by histology and at Investigator discretion as follows: • Non-squamous cell: Paclitaxel (200 milligrams/square metre [mg/m²]) and carboplatin (target area under the curve [AUC] 6.0) on Day 1 of each cycle with the next course of chemotherapy on Day 22; OR pemetrexed (500 mg/m²) and cisplatin (75 mg/m²) on Day 1 of each cycle with the next course of chemotherapy on Day 22 • Squamous cell: Paclitaxel (200 mg/m²) and carboplatin (AUC 6.0) on Day 1 of each cycle with the next course of chemotherapy on Day 22; OR gemcitabine (1250 mg/m²) on Day 1 and Day 8 of each cycle and cisplatin (75 mg/m²) on Day 1 of each cycle with the next course of chemotherapy on Day 22. Bevacizumab was allowed for patients with non-squamous carcinoma (if initiated at the same time as chemotherapy) and was administered at a dose of 7.5 or 15 mg/kilogram (kg) according to country-specific approved labelling or prescribing information. Bevacizumab treatment was given on Day 1 of each cycle (starting from Day 1 of Cycle 1) until disease progression or premature discontinuation due to any reason. Pemetrexed (for non-squamous carcinoma) or erlotinib (whatever the histology) were to be given as maintenance therapy in eligible patients who have not progressed after 4 to 6 cycles of chemotherapy (according to labeling in each country) unless they received bevacizumab as part of first-line therapy. Pemetrexed (at the dose of 500 mg/m² every 3 weeks, given on the same day as TG4010/placebo) or erlotinib (at the dose of 150 mg daily) were administered in combination with TG4010/placebo until disease progression or premature discontinuation due to any reason.

Evidence for comparator

Actual start date of recruitment

10 Apr 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Israel: 3

Country: Number of subjects enrolled

United States: 9

Country: Number of subjects enrolled

Poland: 22

Country: Number of subjects enrolled

Spain: 20

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

Belgium: 24

Country: Number of subjects enrolled

France: 90

Country: Number of subjects enrolled

Hungary: 41

Country: Number of subjects enrolled

Italy: 3

Worldwide total number of subjects

222

EEA total number of subjects

210

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)

143

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study consisted of a Phase IIb and a Phase III part. 222 subjects were randomised into the Phase IIb part in a 1:1 ratio of TG4010 to placebo. The cut-off date for primary analysis of PFS was 15 December 2014 and OS cut off date was 6 July 2015. The study was prematurely terminated after completion of Phase IIb and Phase III did not proceed.

Screening details

The level of TrPAL (percentage of triple positive CD16+ CD56+ CD69+ cells among the total lymphocyte population) was evaluated before randomisation. For the phase IIb part, subjects were categorised in 1 of the 2 groups (normal and high TrPAL) by using a cut-off value determined in adult healthy donors as being the upper limit of normal (ULN).

Period 1 title

Phase IIb Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer

Blinding implementation details

The monitors, data managers, investigators and subjects remained blinded to drug identity until the date of the last final analysis of the Phase IIb. The statistician was unblinded for all subjects at the time of final analysis in subjects with normal TrPAL. The sponsor was unblinded for the treatment code firstly for subjects with normal TrPAL at the time of the final analysis in this subgroup and secondly for subjects with high TrPAL at the time of the final analysis in this subgroup.

Are arms mutually exclusive

Yes

TG4010

Arm description

Subjects received TG4010 plus chemotherapy as first-line treatment followed by TG4010 plus maintenance therapy if appropriate. TG4010 was administered on Day 1 of Cycle 1 of chemotherapy and then weekly for 6 weeks by subcutaneous (SC) injections, then once every 3 weeks until disease progression or premature discontinuation. Chemotherapy was given as 21-day cycles for a minimum of 4 cycles and up to 6 cycles. If prescribed, bevacizumab was continued in combination with TG4010 and administered every 3 weeks until disease progression, premature discontinuation, or toxicity.

Arm type

Experimental

Investigational medicinal product name

TG4010

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TG4010 is a suspension of recombinant modified Vaccinia virus strain Ankara (MVA) carrying coding sequences for human Mucin 1 (MUC1) antigen and human interleukin-2 in the diluent named TG0008. TG4010 was administered at a dose of 1 x 10^8 plaque-forming unit (pfu) (corresponding to 0.5 millilitre [mL] of TG4010) once every week for 6 weeks, starting on Day 1 of Cycle 1, and then every 3 weeks thereafter until disease progression or premature discontinuation due to any reason. Each SC injection was performed in a single site. Four injection sites were used successively (left and right arm, left and right thigh) according to a rotation schedule.

Placebo

Arm description

Subjects received placebo plus chemotherapy as first-line treatment followed by placebo plus maintenance therapy if appropriate. Placebo was administered on Day 1 of Cycle 1 of chemotherapy and then weekly for 6 weeks by SC injections, then once every 3 weeks until disease progression or premature discontinuation. Chemotherapy was given as 21-day cycles for a minimum of 4 cycles and up to 6 cycles. If prescribed, bevacizumab was continued in combination with placebo and administered every 3 weeks until disease progression, premature discontinuation, or toxicity.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

TG0008

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

The placebo used in this study was the diluent of TG4010 (TG0008) and was administered as a single SC injection in a volume of 0.5 mL. Placebo was administered once every week for 6 weeks, starting on Day 1 of Cycle 1, and then every 3 weeks thereafter until disease progression or premature discontinuation due to any reason. Four injection sites were used successively (left and right arm, left and right thigh) according to a rotation schedule.

