Clinical Trial Results:
A double-blind, randomized, placebo-controlled Phase III study to assess the efficacy of recMAGE-A3 + AS15 Antigen-Specific Cancer Immunotherapeutic as adjuvant therapy in patients with resectable MAGE-A3-positive Non-Small Cell Lung Cancer
Summary
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EudraCT number |
2007-001283-73 |
Trial protocol |
BE DE IE FI ES SI FR SE GR IT LV AT NL HU CZ EE GB |
Global end of trial date |
23 Sep 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
13 Dec 2020
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First version publication date |
03 Mar 2016
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
109493
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00480025 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline Biologicals
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Sponsor organisation address |
Rue de l’Institut 89, Rixensart, Belgium, B-1330
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Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Dec 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Sep 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this Phase III study is to demonstrate the clinical efficacy (in terms of disease-free survival) of recMAGE-A3 + AS15 versus placebo in NSCLC after complete surgical resection.
three co-primary objectives are considered:
•Objective A: Efficacy in the overall population;
•Objective B: Efficacy in the population of patients who did not receive adjuvant chemotherapy (no-CT population).
•Objective C: Efficacy in the population of patients presenting the potentially favourable gene signature.
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Protection of trial subjects |
Patients were observed closely for at least 30 minutes following treatment, with appropriate medical treatment readily available in case of a rare anaphylactic reaction. MAGE-A3 ASCI/placebo were administered by qualified and trained personnel, only to eligible subjects with no contraindications to any components of these products. During treatment, the following was checked to assess need to postpone treatment: acute disease at time of administration; any systemic grade ≥ 2 Common Terminology Criteria Adverse Event related or possibly related to treatment; fever, defined as an oral, axillary or tympanic temperature =< 38°C; need for influenza vaccine, immunoglobulins and/or any blood products; any medical reason exposing the patient to unacceptable risk. Patients were required to discontinue treatment in case of evidence of disease relapse/occurrence of second primary lung cancer; treatment with either investigational or non-registered product other than MAGE-A3 ASCI study product or other anticancer treatments; anaphylactic reaction following treatment administration; any intolerable adverse event; clinical signs or symptoms indicative of any autoimmune disorder, except vitiligo; appearance of any confirmed or suspected immunosuppressive or immunodeficient condition, or any condition requiring use of any immunosuppressive agent or systemic corticosteroids prescribed for chronic use; inability of the patient to complete study evaluations due to unforeseen circumstances; other conditions indicating the patient’s best interest to be withdrawn from treatment. In addition, between the end of the 120-weeks treatment phase, the following follow-up (FU) of patients was also planned: 1) an active FU for survival, recurrence, serious adverse events related to treatment & SAEs related to study participation and concurrent GSK medication of up to 5 years from the 1st treatment, and 2) annual contacts up to 10 years after 1st treatment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Oct 2007
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
8 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 10
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Country: Number of subjects enrolled |
Australia: 25
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Country: Number of subjects enrolled |
Brazil: 21
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Country: Number of subjects enrolled |
Canada: 37
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Country: Number of subjects enrolled |
Netherlands: 24
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Country: Number of subjects enrolled |
Norway: 22
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Country: Number of subjects enrolled |
Poland: 166
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Country: Number of subjects enrolled |
Spain: 86
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Country: Number of subjects enrolled |
Sweden: 12
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Country: Number of subjects enrolled |
United Kingdom: 83
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Country: Number of subjects enrolled |
Austria: 26
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Country: Number of subjects enrolled |
Belgium: 35
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Country: Number of subjects enrolled |
Czech Republic: 50
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Country: Number of subjects enrolled |
Estonia: 57
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Country: Number of subjects enrolled |
Finland: 9
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Country: Number of subjects enrolled |
France: 107
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Country: Number of subjects enrolled |
Germany: 268
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Country: Number of subjects enrolled |
Greece: 97
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Country: Number of subjects enrolled |
Hungary: 57
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Country: Number of subjects enrolled |
Ireland: 8
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Country: Number of subjects enrolled |
Italy: 113
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Country: Number of subjects enrolled |
China: 159
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Country: Number of subjects enrolled |
Hong Kong: 10
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Country: Number of subjects enrolled |
India: 13
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Country: Number of subjects enrolled |
Israel: 16
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Country: Number of subjects enrolled |
Japan: 210
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Country: Number of subjects enrolled |
Korea, Republic of: 108
