Clinical Trial Results:
A randomised, double blind phase I/II trial to investigate efficacy, immunogenicity and safety of intradermally administered BI 1361849 (CV9202) plus afatinib versus placebo plus afatinib as first-line treatment for patients with stage IV adenocarcinoma of the lung harbouring common EGFR mutations.
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Summary
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EudraCT number |
2015-001477-41 |
Trial protocol |
ES DE |
Global end of trial date |
20 Jun 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jan 2019
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First version publication date |
06 Jan 2019
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Other versions |
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Summary report(s) |
Statement |
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 |
1373.1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Boehringer Ingelheim
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Sponsor organisation address |
Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
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Public contact |
QRPE Processes and Systems Coordination, Clinical Trial
Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.com
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Scientific contact |
QRPE Processes and Systems Coordination, Clinical Trial
Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.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 |
20 Jun 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Jun 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Jun 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate efficacy, immunogenicity and safety of BI 1361849 (CV9202) in combination with afatinib as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) (stage IV) harbouring common Epidermal Growth Factor Receptor (EGFR) mutations.
Phase I: To confirm feasibility and safety of the combination of BI 1361849 (CV9202) with afatinib, and to assess immunological responses of BI 1361849 (CV9202) in combination with afatinib in comparison to placebo plus afatinib.
Phase II (analyses will cover all randomised patients, i.e. will also include all patients randomised during the phase I part of the trial): To assess efficacy, immunogenicity and safety of BI 1361849 (CV9202) in combination with afatinib in comparison to placebo plus afatinib.
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Protection of trial subjects |
No patient entered the study, therefore no results data available. 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entering the trial. 199998 number entered in population of trial subjects is "Not applicable", the number is added to match the count in the participant flow which we get after adding the NA value "99999" for each treatment arm.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Jun 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
United Kingdom: 199998
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Worldwide total number of subjects |
199998
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EEA total number of subjects |
199998
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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) |
199998
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
No patient was entered in the trial. | |||||||||
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Pre-assignment
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Screening details |
All patients were planned to be screened for eligibility to participate in the trial. Patients had to attend specialist sites which would then ensure that they (the patients) met all inclusion/exclusion criteria. Patients were not to be entered to the trial if any one of the specific entry criteria were violated. | |||||||||
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Period 1
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Period 1 title |
Treatment 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, Assessor | |||||||||
Blinding implementation details |
Placebo-controlled, double blind, randomised, parallel design
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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BI 1361849 (CV9202) in combination with afatinib | |||||||||
Arm description |
Patients were to be administered with BI 1361849 (CV9202) 0.32 milligram (mg) via intradermal injection per each of 6 components (i.e. 1.92 mg in total) per vaccination time point on day 1 of weeks 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, and continued thereafter every 6 weeks; 2 injections per component resulting in 12 intradermal injections per vaccination visit distributed over 4 different body sites (upper arms, thighs) with afatinib: 40 mg once daily orally (dose can be reduced to 30 mg and 20 mg daily) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
BI 1361849
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
Patients were to be administered with BI 1361849 (CV9202) 0.32 milligram (mg) via intradermal injection per each of 6 components (i.e. 1.92 mg in total) per vaccination time point on day 1 of weeks 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, and continued thereafter every 6 weeks; 2 injections per component resulting in 12 intradermal injections per vaccination visit distributed over 4 different body sites (upper arms, thighs)
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Investigational medicinal product name |
afatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients were to be administered with afatinib 40 mg once daily orally (dose can be reduced to 30 mg and 20 mg daily)
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Arm title
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Placebo matching BI 1361849 (CV9202) in combination with afati | |||||||||
Arm description |
Patients were to be administered with placebo matching BI 1361849 (CV9202) via intradermal injection per each of 6 components per vaccination time point on day 1 of weeks 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, and continued thereafter every 6 weeks; 2 injections per component resulting in 12 intradermal injections per vaccination visit distributed over 4 different body sites (upper arms, thighs) with afatinib: 40 mg once daily orally (dose can be reduced to 30 mg and 20 mg daily) | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo matching BI 1361849