Number of subjects in period 1	TG4010	Placebo
Started	111	111
Completed	105	98
Not completed	6	13
Consent withdrawn by subject	4	7
Investigator's Decision	2	2
Administrative problems	-	1
Lost to follow-up	-	3

Baseline characteristics

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Reporting group title

TG4010

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	TG4010	Placebo	Total
Number of subjects	111	111	222
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	66	77	143
From 65-84 years	45	34	79
85 years and over	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	62.8 ( 8.5 )	59.5 ( 8.8 )	-
Gender categorical
Units: Subjects
Female	39	41	80
Male	72	70	142
Histology
Units: Subjects
Adenocarcinoma	95	90	185
Squamous cell carcinoma	13	13	26
Large cell carcinoma	2	3	5
Undifferentiated carcinoma	0	3	3
Other	1	2	3
Performance status (PS)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Units: Subjects
PS=0	33	35	68
PS=1	77	76	153
Missing	1	0	1
Smoking Status
Units: Subjects
Never smoked	7	12	19
Current or ex-smoker	104	99	203
TrPAL Level based on ULN cut-off value
Units: Subjects
≤ ULN (normal)	85	85	170
>ULN (high)	26	26	52
TrPAL level based on Third quartile (Q3) cut-off value
Units: Subjects
≤ Q3 (non-elevated)	71	76	147
> Q3 (elevated)	40	35	75

End points

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Reporting group title

TG4010

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

TG4010: Normal TrPAL Subgroup

Subject analysis set type

Sub-group analysis

Subject analysis set description

Analyses were performed independently in each group of subjects according to their level of TrPAL before randomisation, based on a predetermined ULN cut-off. Of 111 subjects randomised to the TG4010 arm, 85 were categorised with a level of TrPAL less than or equal to the ULN (normal TrPAL).

Subject analysis set title

Placebo: Normal TrPAL Subgroup

Subject analysis set type

Sub-group analysis

Subject analysis set description

Analyses were performed independently in each group of subjects according to their level of TrPAL before randomisation, based on a predetermined ULN cut-off. Of 111 subjects randomised to the placebo arm, 85 were categorised with a level of TrPAL less than or equal to the ULN (normal TrPAL).

Subject analysis set title

TG4010: High TrPAL Subgroup

Subject analysis set type

Sub-group analysis

Subject analysis set description

Analyses were performed independently in each group of subjects according to their level of TrPAL before randomisation, based on a predetermined ULN cut-off. Of 111 subjects randomised to the TG4010 arm, 26 were categorised with a level of TrPAL greater than the ULN (high TrPAL).

Subject analysis set title

Placebo: High TrPAL Subgroup

Subject analysis set type

Sub-group analysis

Subject analysis set description

Analyses were performed independently in each group of subjects according to their level of TrPAL before randomisation, based on a predetermined ULN cut-off. Of 111 subjects randomised to the placebo arm, 26 were categorised with a level of TrPAL greater than the ULN (high TrPAL).

Subject analysis set title

TG4010: Non-elevated TrPAL Subgroup

Subject analysis set type

Sub-group analysis

Subject analysis set description

By using a quartile approach for categorisation, subjects with less than or equal to Q3 cut-off value for TrPAL at baseline were categorised into the non-elevated TrPAL subgroup. Of 111 subjects randomised to the TG4010 arm, 71 were categorised with non-elevated TrPAL levels.

Subject analysis set title

Placebo: Non-elevated TrPAL Subgroup

Subject analysis set type

Sub-group analysis

Subject analysis set description

By using a quartile approach for categorisation, subjects with less than or equal to Q3 cut-off value for TrPAL at baseline were categorised into the non-elevated TrPAL subgroup. Of 111 subjects randomised to the placebo arm, 76 were categorised with non-elevated TrPAL levels.

Subject analysis set title

TG4010: Elevated TrPAL Subgroup

Subject analysis set type

Sub-group analysis

Subject analysis set description

By using a quartile approach for categorisation, subjects with greater than the Q3 cut-off value for TrPAL at baseline were categorised into the elevated TrPal subgroup. Of 111 subjects randomised to the TG4010 arm, 40 were categorised with elevated TrPAL levels.

Subject analysis set title

Placebo: Elevated TrPal Subgroup

Subject analysis set type

Sub-group analysis

Subject analysis set description

By using a quartile approach for categorisation, subjects with greater than the Q3 cut-off value for TrPAL at baseline were categorised into the non-elevated TrPal subgroup. Of 111 subjects randomised to the placebo arm, 35 were categorised with elevated TrPAL levels.

Primary: Comparison of PFS Events in Subjects Treated with TG4010 or Placebo.

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End point title

Comparison of PFS Events in Subjects Treated with TG4010 or Placebo.

End point description

The primary analysis of PFS was performed in the 2 groups of subjects defined by their level of TrPAL at baseline (≤ ULN [normal] or > ULN [high]). This analysis was repeated in the 2 groups of subjects defined by the quartile approach, non-elevated (corresponding to ≤ Q3) and elevated (corresponding to >Q3) TrPAL levels. PFS events were recorded from the date of randomisation to the date of first documented tumour progression or death due to any cause, whichever occurred first. PFS was censored if no progression or death was observed at the cut-off date for analysis, or at the date when a further antineoplastic therapy was started. Determination of progression was based on local evaluations of baseline and post-baseline scans and by evaluation of target and non-target disease according to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1.

End point type

Primary

End point timeframe

Tumour progression was evaluated every 6 weeks until documented progression or for a period of 9 months. Beyond 9 months, evaluations were performed every 12 weeks until documented disease progression. Up to a maximum of 140 weeks (until cut-off date).

End point values	TG4010: Normal TrPAL Subgroup	Placebo: Normal TrPAL Subgroup	TG4010: High TrPAL Subgroup	Placebo: High TrPAL Subgroup	TG4010: Non-elevated TrPAL Subgroup	Placebo: Non-elevated TrPAL Subgroup	TG4010: Elevated TrPAL Subgroup	Placebo: Elevated TrPal Subgroup
Number of subjects analysed	85	85	26	26	71	76	40	35
Units: Events	76	75	21	22	62	67	35	30

Bayesian analysis: Normal TrPAL subgroup

Statistical analysis description

A Bayesian analysis was performed to prospectively validate the level of TrPAL as a predictive biomarker of TG4010’s activity. After 89 PFS events had been observed in the normal TrPAL subgroup, the null hypothesis H0: HR ≥ 1 was tested against the alternative hypothesis HA: HR < 1, where HR is the PFS hazard ratio for first-line therapy plus TG4010 (TG4010 arm) relative to first-line therapy plus placebo (placebo arm).