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Country: Number of subjects enrolled |
Russian Federation: 55
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Country: Number of subjects enrolled |
Singapore: 1
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Country: Number of subjects enrolled |
Switzerland: 11
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Country: Number of subjects enrolled |
Taiwan: 31
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Country: Number of subjects enrolled |
Thailand: 20
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Country: Number of subjects enrolled |
Ukraine: 22
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Country: Number of subjects enrolled |
United States: 343
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Worldwide total number of subjects |
2312
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EEA total number of subjects |
1220
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1251
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From 65 to 84 years |
1055
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85 years and over |
6
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Recruitment
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Recruitment details |
A total of 2315 patients were screened towards participation in the study. For 3 of these subjects informed consent forms issues were reported, and thus only 2312 subjects were considered for analyses/results Out of these 2312 subjects, 2278 were enrolled in the study. | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Out of the 2278 enrolled patients, only 2272 patients received at least one dose of study treatment (1515 received MAGE-A3 ASCI and 757 received placebo). | ||||||||||||||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
2312 | ||||||||||||||||||||||||||||||
Number of subjects completed |
2272 | ||||||||||||||||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Not treated: 40 | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Entire Study Period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||||||||||||||
Blinding implementation details |
Because the final establishment of the gene expression signature classifier by testing the samples on the training set was to only start after a positive interim analysis or after the final analysis of DFS in the overall/no-CT population, Disease Free Survival (DFS) in the GS+ population was to be analyzed at a later time point. Therefore, the Sponsor, investigators and patients should remain blinded to the treatment assignment until analysis of DFS in the GS+ population.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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MAGE-A3 Total Group | ||||||||||||||||||||||||||||||
Arm description |
Patients received up to 13 doses (D) of MAGE-A3 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
recMAGE-A3 recombinant protein formulated in AS15 adjuvant
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Investigational medicinal product code |
recMAGE-A3 + AS15
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Other name |
MAGE-A3 ASCI, MAGE-A3 ASCI product, GSK1572932A
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Pharmaceutical forms |
Powder and suspension for suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Up to 13 doses via intramuscular injections in the deltoid or lateral region of the thigh preferably alternating on right and left side.
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Arm title
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Placebo Total Group | ||||||||||||||||||||||||||||||
Arm description |
Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
Sucrose reconstituted with an oil-in-water emulsion
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Pharmaceutical forms |
Powder and suspension for suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Up to 13 doses via intramuscular injections in the deltoid or lateral region of the thigh preferably alternating on right and left side.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Out of the 2312 enrolled patients, not all started treatment, only 2272 patients started the trial. |
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Baseline characteristics reporting groups
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Reporting group title |
MAGE-A3 Total Group
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Reporting group description |
Patients received up to 13 doses (D) of MAGE-A3 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Total Group
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Reporting group description |
Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
MAGE-A3 CT Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients received up to 13 doses (D) of MAGE-A3 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had received adjuvant chemotherapy prior to randomization (CT Population).
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Subject analysis set title |
Placebo CT Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had received adjuvant chemotherapy prior to randomization (CT Population).
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Subject analysis set title |
MAGE-A3 No-CT Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients received up to 13 doses (D) of MAGE-A3 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had not received adjuvant chemotherapy prior to randomization (No-CT Population).
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Subject analysis set title |
Placebo No-CT Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had not received adjuvant chemotherapy prior to randomization (No-CT Population).
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End points reporting groups
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Reporting group title |
MAGE-A3 Total Group
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Reporting group description |
Patients received up to 13 doses (D) of MAGE-A3 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. | ||
Reporting group title |
Placebo Total Group
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Reporting group description |
Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. | ||
Subject analysis set title |
MAGE-A3 CT Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients received up to 13 doses (D) of MAGE-A3 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had received adjuvant chemotherapy prior to randomization (CT Population).