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
Patients were to be administered with placebo matching BI 1361849 (CV9202) via intradermal injection per each of 6 components per vaccination time point on day 1 of weeks 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, and continued thereafter every 6 weeks; 2 injections per component resulting in 12 intradermal injections per vaccination visit distributed over 4 different body sites (upper arms, thighs)
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Investigational medicinal product name |
afatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients were to be administered with afatinib 40 mg once daily orally (dose can be reduced to 30 mg and 20 mg daily)
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Baseline characteristics reporting groups
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Reporting group title |
BI 1361849 (CV9202) in combination with afatinib
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Reporting group description |
Patients were to be administered with BI 1361849 (CV9202) 0.32 milligram (mg) via intradermal injection per each of 6 components (i.e. 1.92 mg in total) per vaccination time point on day 1 of weeks 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, and continued thereafter every 6 weeks; 2 injections per component resulting in 12 intradermal injections per vaccination visit distributed over 4 different body sites (upper arms, thighs) with afatinib: 40 mg once daily orally (dose can be reduced to 30 mg and 20 mg daily) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo matching BI 1361849 (CV9202) in combination with afati
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Reporting group description |
Patients were to be administered with placebo matching BI 1361849 (CV9202) via intradermal injection per each of 6 components per vaccination time point on day 1 of weeks 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, and continued thereafter every 6 weeks; 2 injections per component resulting in 12 intradermal injections per vaccination visit distributed over 4 different body sites (upper arms, thighs) with afatinib: 40 mg once daily orally (dose can be reduced to 30 mg and 20 mg daily) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BI 1361849 (CV9202) in combination with afatinib
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Reporting group description |
Patients were to be administered with BI 1361849 (CV9202) 0.32 milligram (mg) via intradermal injection per each of 6 components (i.e. 1.92 mg in total) per vaccination time point on day 1 of weeks 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, and continued thereafter every 6 weeks; 2 injections per component resulting in 12 intradermal injections per vaccination visit distributed over 4 different body sites (upper arms, thighs) with afatinib: 40 mg once daily orally (dose can be reduced to 30 mg and 20 mg daily) | ||
Reporting group title |
Placebo matching BI 1361849 (CV9202) in combination with afati
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Reporting group description |
Patients were to be administered with placebo matching BI 1361849 (CV9202) via intradermal injection per each of 6 components per vaccination time point on day 1 of weeks 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, and continued thereafter every 6 weeks; 2 injections per component resulting in 12 intradermal injections per vaccination visit distributed over 4 different body sites (upper arms, thighs) with afatinib: 40 mg once daily orally (dose can be reduced to 30 mg and 20 mg daily) | ||
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End point title |
Progression free survival (PFS) [1] | ||||||||||||
End point description |
Progression free survival (PFS), defined as time (days) from the date of randomisation to the date of progression or to the date of death, whichever occurs first. This will be centrally adjudicated by independent review according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1). 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entered in the trial.
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End point type |
Primary
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End point timeframe |
From the date of randomisation to the date of progression or to the date of death
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No participant entered in the trial hence results are not available. |
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| Notes [2] - Treated Set [3] - Treated Set |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall Survival (OS) | ||||||||||||
End point description |
Overall survival (OS), defined as time (days) from the date of randomisation to the date of death. 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entered in the trial.
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End point type |
Secondary
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End point timeframe |
From the date of randomisation to the date of death.
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| Notes [4] - Treated Set [5] - Treated Set |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
PFS status at 52 weeks after randomisation by central independent review based on RECIST 1.1 | ||||||||||||
End point description |
Progression free survival (PFS) status at 52 weeks, defined as time (days) from the date of randomisation to the date of progression or to the date of death or week 52, whichever occurs first. This will be centrally adjudicated by independent review according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1). 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entered in the trial.
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End point type |
Secondary
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End point timeframe |
At 52 weeks after randomisation
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| Notes [6] - Treated Set [7] - Treated Set |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Progression free survival 2 (PFS2) | ||||||||||||
End point description |
PFS2, defined as time (days) from randomisation to either death or disease progression by investigator assessment occurring after initiation of 1st subsequent post trial systemic therapy. 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entered in the trial.