Comparison groups

TG4010: Normal TrPAL Subgroup v Placebo: Normal TrPAL Subgroup

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.016 ^[2]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.03

Notes
[1] - The null hypothesis H0: HR ≥ 1 was tested against the alternative hypothesis HA: HR < 1, where HR is the PFS hazard ratio for first-line therapy+TG4010 (TG4010 arm) relative to first-line therapy+placebo (placebo arm). The hypothesis was tested by using the posterior distribution of an estimator of the log HR.
[2] - Efficacy criteria: 1- P (HR < 1 / observed data) <=0.05

Bayesian analysis: High TrPAL subgroup

Statistical analysis description

A Bayesian analysis was performed to prospectively validate the level of TrPAL as a predictive biomarker of TG4010’s activity. After 38 PFS events had been observed in the high TrPAL subgroup, the null hypothesis H0: HR ≤ 1 was tested against the alternative hypothesis HA: HR > 1, where HR was the PFS hazard ratio for first-line therapy plus TG4010 relative to first-line therapy plus placebo.

Comparison groups

TG4010: High TrPAL Subgroup v Placebo: High TrPAL Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0.687 ^[4]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.4

Notes
[3] - The null hypothesis H0: HR ≤ 1 was tested against the alternative hypothesis HA: HR ≥ 1, where HR is the PFS hazard ratio for first-line therapy+TG4010 (TG4010 arm) relative to first-line therapy+placebo (placebo arm). The hypothesis was tested by using the posterior distribution of an estimator of the log HR.
[4] - Efficacy criteria: 1-P (HR >1 / observed data) <= 0.20

Bayesian analysis: Non-elevated TrPAL subgroup

Statistical analysis description

A Bayesian analysis was performed to prospectively validate the level of TrPAL as a predictive biomarker of TG4010’s activity. After 89 PFS events had been observed in the non elevated TrPAL subgroup, the null hypothesis H0: HR ≥ 1 was tested against the alternative hypothesis HA: HR < 1, where HR is the PFS hazard ratio for first-line therapy plus TG4010 (TG4010 arm) relative to first-line therapy plus placebo (placebo arm).

Comparison groups

TG4010: Non-elevated TrPAL Subgroup v Placebo: Non-elevated TrPAL Subgroup

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.005 ^[6]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

0.96

Notes
[5] - The null hypothesis H0: HR ≥ 1 was tested against the alternative hypothesis HA: HR < 1, where HR is the PFS hazard ratio for first-line therapy+TG4010 (TG4010 arm) relative to first-line therapy+placebo (placebo arm). The hypothesis was tested by using the posterior distribution of an estimator of the log HR.
[6] - Efficacy criteria: 1- P (HR < 1 / observed data) <=0.05

Bayesian analysis: Elevated TrPAL subgroup

Statistical analysis description

Comparison groups

Placebo: Elevated TrPal Subgroup v TG4010: Elevated TrPAL Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

= 0.553 ^[8]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.47

Notes
[7] - The null hypothesis H0: HR ≤ 1 was tested against the alternative hypothesis HA: HR ≥ 1, where HR is the PFS hazard ratio for first-line therapy+TG4010 (TG4010 arm) relative to first-line therapy+placebo (placebo arm). The hypothesis was tested by using the posterior distribution of an estimator of the log HR.
[8] - Efficacy criteria: 1-P (HR >1 / observed data) <= 0.20

Frequentist analysis: Normal TrPAL subgroup

Statistical analysis description

As a supportive analysis, a frequentist analysis was also performed to compare PFS between the 2 study arms in each TrPAL subgroup by using a one-sided non-stratified log rank test.

Comparison groups

TG4010: Normal TrPAL Subgroup v Placebo: Normal TrPAL Subgroup

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

other ^[9]

P-value

= 0.032

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.02

Notes
[9] - Hazard ratio and corresponding 95% confidence intervals (CIs) were derived using the Cox proportional hazards model.

Frequentist analysis: High TrPAL subgroup

Statistical analysis description

As a supportive analysis, a frequentist analysis was also performed to compare PFS between the 2 study arms in each TrPAL subgroup by using a one-sided non-stratified log rank test.

Comparison groups

TG4010: High TrPAL Subgroup v Placebo: High TrPAL Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[10]

P-value

= 0.195

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.4

Notes
[10] - Hazard ratio and corresponding 95% CIs were derived using the Cox proportional hazards model.

Frequentist analysis: Non-elevated TrPAL subgroup

Statistical analysis description

As a supportive analysis, a frequentist analysis was also performed to compare PFS between the 2 study arms in each TrPAL subgroup by using a one-sided non-stratified log rank test.

Comparison groups

TG4010: Non-elevated TrPAL Subgroup v Placebo: Non-elevated TrPAL Subgroup

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other ^[11]

P-value

= 0.01

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

0.94

Notes
[11] - Hazard ratio and corresponding 95% CIs were derived using the Cox proportional hazards model.

Frequentist analysis: Elevated TrPAL subgroup

Statistical analysis description

As a supportive analysis, a frequentist analysis was also performed to compare PFS between the 2 study arms in each TrPAL subgroup by using a one-sided non-stratified log rank test.

Comparison groups

TG4010: Elevated TrPAL Subgroup v Placebo: Elevated TrPal Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[12]

P-value

= 0.343

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.48

Notes
[12] - Hazard ratio and corresponding 95% CIs were derived using the Cox proportional hazards model.

Secondary: Comparison of OS Events in Subjects Treated with TG4010 or Placebo.

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End point title

Comparison of OS Events in Subjects Treated with TG4010 or Placebo.