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Subject analysis set title |
Placebo CT Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had received adjuvant chemotherapy prior to randomization (CT Population).
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Subject analysis set title |
MAGE-A3 No-CT Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients received up to 13 doses (D) of MAGE-A3 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had not received adjuvant chemotherapy prior to randomization (No-CT Population).
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Subject analysis set title |
Placebo No-CT Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had not received adjuvant chemotherapy prior to randomization (No-CT Population).
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End point title |
Person year rate (PYAR) as regards disease-free survival (DFS) in the overall population | |||||||||||||||
End point description |
DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional & distant metastasis & 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; & distant recurrence [any tumor arising in contralateral lung or outside hemithorax]). Deaths occurring without prior documentation of recurrence were considered as event & not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.
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End point type |
Primary
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End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
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Statistical analysis title |
DFS Comparing MAGE-A3 vs placebo – All Patients | |||||||||||||||
Statistical analysis description |
Analysis compared DFS PYAR between groups for period from 1st treatment dose to DLP. A Cox model was used to evaluate treatment efficacy (TE). TE was calculated as PYAR in MAGE-A3 Total Group (PYAR1) divided by PYAR in Placebo Total Group (PYAR2), and weighed for adjustment factors. This comparison in all patients (overall population) also included taking into account stratification by previous CT vs. No-CT treatment and weighing using randomization-minimization factors (RMF) as regressors.
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Comparison groups |
MAGE-A3 Total Group v Placebo Total Group
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Number of subjects included in analysis |
2272
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | |||||||||||||||
P-value |
= 0.7379 [2] | |||||||||||||||
Method |
Regression, Cox | |||||||||||||||
Parameter type |
TE | |||||||||||||||
Point estimate |
1.024
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
0.891 | |||||||||||||||
upper limit |
1.177 | |||||||||||||||
Notes [1] - RMF taken into account included: 1) Number of chemotherapy cycles received (1, 2 vs. 3, 4), if any; 2) Pathological stage of the disease (IB vs. II vs. IIIA); 3) Type of lymph-node sampling (minimal lymph-node sampling vs. systematic radical mediastinal lymphadenectomy); 4) ECOG performance status randomization (0, 1 vs. 2); 5) Smoking status ( 100 cigarettes a lifetime vs. > 100 cigarettes and current smoker vs. > 100 cigarettes and past smoker). [2] - 2-sided p-value of Likelihood Ratio test from RMF-adjusted Cox regression, Efron method used to handle ties. Overall population objective reached if p-value < 2%/4% in absence/presence of statistically significant effect in the No-CT population. |
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End point title |
Person year rate (PYAR) as regards disease-free survival (DFS) in the No-CT population | |||||||||||||||
End point description |
DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional & distant metastasis & 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; & distant recurrence [any tumor arising in contralateral lung or outside hemithorax]). Deaths occurring without prior documentation of recurrence were considered as event & not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.
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End point type |
Primary
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End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
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Statistical analysis title |
DFS Comparing MAGE-A3 vs placebo – No-CT Patients | |||||||||||||||
Statistical analysis description |
Analysis compared DFS PYAR between groups for the period from 1st treatment dose to DLP. A Cox model was used to evaluate treatment efficacy (TE). TE was calculated as PYAR in MAGE-A3 No-CT Group (PYAR1) divided by PYAR in Placebo No-CT Group (PYAR2) and weighed for adjustment factors. This comparison in all patients (overall population) also included taking into account weighing using randomization-minimization factors (RMF) as regressors.
