Clinical Trial Results:
Neoadjuvant anti PD-1 immunotherapy in resectable non-small cell lung cancer
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Summary
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EudraCT number |
2017-000105-20 |
Trial protocol |
DE |
Global end of trial date |
05 May 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Apr 2025
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First version publication date |
04 Apr 2025
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Other versions |
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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 |
0316-ASG
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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 |
AIO-Studien-gGmbH
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Sponsor organisation address |
Kuno-Fischer-Str. 8, Berlin, Germany, 14057
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Public contact |
Help desk, AIO-Studien-gGmbH, 0049 30814534431, info@aio-studien-ggmbh.de
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Scientific contact |
Help desk, AIO-Studien-gGmbH, 0049 30814534431, info@aio-studien-ggmbh.de
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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 |
05 May 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 May 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
05 May 2023
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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 |
- feasibility and safety of a neoadjuvant application of pembrolizumab
- antitumor activity of pembrolizumab with regard to clinical and pathologic tumor response
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Protection of trial subjects |
This study was planned, analyzed and conducted according to the study protocol and in accordance with the International Conference on Harmonization (ICH) ‚Guideline for Good Clinical Practice E6(R1)‘, CPMP/ICH/135/95, based on the principles of the Declaration of Helsinki (1964) and its October 1996 amendment (Somerset West, South Africa). The study was duly conducted in compliance with the German Arzneimittelgesetz (AMG; German Drug Law), and the corresponding Directive 2001/20/EC. Subjects were fully informed regarding all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Jul 2017
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Long term follow-up planned |
No
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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 |
Germany: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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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) |
23
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening details |
Between 18-Jun-2018 and 03-Feb-2020, 30 patients were recruited into the study. One patient withdrew informed consent prior to treatment start. | ||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Pembrolizumab | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Pembrolizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Study treatment consisted of neoadjuvant pembrolizumab at a dose of 200 mg q3w i.v. for 2 cycles.
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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: One patient was screened and found eligible for study participation, but withdrew consent before treatment start. This patient was removed from all analyses. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pembrolizumab
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Reporting group description |
- | ||
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End point title |
Number of Patients Treated in Compliance With Protocol [1] | ||||||
End point description |
The definition for this endpoint was neoadjuvant pembrolizumab treatment followed by successful curative intent tumor resection.
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End point type |
Primary
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End point timeframe |
From screening until surgery, ca. 6-8 weeks
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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: This was a single-arm exploratory study with a small sample size. No statistical tests were specified. |
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| No statistical analyses for this end point | |||||||
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End point title |
Tumor Response According to RECIST 1.1 Criteria [2] | ||||||||||||||
End point description |
Radiologic tumor assessments for this endpoint were performed at screening and pre-surgery.
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End point type |
Primary
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End point timeframe |
From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
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| Notes [2] - 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: This was a single-arm exploratory study with a small sample size. No statistical tests were specified. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Tumor Response Evaluation - Pathologic Response [3] | ||||||||||||||
End point description |
Pathologic regression grading according to Junker criteria (Junker K, Langner K, Klinke F, Bosse U, Thomas M. Grading of tumor regression in non-small cell lung cancer : morphology and prognosis. Chest 2001; 120:1584-91).
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End point type |
Primary
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End point timeframe |
From screening until surgery, ca. 6-8 weeks
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| Notes [3] - 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: This was a single-arm exploratory study with a small sample size. No statistical tests were specified. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Tumor Response Evaluation - Δ Tumor Size [4] | ||||||||
End point description |
Δ tumor size was defined as the difference [mm] between longest diameter at baseline and pre-surgery.
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End point type |
Primary
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End point timeframe |
From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
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| Notes [4] - 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: This was a single-arm exploratory study with a small sample size. No statistical tests were specified. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Tumor Response - Δ PET Activity [5] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
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| Notes [5] - 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: This was a single-arm exploratory study with a small sample size. No statistical tests were specified. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Disease-free Survival (DFS) at 6 Months | ||||||||
End point description |
Probability DFS was calculated using Kaplan-Meier statistics from date of surgery to the date until tumor recurrence or death. Follow-up was until 24 months after last-patient-out.
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End point type |
Secondary
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End point timeframe |
6 months after surgery, i.e. circa 8 months after treatment start
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| No statistical analyses for this end point | |||||||||
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End point title |
Disease-free Survival (DFS) at 12 Months | ||||||||
End point description |
Probability of disease-free survival (DFS) were calculated from date of surgery until tumor recurrence or death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.
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End point type |
Secondary
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End point timeframe |
12 months after surgery, i.e. circa 14 months after treatment start
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) at 12 Months | ||||||||
End point description |
Probability of overall survival (OS) was calculated from date of surgery until tumor recurrence or death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.
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End point type |
Secondary
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End point timeframe |
12 months after surgery, i.e. circa 14 months after treatment start
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival at 18 Months | ||||||||
End point description |
Probability of overall survival (OS) was calculate from date of surgery until tumor recurrence or death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.
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End point type |
Secondary
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End point timeframe |
18 months after surgery, i.e. circa 20 months after treatment start
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival at 24 Months | ||||||||
End point description |
Probability of overall survival (OS) was calculated from date of surgery until death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.
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End point type |
Secondary
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End point timeframe |
24 months after surgery, i.e. circa 26 months after treatment start
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were reported from the signing of informed consent until the EoT visit, which was scheduled to take place approx. six weeks after surgery.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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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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30 Jan 2019 |
In the inclusion criteria, allowed thresholds for INR and PTT values were reduced to improve suitability of patients regarding surgery. |
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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. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/33529989 |
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