End point description

OS was defined as the time from the date of randomisation to the date of death due to any cause. Analysis of OS was conducted when at least 70% of subjects had died. The number of deaths at the cut-off date for OS was recorded for the whole population and in each TrPAL subgroup. If a subject was not known to have died, survival was censored at the date of last contact.

End point type

Secondary

End point timeframe

Subjects were followed for survival every 3 months up to a maximum of 169 weeks (until cut-off date for OS analysis).

End point values	TG4010	Placebo	TG4010: Normal TrPAL Subgroup	Placebo: Normal TrPAL Subgroup	TG4010: High TrPAL Subgroup	Placebo: High TrPAL Subgroup	TG4010: Non-elevated TrPAL Subgroup	Placebo: Non-elevated TrPAL Subgroup	TG4010: Elevated TrPAL Subgroup	Placebo: Elevated TrPal Subgroup
Number of subjects analysed	111	111	85	85	26	26	71	76	40	35
Units: Events (Deaths)	78	87	58	69	20	18	47	62	31	25

Comparison of OS in Whole Population

Statistical analysis description

The distribution of OS was compared between the treatment arms using a one-sided non-stratified log-rank test. Hazard ratio and corresponding 95% CIs were derived using the Cox proportional hazards model.

Comparison groups

TG4010 v Placebo

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.055

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.06

Comparison of OS in Normal TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: Normal TrPAL Subgroup v Placebo: Normal TrPAL Subgroup

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.052

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.06

Comparison of OS in High TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: High TrPAL Subgroup v Placebo: High TrPAL Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.362

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.7

Comparison of OS in Non-elevated TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: Non-elevated TrPAL Subgroup v Placebo: Non-elevated TrPAL Subgroup

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.018

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

0.98

Comparison of OS in Elevated TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: Elevated TrPAL Subgroup v Placebo: Elevated TrPal Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.444

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.76

Secondary: Median OS in Subjects Treated with TG4010 or Placebo.

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End point title

Median OS in Subjects Treated with TG4010 or Placebo.

End point description

OS was defined as the time from the date of randomisation to the date of death due to any cause. Analysis of OS was conducted when at least 70 % of subjects had died for the whole population and in each TrPAL group. If a subject is not known to have died, survival was censored at the date of last contact.

End point type

Secondary

End point timeframe

Subjects were followed for survival every 3 months up to a maximum of 169 weeks (until cut-off date for OS analysis).

End point values	TG4010	Placebo	TG4010: Normal TrPAL Subgroup	Placebo: Normal TrPAL Subgroup	TG4010: High TrPAL Subgroup	Placebo: High TrPAL Subgroup	TG4010: Non-elevated TrPAL Subgroup	Placebo: Non-elevated TrPAL Subgroup	TG4010: Elevated TrPAL Subgroup	Placebo: Elevated TrPal Subgroup
Number of subjects analysed	111	111	85	85	26	26	71	76	40	35
Units: Months
median (confidence interval 95%)	12.7 (9.8 to 16.4)	10.5 (9.5 to 14.3)	12.6 (9.7 to 15.6)	10.5 (8.9 to 14.3)	14.2 (7.1 to 22.4)	10.9 (7.7 to 21.7)	13 (9.7 to 18.4)	10.4 (8.2 to 14.1)	12.4 (7.3 to 17)	13.7 (8.8 to 21)

No statistical analyses for this end point

Secondary: Comparison of Overall Response Rate (ORR) in Subjects Treated with TG4010 or Placebo.

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End point title

Comparison of Overall Response Rate (ORR) in Subjects Treated with TG4010 or Placebo.

End point description

ORR was defined as the percentage of subjects whose best overall response to tumour evaluation was either complete response (CR) or partial response (PR) confirmed at least 4 weeks after initial documentation. Objective response rate was the percentage of subjects whose best overall response is either CR or PR according to RECIST version 1.1. Results are presented by treatment arm and by TrPAL subgroup for objective response rate and also percentage of subjects with best overall response (CR, PR, stable disease and progressive disease).

End point type

Secondary

End point timeframe

Tumour response was evaluated every 6 weeks until documented progression or for a period of 9 months. Beyond 9 months, evaluations were performed every 12 weeks until documented disease progression. Up to a maximum of 140 weeks (until cut-off date).

End point values	TG4010	Placebo	TG4010: Normal TrPAL Subgroup	Placebo: Normal TrPAL Subgroup	TG4010: High TrPAL Subgroup	Placebo: High TrPAL Subgroup	TG4010: Non-elevated TrPAL Subgroup	Placebo: Non-elevated TrPAL Subgroup	TG4010: Elevated TrPAL Subgroup	Placebo: Elevated TrPal Subgroup
Number of subjects analysed	111	111	85	85	26	26	71	76	40	35
Units: Percentage of Subjects
number (not applicable)
Objective Response Rate	39.6	28.8	38.8	30.6	42.3	23.1	39.4	31.6	40	22.9
CR	0.9	0	0	0	3.8	0	0	0	2.5	0
PR	38.7	28.8	38.8	30.6	38.5	23.1	39.4	31.6	37.5	22.9
Stable Disease	44.1	48.6	44.7	48.2	42.3	50	45.1	46.1	42.5	54.3
Progressive Disease	11.7	13.5	12.9	12.9	7.7	15.4	11.3	14.5	12.5	11.4
Unknown	4.5	9	3.5	8.2	7.7	11.5	4.2	7.9	5	11.4

Comparison of ORR in Whole Population

Statistical analysis description

The Cochran-Mantel-Haenszel chi-square test stratified by tumour histology, bevacizumab administration, chemotherapy regimen, and performance status was used to compare the 2 treatment arms with respect to the ORR at one-sided 2.5% level of significance.