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Comparison groups |
MAGE-A3 No-CT Group v Placebo No-CT Group
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Number of subjects included in analysis |
1096
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | |||||||||||||||
P-value |
= 0.7572 [4] | |||||||||||||||
Method |
Regression, Cox | |||||||||||||||
Parameter type |
TE | |||||||||||||||
Point estimate |
0.97
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
0.797 | |||||||||||||||
upper limit |
1.179 | |||||||||||||||
Notes [3] - RMF included: 1) Number of chemotherapy cycles received (1, 2 vs. 3, 4), if any; 2) Pathological stage of the disease (IB vs. II vs. IIIA); 3) Type of lymph-node sampling (minimal lymph-node sampling vs. systematic radical mediastinal lymphadenectomy); 4) ECOG performance status randomization (0, 1 vs. 2); 5) Smoking status ( 100 cigarettes a lifetime vs. > 100 cigarettes and current smoker vs. > 100 cigarettes and past smoker). [4] - 2-sided p-value of Likelihood Ratio test from RMF-adjusted Cox regression, Efron method used to handle ties. No-CT population objective reached if p-value < 2.56%/4% in absence/presence of statistically significant effect in the No-CT population. |
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End point title |
Person year rate (PYAR) as regards disease-free survival (DFS) in the CT population | |||||||||||||||
End point description |
DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional & distant metastasis & 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; & distant recurrence [any tumor arising in contralateral lung or outside hemithorax]). Deaths occurring without prior documentation of recurrence were considered as event & not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards overall-survival (OS) in the overall population | |||||||||||||||
End point description |
OS was defined as the time interval from randomization to the date of death, irrespective of the cause of death. Patients still alive were censored at the last visit they were known to be alive. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median OS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards overall-survival (OS) in the No-CT population | |||||||||||||||
End point description |
OS was defined as the time interval from randomization to the date of death, irrespective of the cause of death. Patients still alive were censored at the last visit they were known to be alive. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median OS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards overall-survival (OS) in the CT population | |||||||||||||||
End point description |
OS was defined as the time interval from randomization to the date of death, irrespective of the cause of death. Patients still alive were censored at the last visit they were known to be alive. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median OS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards lung-cancer specific survival (LCSS) in the Overall population | |||||||||||||||
End point description |
LCSS was defined as the time interval from randomization to the date of death due to lung cancer. Deaths due to other or unknown causes were censored at the date of death. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median OS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards lung-cancer specific survival (LCSS) in the No-CT population | |||||||||||||||
End point description |
LCSS was defined as the time interval from randomization to the date of death due to lung cancer. Deaths due to other or unknown causes were censored at the date of death. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median OS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards lung-cancer specific survival (LCSS) in the CT population | |||||||||||||||
End point description |
LCSS was defined as the time interval from randomization to the date of death due to lung cancer. Deaths due to other or unknown causes were censored at the date of death. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median OS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Kaplan-Meier estimate (KME) of 2, 3, 4 and 5-year as regards disease-free survival (DFS) in the overall population | ||||||||||||||||||||||||
End point description |
DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional & distant metastasis & 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; & distant recurrence [any tumor arising in contralateral lung or outside hemithorax]). Deaths occurring without prior documentation of recurrence were considered as event & not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. Median DFS KMEs in % were obtained non-parametrically by Kaplan-Meier method and confidence intervals (CIs) calculated using the Greenwood formula for standard error computation.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
KME assessed at 2, 3, 4 and 5-year (Y) post Dose 1 of treatment. Follow-up period was from administration of 1st dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Kaplan-Meier estimate (KME) of 2, 3, 4 and 5-year as regards disease-free survival (DFS) in the No-CT population | ||||||||||||||||||||||||
End point description |
DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional & distant metastasis & 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; & distant recurrence [any tumor arising in contralateral lung or outside hemithorax]). Deaths occurring without prior documentation of recurrence were considered as event & not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. Median DFS KMEs in % were obtained non-parametrically by Kaplan-Meier method and confidence intervals (CIs) calculated using the Greenwood formula for standard error computation.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
KME assessed at 2, 3, 4 and 5-year (Y) post Dose 1 of treatment Follow-up period was from administration of 1st dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Kaplan-Meier estimate (KME) of 2, 3, 4 and 5-year as regards disease-free survival (DFS) in the CT population | ||||||||||||||||||||||||
End point description |
DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional & distant metastasis & 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; & distant recurrence [any tumor arising in contralateral lung or outside hemithorax]). Deaths occurring without prior documentation of recurrence were considered as event & not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. Median DFS KMEs in % were obtained non-parametrically by Kaplan-Meier method and confidence intervals (CIs) calculated using the Greenwood formula for standard error computation.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
KME assessed at 2, 3, 4 and 5-year (Y) post Dose 1 of treatment. Follow-up period was from administration of 1st dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards disease-free specific survival (DFSS) in the overall population | |||||||||||||||
End point description |
DFSS was defined as the interval from randomization to the date of disease recurrence or death due to lung cancer. Patients who had died due to another cause than lung cancer were censored on their date of death and patients alive at the time of analysis were censored on the date of last assessment. Patients with no assessment post-randomization were censored on the date of randomization. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards disease-free specific survival (DFSS) in the No-CT population | |||||||||||||||
End point description |
DFSS was defined as the interval from randomization to the date of disease recurrence or death due to lung cancer. Patients who had died due to another cause than lung cancer were censored on their date of death and patients alive at the time of analysis were censored on the date of last assessment. Patients with no assessment post-randomization were censored on the date of randomization. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Person year rate (PYAR) as regards disease-free specific survival (DFSS) in the CT population | |||||||||||||||
End point description |
DFSS was defined as the interval from randomization to the date of disease recurrence or death due to lung cancer. Patients who had died due to another cause than lung cancer were censored on their date of death and patients alive at the time of analysis were censored on the date of last assessment. Patients with no assessment post-randomization were censored on the date of randomization. PYAR = n (=number of subjects reported with at least 1 event) divided by T (=sum of follow-up period [in years] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Period of follow-up was from administration of first dose of MAGE-A3 ASCI study product/placebo solution to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of subjects seropositive for anti-Melanoma AntiGEn (MAGE)-A3 antibodies (Anti-MAGE-A3 S+) | |||||||||||||||||||||||||||||||||
End point description |
A seropositive subject for anti-MAGE-A3 antibodies was a subject with anti-MAGE-A3 antibodies >= the seropositivity cut-off of 27 Enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL).
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Pre-treatment (PRE), at Weeks (W) 6 and 12, at Months (M) 9, 12, 18 and 30 and at one year after treatment concluding time point, i.e. at follow-up visit 2 at W120 added of one year (At 12M post W120)
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Number of humoral responders as regards anti-Melanoma AntiGEn (MAGE)-A3 antibodies (Anti-MAGE-A3 HR) | ||||||||||||||||||||||||||||||
End point description |
A seropositive/seronegative subject for anti-MAGE-A3 antibodies was a subject with anti-MAGE-A3 antibodies >=/< the seropositivity cut-off of 27 Enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL). A humoral responder as regards anti-MAGE-A3 antibodies was defined as 1) for initially seronegative patients, a patient with post-administration Anti-MAGE-A3 antibody concentration >= 27 EL.U/mL; 2) for initially seropositive patients: post-treatment administration antibody concentration >= 2 fold the pre-treatment antibody concentration.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
At Weeks (W) 6 and 12, at Months (M) 9, 12, 18 and 30 and at one year after treatment concluding time point, i.e. at follow-up visit 2 at W120 added of one year (at 12M post W120)
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of subjects seropositive for anti-protein D (PD) antibodies (Anti-PD S+) | |||||||||||||||||||||||||||||||||
End point description |
A seropositive subject for anti-PD antibodies was a subject with anti-PD antibodies >= the seropositivity cut-off of 100 Enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL).
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Pre-treatment (PRE), at Weeks (W) 6 and 12, at Months (M) 9, 12, 18 and 30 and at one year after treatment concluding time point, i.e. at follow-up visit 2 at W120 added of one year (at 12M post W120)
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Number of humoral responders as regards anti-protein D (PD) antibodies (Anti-PD HR) | ||||||||||||||||||||||||||||||
End point description |
A seropositive/seronegative subject for anti-PD antibodies was a subject with anti-PD antibodies ≥/< the seropositivity cut-off of 100 Enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL). A humoral responder as regards anti-PD antibodies was defined as 1) for initially seronegative patients, a patient with post-administration anti-PD antibody concentration ≥ 100 EL.U/mL; 2) for initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
At Weeks (W) 6 and 12, at Months (M) 9, 12, 18 and 30 and at one year after treatment concluding time point, i.e. at follow-up visit 2 at W120 added of one year (at 12M post W120)
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Health-related quality of life (HQL) scores | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
HQL was assessed using the EQ-5D generic health state classification and valuation system. The number and percentage of patients with each score within each dimension of the EQ-5D questionnaire (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were tabulated at each assessment for each group. Each of these scores can take 3 levels: no problem (level 1), moderate problem (level 2) or extreme problem (level 3). Resulting descriptive mean and standard deviation (SD) for the EQ-5D Utility Value (EQ-5D UV) were tabulated.Valid EQ-5D data were defined as questionnaires assessed 1) on day of and before treatment administration; or 2) on day after treatment administration for W0, W6, W12; or 3)during follow-up visits or at time of recurrence. The EQ-5D total score ranges from -0.016 (worst health state) to 1.000 (best health state).