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End point type |
Secondary
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End point timeframe |
From randomisation to either death or disease progression by investigator assessment occurring after initiation of 1st subsequent post trial systemic therapy
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| Notes [8] - Treated Set [9] - Treated Set |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Immune response status | |||||||||
End point description |
A planned total amount of approx. 330 ml blood will be taken within a planned time of week 13 in all 120 patients for the purpose of immunomonitoring at time points before start of treatment (C1V1) as well as at planned time points week 6 (C2V1) and week 13 (C3V2) after the first vaccination. Patients are considered to show an immune response against BI 1361849 (CV9202) if at least one of the two post-baseline time points, week 6 and 13, show assay positivity for at least one of the assessments by Intracellular Cytokine Staining (ICS), Enzyme-linked immunosorbent spot (ELISpot) or Enzyme-linked immunosorbent assay (ELISA) for at least one of the six antigens. 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entered in the trial.
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End point type |
Secondary
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End point timeframe |
Week 6 and 13
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| Notes [10] - Treated Set [11] - Treated Set |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Symptomatic progression | ||||||||||||
End point description |
Symptomatic progression, defined as time (days) from randomisation to an increase of at least 10 points from baseline for one or more of cough (Q1, QLQ-LC13), dyspnoea (Q3-5, QLQ-LC13) or chest pain (Q10, QLQLC13) based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung cancer specific supplementary module (EORTC QLQ-LC13). 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entered in the trial.
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End point type |
Secondary
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End point timeframe |
From randomisation to an increase of at least 10 points from baseline for one or one or more of cough (Q1, QLQ-LC13), dyspnea (Q3-5, QLQ-LC13) or chest pain (Q10, QLQ-LC13)
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| Notes [12] - Treated Set [13] - Treated Set |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Discontinuation of vaccination by 13 weeks after randomisation due to an adverse event or patient refusal to continue taking medication | |||||||||
End point description |
Discontinuation of vaccination by 13 weeks after randomisation due to an adverse event or patient refusal to continue taking medication. This was planned to analyse at the primary analysis, planned at 52 weeks after the last patient has been randomised. It was planned to analyse separately for all randomised patients from phase I, and all randomised patients across both phase I and phase II portions of the trial. 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entered in the trial.
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End point type |
Secondary
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End point timeframe |
At 52 weeks after the last patient has been randomised
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| Notes [14] - Treated Set [15] - Treated Set |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Discontinuation of vaccination by 24 weeks after randomisation due to an adverse event or patient refusal to continue taking medication | |||||||||
End point description |
Discontinuation of vaccination by 24 weeks after randomisation due to an adverse event or patient refusal to continue taking medication. This was planned to analyse at the primary analysis, planned at 52 weeks after the last patient has been randomised. 99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants entered in the trial.
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End point type |
Secondary
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End point timeframe |
At 52 weeks after the last patient has been randomized
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| Notes [16] - Treated Set [17] - Treated Set |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
All adverse events occurring after first intake of treatment until end of the follow up period.
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Adverse event reporting additional description |
99999 is "Not applicable" value or 0 participants, this trial was discontinued with no participants enrolled in the trial.
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
0
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| Frequency threshold for reporting non-serious adverse events: 5% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No participant entered in the trial hence results are not available. |
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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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26 Aug 2015 |
Administrative changes, corrections, clarifications and re-wording , Added missed vital signs at week 13, Added Electrocardiogram (ECG ) at time points before start of treatment and change frequency of ECG from every second course to every course, Added clarification on Peripheral Blood Mononuclear Cells blood collection, Specified that pneumonitis will be ruled out with a high-resolution chest Computed tomography (CT) rather than x-ray/low dose CT, Removed bands and change to perform Prothrombin Time or International Normalised Ratio in safety laboratory parameters and Added Data Monitoring Committee review of safety data after the first 20 patients have been treated before originally planned review after the first 40 patients have been treated. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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. | |||
| This trial was discontinued with no participants enrolled in the trial. | |||