Comparison groups

TG4010 v Placebo

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.03

Method

Cochran-Mantel-Haenszel

Confidence interval

Comparison of ORR in Normal TrPAl Subgroup

Statistical analysis description

Comparison groups

TG4010: Normal TrPAL Subgroup v Placebo: Normal TrPAL Subgroup

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.088

Method

Cochran-Mantel-Haenszel

Confidence interval

Comparison of ORR in High TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: High TrPAL Subgroup v Placebo: High TrPAL Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.092

Method

Cochran-Mantel-Haenszel

Confidence interval

Comparison of ORR in Non-elevated TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: Non-elevated TrPAL Subgroup v Placebo: Non-elevated TrPAL Subgroup

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.079

Method

Cochran-Mantel-Haenszel

Confidence interval

Comparison of ORR in Elevated TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: Elevated TrPAL Subgroup v Placebo: Elevated TrPal Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.06

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Comparison of Percentage of Subjects with a 9 Month Time to Overall Response (TOR) in Subjects Treated with TG4010 or Placebo.

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End point title

Comparison of Percentage of Subjects with a 9 Month Time to Overall Response (TOR) in Subjects Treated with TG4010 or Placebo.

End point description

TOR events were recorded from the time between date of randomisation to the date of first documented response (CR or PR). TOR was censored if no progression or death was observed at the cut-off date for analysis, or at the date when a further antineoplastic therapy was started. A Kaplan-Meier curve was constructed for each treatment arm and subgroup. The percentage of subjects with a time to overall response of 9 months are reported.

End point type

Secondary

End point timeframe

End point values	TG4010	Placebo	TG4010: Normal TrPAL Subgroup	Placebo: Normal TrPAL Subgroup	TG4010: High TrPAL Subgroup	Placebo: High TrPAL Subgroup	TG4010: Non-elevated TrPAL Subgroup	Placebo: Non-elevated TrPAL Subgroup	TG4010: Elevated TrPAL Subgroup	Placebo: Elevated TrPal Subgroup
Number of subjects analysed	111	111	85	85	26	26	71	76	40	35
Units: Percentage of Subjects
number (confidence interval 95%)	42 (27 to 56)	59 (47 to 70)	45 (28 to 60)	59 (46 to 70)	33 (8 to 62)	61 (32 to 81)	49 (34 to 62)	57 (43 to 69)	29 (7 to 57)	65 (41 to 81)

Comparison of TOR in Whole Population

Statistical analysis description

The distribution of TOR was compared between the treatment arms using a one-sided non-stratified log-rank test. Hazard ratio and corresponding 95% CIs were derived using the Cox proportional hazards model.

Comparison groups

Placebo v TG4010

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.108

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

2.1

Comparison of TOR in Normal TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: Normal TrPAL Subgroup v Placebo: Normal TrPAL Subgroup

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.218

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

2.05

Comparison of TOR in High TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: High TrPAL Subgroup v Placebo: High TrPAL Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.152

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

4.51

Comparison of TOR in Non-elevated TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: Non-elevated TrPAL Subgroup v Placebo: Non-elevated TrPAL Subgroup

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.315

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

1.97

Comparison of TOR in Elevated TrPAL Subgroup

Statistical analysis description

Comparison groups

TG4010: Elevated TrPAL Subgroup v Placebo: Elevated TrPal Subgroup

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.082

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

4.22

Secondary: Duration of Overall Response (DOR) in Subjects Treated with TG4010 or Placebo.

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End point title

Duration of Overall Response (DOR) in Subjects Treated with TG4010 or Placebo.

End point description

DOR in weeks applied only to patients whose best overall tumour response was CR or PR. The start date was the date of first documented response (CR or PR) and the end date was the date of event defined as first documented disease progression or death due to underlying cancer. DoR was censored if progression or death due to underlying cancer was not observed at the cut-off date for the analysis or start of further antineoplastic therapy. The censoring date was the date of the last evaluable tumour assessment. For the purpose of reporting data, where the result was recorded as 'not reached' (i.e. infinity) an arbitrary value of 999999 has been assigned.

End point type

Secondary

End point timeframe

End point values	TG4010	Placebo	TG4010: Normal TrPAL Subgroup	Placebo: Normal TrPAL Subgroup	TG4010: High TrPAL Subgroup	Placebo: High TrPAL Subgroup	TG4010: Non-elevated TrPAL Subgroup	Placebo: Non-elevated TrPAL Subgroup	TG4010: Elevated TrPAL Subgroup	Placebo: Elevated TrPal Subgroup
Number of subjects analysed	44 ^[13]	32 ^[14]	33 ^[15]	26 ^[16]	11 ^[17]	6 ^[18]	28 ^[19]	24 ^[20]	16 ^[21]	8 ^[22]
Units: weeks
median (confidence interval 95%)	30.1 (21.9 to 43.1)	18.7 (14.9 to 36.4)	31 (19.9 to 54.1)	20.4 (14.3 to 36.4)	27.4 (12.3 to 55.4)	17.2 (11.1 to 999999)	41.4 (19.9 to 54.7)	18.7 (13.4 to 30.3)	27.4 (15.6 to 40.9)	32.2 (11.1 to 999999)

Notes
[13] - Only subjects whose best overall response was classed as CR or PR were analysed.
[14] - Only subjects whose best overall response was classed as CR or PR were analysed.
[15] - Only subjects whose best overall response was classed as CR or PR were analysed.
[16] - Only subjects whose best overall response was classed as CR or PR were analysed.
[17] - Only subjects whose best overall response was classed as CR or PR were analysed.
[18] - Only subjects whose best overall response was classed as CR or PR were analysed (999999=infinity).
[19] - Only subjects whose best overall response was classed as CR or PR were analysed.
[20] - Only subjects whose best overall response was classed as CR or PR were analysed.
[21] - Only subjects whose best overall response was classed as CR or PR were analysed.
[22] - Only subjects whose best overall response was classed as CR or PR were analysed (999999=infinity).

No statistical analyses for this end point

Secondary: Number of DOR Events in Subjects Treated with TG4010 or Placebo.

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End point title

Number of DOR Events in Subjects Treated with TG4010 or Placebo.