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
At Week (W) 0 on day of treatment (DoT) (W0 DoT), W0 on day post treatment (DpT) (W0 DpT), W6 DoT, W6 DpT, W12 DoT, W12 DpT, Month (M) 6, M9, M12, M24, 6M post W120, at recurrence, and at 12M post W120
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal alanine aminotransferase (ALT) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards ALT laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1 and G2. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal alanine aspartate aminotransferase (AST) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards AST laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1 and G2. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal alkaline phosphatase (ALKP) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards ALKP laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1 and G2. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal bilirubin (BIL) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards BIL laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal creatinine (CREA) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards CREA laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1 and G2. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal haemoglobin (HGB) values by maximum grade | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards HGB laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1, G2 and G3. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal leukocytes (LEU) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards LEU laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1, G2 and G3. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal lymphocytes (LYM) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards LYM laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1, G2 and G3. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal neutrophils (NEU) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards NEU laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1, G2, G3 and G4. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal platelets (PLA) values by maximum grade | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards PLA laboratory values at baseline (SCR) up to DLP was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were unknown (UNK), Grade 0 (G0), G1 and G3. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Period of follow-up was from screening (SCR) to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Number of patients with any adverse events (AEs) and with AEs by maximum grade reported – Up to data lock point (DLP) | |||||||||||||||||||||||||||
End point description |
An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs reported are here below tabulated irrespective of grade, as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1), G2, G3, G4 and G5. Any here below is defined as irrespective of CTC grade reported.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Within the 31-day follow-up period post treatment administration, up to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of patients with serious adverse events (SAEs) – Up to data lock point (DLP) | ||||||||||||
End point description |
A SAE is any untoward medical occurrence that resulted in death, was life-threatening,
required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study subject, or was a Grade 4 AE according to CTC for Adverse Events, Version 3.0. Events part of natural course of lung cancer (i.e., disease progression, recurrence) were captured towards clinical efficacy assessment (CEA) and were not reported as SAEs. Death due to a progressive disease was similarly recorded towards CEA, but not as an SAE. However, if progression of lung cancer disease was greater than normally be expected, or if investigators considered that there was a causal relationship between treatment or protocol design/procedures and disease progression/ recurrence, then it was reported as SAE. Any new cancer (non-related to lung cancer) was reported as SAE.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From screening (SCR) up to data lock point (DLP) on 23 January 2014 (up to 5 years per patient)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From screening (Day 0) up to data lock point (DLP) on 23 January 2014, for up to 5 years per patient.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
|
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Reporting group title |
MAGE-A3 Total Group
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Reporting group description |
Patients received up to 13 doses (D) of MAGE-A3 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Total Group
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Reporting group description |
Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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23 Nov 2010 |
Amendment 1 included the following changes: 1) Evaluation of efficacy of study treatment in GS+ vs GS- population was upgraded to secondary objective of the trial; 2) Analysis of impact of study treatment on patients’ health-related Quality of Life or utility was added as new secondary objective along with corresponding endpoints; 3) New, optional translational research was added including pharmacogenetic testing, DNA demethylation analysis & antigen spreading; 4) Recording of autoimmune diseases as AEs of specific interest was included in protocol & a list of types of diseases/disorders with potential autoimmune causality to be considered established; 5) Hematology & biochemistry safety laboratory tests were added for Week 12 visit; 6) Allowed concomitant medication was changed: a) systemic corticosteroids was prohibited only when prescribed for chronic treatment (more than 7 consecutive days [D]), b) immunoglobulins &/or any blood products administration was allowed provided a minimum of 7D between immunoglobulins &/or blood products & study treatment administration; 7) Study treatment postponement was allowed to permit influenza vaccination in framework of imposed influenza vaccination programs to allow a minimum of 7D between influenza vaccine & study treatment administration; 8) Clarifications were added to protocol (e.g. allowed time intervals for scans, randomization & surgery, clarifications on acceptance of scans, etc.) without changing study procedures; 9) Country specific appendices were included for countries also participating in PRAME-AS15-NSC-001 (ADJ) (GSK ID: 113174) study to allow simultaneous screening for both studies, i.e. both MAGE-A3 & PRAME expression could be tested on the tumor samples. 10) Japan was added as participating country & an appendix with Japan specific requirements was added. 11) Certain information was updated, e.g. contact numbers for emergency code breaking & SAE reporting, description of the ECOG performance status. |
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18 Oct 2011 |
Amendment 2 included the following changes: 1) After trial initiation, a GS at the tumor site associated with a clinical response to MAGE-A3 ASCI was identified in 2 trials in melanoma and lung cancer. This opens the possibility to identify patients likely to benefit from MAGE-A3 ASCI. To clinically validate these GS biomarkers, DFS analysis in patients presenting the GS was added as co-primary (1ry) objective; 2) At the time of the initially planned 1st interim analysis (IA) there would not have been enough events reported in GS+ population to conclude on relevance of GS selection approach. Clinical validation of GS could only be performed on data set available at time of 2nd IA or final analysis (FA). It was decided to remove 1st efficacy IA; 3) In addition, secondary (2ry) endpoints to evaluate OS & lung-cancer-related survival in GS+ and GS- patients were added; 4) Other 2ry objectives were clarified in accordance with addition of above co-1ry objective; 5) Alpha levels assigned to objectives A and B were adapted to take into account correlation between test statistics for no-CT and overall; 6) A weighted Bonferroni-Holm strategy using the closure principle was put in place in case of efficacy claims at the FA; 7) The Wald test was replaced by Likelihood Ratio test as primary test in Cox models, due to that a slight increase in 1-sided type I error is expected when using an unbalanced design together with Wald test; 8) It was clarified that at time of the analyses, 2-sided p-values will be reported & design considerations adapted using 2-sided significance levels; 9) To validate predictive value of GS, an interaction test between MAGE-A3 ASCI vs placebo & GS status was planned; 10) A new criterion for study treatment postponement to allow recovery of possibly related CTC grade ≥ 2 AEs was added; 11) IDMC responsibilities were modified to accommodate that an independent statistician (vs the sponsor) was to provide the FA for review by the IDMC. |
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06 Jun 2012 |
Protocol Amendment 3 included the following changes: 1) At the European Medicines Agency’s (EMA) request, GSK Biologicals updated its procedure for emergency unblinding during the conduct of a clinical study; 2) According to the revised procedure, the responsibility and the decision to break the treatment code in emergency situations resided solely with the investigator and consequently, the investigator would have full authority to break the treatment code. Wording in the protocol was adapted accordingly; 3) To ensure the availability of images that could be valuable to the accurate assessment of a patient’s disease status, instructions that GSK could collect for review any imaging performed within the scope of this trial and not only images that are related to the identification of recurrences were included; 4) Clarification that at the concluding examination following a recurrence, any tumor assessment performed at the visit showing recurrence did not have to be repeated; 5) Some corrections were made, i.e. footnote cross references, clinical cut off for anti-MAGE-A3 antibodies enzyme-linked immunosorbent assay (ELISA), the power to detect a differential effect in the GS+ population for validation of the gene profile. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
Objective C to demonstrate clinical efficacy in terms of DFS of the MAGE-A3 product versus placebo in NSCLC after complete surgical resection in the GS+ population could not be evaluated as no GS classifier could be identified in the training set. |