End point description

DOR applied only to patients whose best overall tumour response was CR or PR and number of DOR events were recorded for ach treatment arm and subgroup. DOR was censored if progression or death due to underlying cancer was not observed at the cut-off date for the analysis or start of further antineoplastic therapy. The censoring date was the date of the last evaluable tumour assessment.

End point type

Secondary

End point timeframe

End point values	TG4010	Placebo	TG4010: Normal TrPAL Subgroup	Placebo: Normal TrPAL Subgroup	TG4010: High TrPAL Subgroup	Placebo: High TrPAL Subgroup	TG4010: Non-elevated TrPAL Subgroup	Placebo: Non-elevated TrPAL Subgroup	TG4010: Elevated TrPAL Subgroup	Placebo: Elevated TrPal Subgroup
Number of subjects analysed	44 ^[23]	32 ^[24]	33 ^[25]	26 ^[26]	11 ^[27]	6 ^[28]	28 ^[29]	24 ^[30]	16 ^[31]	8 ^[32]
Units: DOR Events	35	28	27	23	8	5	22	22	13	6

Notes
[23] - Only subjects whose best overall response was classed as CR or PR were analysed.
[24] - Only subjects whose best overall response was classed as CR or PR were analysed.
[25] - Only subjects whose best overall response was classed as CR or PR were analysed.
[26] - Only subjects whose best overall response was classed as CR or PR were analysed.
[27] - Only subjects whose best overall response was classed as CR or PR were analysed.
[28] - Only subjects whose best overall response was classed as CR or PR were analysed.
[29] - Only subjects whose best overall response was classed as CR or PR were analysed.
[30] - Only subjects whose best overall response was classed as CR or PR were analysed.
[31] - Only subjects whose best overall response was classed as CR or PR were analysed.
[32] - Only subjects whose best overall response was classed as CR or PR were analysed.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From the first day of study treatment until 28 days after the last dose of study treatment (up to a maximum of 107 weeks + 28 days).

Adverse event reporting additional description

Adverse events were summarised by treatment arm (TG4010 or placebo) in subjects that had received at least one injection ofTG4010 or placebo (110 patients in TG4010 arm and 107 patients in the placebo arm). Causality was assessed in relation to TG4010 or placebo.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

TG4010

Reporting group description

Subjects received TG4010 plus chemotherapy as first-line treatment followed by TG4010 plus maintenance therapy if appropriate. TG4010 was administered on Day 1 of Cycle 1 of chemotherapy and then weekly for 6 weeks by SC injections, then once every 3 weeks until disease progression or premature discontinuation. Chemotherapy was given as 21-day cycles for a minimum of 4 cycles and up to 6 cycles. If prescribed, bevacizumab was continued in combination with TG4010 and administered every 3 weeks until disease progression, premature discontinuation, or toxicity.

Reporting group title

Placebo

Reporting group description

Subjects received TG4010 plus chemotherapy as first-line treatment followed by placebo plus maintenance therapy if appropriate. Placebo was administered on Day 1 of Cycle 1 of chemotherapy and then weekly for 6 weeks by SC injections, then once every 3 weeks until disease progression or premature discontinuation. Chemotherapy was given as 21-day cycles for a minimum of 4 cycles and up to 6 cycles. If prescribed, bevacizumab was continued in combination with placebo and administered every 3 weeks until disease progression, premature discontinuation, or toxicity.

Serious adverse events	TG4010	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	51 / 110 (46.36%)	58 / 107 (54.21%)
number of deaths (all causes)	18	14
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	1 / 110 (0.91%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endometrial cancer
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to bone
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to meninges
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Metastatic pain
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tumour associated fever
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Peripheral ischaemia
subjects affected / exposed	2 / 110 (1.82%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Superior vena cava syndrome
subjects affected / exposed	0 / 110 (0.00%)	3 / 107 (2.80%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 110 (0.00%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Arterial occlusive disease
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Iliac artery occlusion
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombophlebitis superficial
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
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	10 / 110 (9.09%)	8 / 107 (7.48%)
occurrences causally related to treatment / all	0 / 10	0 / 8
deaths causally related to treatment / all	0 / 8	0 / 5
Pyrexia
subjects affected / exposed	1 / 110 (0.91%)	3 / 107 (2.80%)
occurrences causally related to treatment / all	0 / 1	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Fatigue
subjects affected / exposed	2 / 110 (1.82%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden death
subjects affected / exposed	1 / 110 (0.91%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 2
Malaise
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Anaphylactic shock
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
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
Pulmonary embolism
subjects affected / exposed	4 / 110 (3.64%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	3 / 110 (2.73%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 110 (0.91%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	2 / 110 (1.82%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 1
Acute pulmonary oedema
subjects affected / exposed	1 / 110 (0.91%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 110 (0.91%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	2 / 110 (1.82%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
Acquired tracheo-oesophageal fistula
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumothorax
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 110 (0.00%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac tamponade
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery insufficiency
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pericardial effusion
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebral ischaemia
subjects affected / exposed	1 / 110 (0.91%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Brain oedema
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Convulsion
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Generalised non-convulsive epilepsy
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 110 (1.82%)	3 / 107 (2.80%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 110 (0.91%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Febrile bone marrow aplasia
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	3 / 110 (2.73%)	6 / 107 (5.61%)
occurrences causally related to treatment / all	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Diplopia
subjects affected / exposed	1 / 110 (0.91%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	1 / 110 (0.91%)	5 / 107 (4.67%)
occurrences causally related to treatment / all	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	2 / 110 (1.82%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 110 (0.00%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 110 (0.00%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer perforation
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Renal failure
subjects affected / exposed	0 / 110 (0.00%)	3 / 107 (2.80%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 110 (0.00%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bone pain
subjects affected / exposed	0 / 110 (0.00%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	2 / 110 (1.82%)	4 / 107 (3.74%)
occurrences causally related to treatment / all	0 / 2	2 / 6
deaths causally related to treatment / all	0 / 1	0 / 0
Respiratory tract infection
subjects affected / exposed	3 / 110 (2.73%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Erysipelas
subjects affected / exposed	2 / 110 (1.82%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 110 (0.91%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lobar pneumonia
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Localised infection
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infection
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pyelonephritis
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	3 / 110 (2.73%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 110 (0.00%)	2 / 107 (1.87%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Food intolerance
subjects affected / exposed	0 / 110 (0.00%)	1 / 107 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 110 (0.91%)	0 / 107 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	TG4010	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	109 / 110 (99.09%)	102 / 107 (95.33%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	10 / 110 (9.09%)	6 / 107 (5.61%)
occurrences all number	10	6
Vascular disorders
Hypertension
subjects affected / exposed	9 / 110 (8.18%)	13 / 107 (12.15%)
occurrences all number	10	16
Hypotension
subjects affected / exposed	9 / 110 (8.18%)	3 / 107 (2.80%)
occurrences all number	9	4
General disorders and administration site conditions
Fatigue
subjects affected / exposed	60 / 110 (54.55%)	59 / 107 (55.14%)
occurrences all number	91	81
Injection site erythema
subjects affected / exposed	17 / 110 (15.45%)	1 / 107 (0.93%)
occurrences all number	28	1
Injection site induration
subjects affected / exposed	9 / 110 (8.18%)	0 / 107 (0.00%)
occurrences all number	12	0
Injection site pain
subjects affected / exposed	13 / 110 (11.82%)	1 / 107 (0.93%)
occurrences all number	23	1
Oedema peripheral
subjects affected / exposed	22 / 110 (20.00%)	19 / 107 (17.76%)
occurrences all number	26	21
Pyrexia
subjects affected / exposed	15 / 110 (13.64%)	11 / 107 (10.28%)
occurrences all number	20	12
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	19 / 110 (17.27%)	22 / 107 (20.56%)
occurrences all number	20	25
Dyspnoea
subjects affected / exposed	28 / 110 (25.45%)	14 / 107 (13.08%)
occurrences all number	29	15
Epistaxis
subjects affected / exposed	12 / 110 (10.91%)	11 / 107 (10.28%)
occurrences all number	13	14
Haemoptysis
subjects affected / exposed	2 / 110 (1.82%)	8 / 107 (7.48%)
occurrences all number	2	9
Productive Cough
subjects affected / exposed	8 / 110 (7.27%)	6 / 107 (5.61%)
occurrences all number	9	7
Rhinorrhoea
subjects affected / exposed	8 / 110 (7.27%)	1 / 107 (0.93%)
occurrences all number	9	1
Psychiatric disorders
Anxiety
subjects affected / exposed	12 / 110 (10.91%)	4 / 107 (3.74%)
occurrences all number	12	4
Insomnia
subjects affected / exposed	8 / 110 (7.27%)	5 / 107 (4.67%)
occurrences all number	8	5
Investigations
Blood creatinine increased
subjects affected / exposed	9 / 110 (8.18%)	5 / 107 (4.67%)
occurrences all number	10	6
Weight decreased
subjects affected / exposed	21 / 110 (19.09%)	19 / 107 (17.76%)
occurrences all number	22	21
Weight increased
subjects affected / exposed	5 / 110 (4.55%)	7 / 107 (6.54%)
occurrences all number	5	7
Nervous system disorders
Dizziness
subjects affected / exposed	9 / 110 (8.18%)	3 / 107 (2.80%)
occurrences all number	11	5
Dysgeusia
subjects affected / exposed	13 / 110 (11.82%)	9 / 107 (8.41%)
occurrences all number	15	9
Headache
subjects affected / exposed	14 / 110 (12.73%)	11 / 107 (10.28%)
occurrences all number	15	12
Neuropathy Peripheral
subjects affected / exposed	4 / 110 (3.64%)	8 / 107 (7.48%)
occurrences all number	6	10
Paraesthesia
subjects affected / exposed	11 / 110 (10.00%)	13 / 107 (12.15%)
occurrences all number	11	18
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	50 / 110 (45.45%)	38 / 107 (35.51%)
occurrences all number	66	50
Leukopenia
subjects affected / exposed	10 / 110 (9.09%)	11 / 107 (10.28%)
occurrences all number	11	16
Lymphopenia
subjects affected / exposed	4 / 110 (3.64%)	7 / 107 (6.54%)
occurrences all number	5	9
Neutropenia
subjects affected / exposed	49 / 110 (44.55%)	38 / 107 (35.51%)
occurrences all number	119	85
Thrombocytopenia
subjects affected / exposed	27 / 110 (24.55%)	20 / 107 (18.69%)
occurrences all number	42	32
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	11 / 110 (10.00%)	7 / 107 (6.54%)
occurrences all number	11	9
Eye disorders
Lacrimation Increased
subjects affected / exposed	7 / 110 (6.36%)	5 / 107 (4.67%)
occurrences all number	8	5
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	15 / 110 (13.64%)	9 / 107 (8.41%)
occurrences all number	16	13
Abdominal Pain upper
subjects affected / exposed	10 / 110 (9.09%)	8 / 107 (7.48%)
occurrences all number	10	9
Constipation
subjects affected / exposed	22 / 110 (20.00%)	29 / 107 (27.10%)
occurrences all number	26	35
Diarrhoea
subjects affected / exposed	27 / 110 (24.55%)	21 / 107 (19.63%)
occurrences all number	35	31
Nausea
subjects affected / exposed	54 / 110 (49.09%)	44 / 107 (41.12%)
occurrences all number	89	76
Stomatitis
subjects affected / exposed	9 / 110 (8.18%)	14 / 107 (13.08%)
occurrences all number	12	15
Vomiting
subjects affected / exposed	32 / 110 (29.09%)	35 / 107 (32.71%)
occurrences all number	47	68
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	13 / 110 (11.82%)	8 / 107 (7.48%)
occurrences all number	13	8
Erythema
subjects affected / exposed	6 / 110 (5.45%)	6 / 107 (5.61%)
occurrences all number	8	6
Rash
subjects affected / exposed	6 / 110 (5.45%)	5 / 107 (4.67%)
occurrences all number	9	6
Renal and urinary disorders
Renal Failure
subjects affected / exposed	3 / 110 (2.73%)	8 / 107 (7.48%)
occurrences all number	4	8
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	9 / 110 (8.18%)	8 / 107 (7.48%)
occurrences all number	11	12
Back pain
subjects affected / exposed	14 / 110 (12.73%)	12 / 107 (11.21%)
occurrences all number	15	13
Musculoskeletal pain
subjects affected / exposed	10 / 110 (9.09%)	4 / 107 (3.74%)
occurrences all number	10	5
Myalgia
subjects affected / exposed	7 / 110 (6.36%)	3 / 107 (2.80%)
occurrences all number	7	4
Pain in Extremity
subjects affected / exposed	16 / 110 (14.55%)	6 / 107 (5.61%)
occurrences all number	18	10
Infections and infestations
Bronchitis
subjects affected / exposed	10 / 110 (9.09%)	11 / 107 (10.28%)
occurrences all number	11	12
Respiratory tract infection
subjects affected / exposed	6 / 110 (5.45%)	4 / 107 (3.74%)
occurrences all number	7	5
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	24 / 110 (21.82%)	27 / 107 (25.23%)
occurrences all number	30	32
Hypokalaemia
subjects affected / exposed	7 / 110 (6.36%)	13 / 107 (12.15%)
occurrences all number	8	16
Hyponatraemia
subjects affected / exposed	7 / 110 (6.36%)	6 / 107 (5.61%)
occurrences all number	7	6

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Were there any global substantial amendments to the protocol? Yes

26 Apr 2012

Major changes included the following: • Inclusion criteria were modified for some laboratory parameters and additional laboratory parameters were added for routine monitoring (e.g. bilirubin) • TOR was added as a secondary objective • PS was added as a stratification factor for statistical analyses (as it is a stratification factor in the randomisation process) • Changes were made to the sensitivity analyses and secondary objectives for the Phase III part of the study

02 Jul 2013

Major changes included the following: • An exploratory objective evaluating the response rate (i.e. proportion of patients with CR or PR) at tumour evaluation #2 was added • The statistical methods were modified to allow for a preliminary analysis of the subgroup of patients with a high level of TrPAL, at the same time as the primary analysis was performed in the subgroup of patients with normal TrPAL

06 Nov 2013

Major changes included the following: • Due to the increased time lag in the occurrence of the required number of PFS events in the subgroups of normal and high TrPAL patients necessary for the final analysis, implicating that final analysis in each subgroup could not be performed at the same time, time points for unblinding were revised and delayed for the high TrPAL subgroup until the final analysis results were available in this subgroup to avoid the introduction of possible biases.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
06 Jul 2015	A decision was taken by the sponsor for business reasons to not proceed with Phase III part after the completion of Phase IIb.	-

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

Due to the early termination of this study, this results posting is a complete record of the Phase IIb part of the study only. Phase III did not proceed and is therefore not included in any part.

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Clinical trials

Clinical Trial Results:
A Phase IIb/III randomised, double-blind, placebo-controlled study comparing first-line therapy with or without TG4010 immunotherapy product in patients with stage IV non-small cell lung cancer (NSCLC).

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Comparison of PFS Events in Subjects Treated with TG4010 or Placebo.

Primary: Comparison of PFS Events in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of OS Events in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of OS Events in Subjects Treated with TG4010 or Placebo.

Secondary: Median OS in Subjects Treated with TG4010 or Placebo.

Secondary: Median OS in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of Overall Response Rate (ORR) in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of Overall Response Rate (ORR) in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of Percentage of Subjects with a 9 Month Time to Overall Response (TOR) in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of Percentage of Subjects with a 9 Month Time to Overall Response (TOR) in Subjects Treated with TG4010 or Placebo.

Secondary: Duration of Overall Response (DOR) in Subjects Treated with TG4010 or Placebo.

Secondary: Duration of Overall Response (DOR) in Subjects Treated with TG4010 or Placebo.

Secondary: Number of DOR Events in Subjects Treated with TG4010 or Placebo.

Secondary: Number of DOR Events in Subjects Treated with TG4010 or Placebo.

Adverse events

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Substantial protocol amendments (globally)

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Belgium
Bulgaria
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Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
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Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
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Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase IIb/III randomised, double-blind, placebo-controlled study comparing first-line therapy with or without TG4010 immunotherapy product in patients with stage IV non-small cell lung cancer (NSCLC).

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Comparison of PFS Events in Subjects Treated with TG4010 or Placebo.

Primary: Comparison of PFS Events in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of OS Events in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of OS Events in Subjects Treated with TG4010 or Placebo.

Secondary: Median OS in Subjects Treated with TG4010 or Placebo.

Secondary: Median OS in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of Overall Response Rate (ORR) in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of Overall Response Rate (ORR) in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of Percentage of Subjects with a 9 Month Time to Overall Response (TOR) in Subjects Treated with TG4010 or Placebo.

Secondary: Comparison of Percentage of Subjects with a 9 Month Time to Overall Response (TOR) in Subjects Treated with TG4010 or Placebo.

Secondary: Duration of Overall Response (DOR) in Subjects Treated with TG4010 or Placebo.

Secondary: Duration of Overall Response (DOR) in Subjects Treated with TG4010 or Placebo.

Secondary: Number of DOR Events in Subjects Treated with TG4010 or Placebo.

Secondary: Number of DOR Events in Subjects Treated with TG4010 or Placebo.

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase IIb/III randomised, double-blind, placebo-controlled study comparing first-line therapy with or without TG4010 immunotherapy product in patients with stage IV non-small cell lung cancer (NSCLC).