Clinical Trial Results:
Expression/DNA methylation of cancer testis antigens may predict response to pembrolizumab in pretreated NSCLC patients
|
Summary
|
|
EudraCT number |
2017-000689-30 |
Trial protocol |
AT |
Global end of trial date |
01 Jun 2022
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
03 Jul 2024
|
First version publication date |
03 Jul 2024
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
Pem-NSCLC
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Medical University of Vienna
|
||
Sponsor organisation address |
Währinger Gürtel 18-20, Wien, Austria, 1090
|
||
Public contact |
Sabine Zoechbauer-Mueller, Med. Univ. Wien, +43 14040073783, sabine.zoechbauer-mueller@meduniwien.ac.at
|
||
Scientific contact |
Sabine Zoechbauer-Mueller, Med. Univ. Wien, +43 14040073783, sabine.zoechbauer-mueller@meduniwien.ac.at
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
06 Oct 2022
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
01 Jun 2022
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The objectives of this study are to determine DNA methylation as well as expression of CTAs in lung adenocarcinoma patients whose tumor cells do express PD-L1 (≥ 1%) as well as in
patients whose tumor cells do not express PD-L1. These results will be compared with the outcome of the patients after treatment with the combination of chemotherapy and
pembrolizumab. In addition, expression of selected CTAs will be investigated in serum samples from these patients.
We hypothesize that in lung adenocarcinomas expression of CTAs may be upregulated by loss of DNA methylation which may result in an enhanced immune response and finally in an
enhanced tumor response and in a better clinical outcome of some patients.
|
||
Protection of trial subjects |
Confidentiality of Data
The investigator affirms that information furnished to the investigator will be maintained in confidence, and such information will be divulged to the institutional review board, ethics review committee (IRB/ERC) or similar or expert committee; affiliated institution and employees, only under an appropriate understanding of confidentiality with such board or committee, affiliated institution and employees. Data generated by this trial will be considered confidential by the investigator, except to the extent that it is included in a publication as provided in the Publications section of this protocol.
Confidentiality of Subject Records
The investigator agrees that IRB/ERC, or regulatory authority representatives may consult and/or copy trial documents in order to verify worksheet/case report form data. By signing the consent form, the subject agrees to this process. If trial documents will be photocopied during the process of verifying worksheet/case report form information, the subject will be identified by unique code only; full names/initials will be masked prior to transmission to the Sponsor.
The investigator agrees to treat all subject data used and disclosed in connection with this trial in accordance with all applicable privacy laws, rules and regulations.
Confidentiality of Investigator Information
The investigator recognizes that certain personal identifying information with respect to the investigator, and all subinvestigators and trial site personnel, may be used and disclosed for trial management purposes, as part of a regulatory submissions, and as required by law. This information may include:
1. name, address, telephone number and e-mail address;
2. hospital or clinic address and telephone number;
3. curriculum vitae or other summary of qualifications and credentials; and
4. other professional documentation.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jun 2018
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Austria: 11
|
||
Worldwide total number of subjects |
11
|
||
EEA total number of subjects |
11
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
3
|
||
From 65 to 84 years |
8
|
||
85 years and over |
0
|
||
|
|||||||
|
Recruitment
|
|||||||
Recruitment details |
Patients with advanced lung adenocarcinoma, without an EGFR mutation or ALK translocation, pretreated with at least 1 platin-based chemotherapy regimen and with by a CT scan documented tumor progression will be included. | ||||||
|
Pre-assignment
|
|||||||
Screening details |
- | ||||||
|
Pre-assignment period milestones
|
|||||||
Number of subjects started |
40 [1] | ||||||
Number of subjects completed |
11 | ||||||
|
Pre-assignment subject non-completion reasons
|
|||||||
Reason: Number of subjects |
Protocol deviation: 29 | ||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: From the 40 pre-assigned patients only 11 could finally be recruited due to protocol deviations. |
|||||||
|
Period 1
|
|||||||
Period 1 title |
Sample collection (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
|
||||||
Blinding used |
Not blinded | ||||||
Blinding implementation details |
In this single-center, phase II, single-arm, open-label study in total 42 patients (21 with ≥ 1% expression of the Programmed Death ligand 1 [PD-L1] on tumor cells and 21 without PD-L1 expression on tumor cells) with advanced NSCLC (adenocarcinoma), without an EGFR mutation or ALK translocation, pretreated with at least 1 platin-based chemotherapy regimen and with by a computertomography (CT) scan documented tumor progression were planned to be included.
|
||||||
|
Arms
|
|||||||
|
Arm title
|
Study | ||||||
Arm description |
In this single-center, phase II, single-arm, open-label study in total 42 patients (21 with ≥ 1% expression of the Programmed Death ligand 1 [PD-L1] on tumor cells and 21 without PD-L1 expression on tumor cells) with advanced NSCLC (adenocarcinoma), without an EGFR mutation or ALK translocation, pretreated with at least 1 platin-based chemotherapy regimen and with by a computertomography (CT) scan documented tumor progression were planned to be included. | ||||||
Arm type |
Active comparator | ||||||
Investigational medicinal product name |
Pembrolizumab
|
||||||
Investigational medicinal product code |
MK-3475
|
||||||
Other name |
|||||||
Pharmaceutical forms |
Infusion
|
||||||
Routes of administration |
Intravenous use
|
||||||
Dosage and administration details |
2 mg/kg Q3W or 200 mg Q3W
|
||||||
|
|||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sample collection
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Study
|
||
Reporting group description |
In this single-center, phase II, single-arm, open-label study in total 42 patients (21 with ≥ 1% expression of the Programmed Death ligand 1 [PD-L1] on tumor cells and 21 without PD-L1 expression on tumor cells) with advanced NSCLC (adenocarcinoma), without an EGFR mutation or ALK translocation, pretreated with at least 1 platin-based chemotherapy regimen and with by a computertomography (CT) scan documented tumor progression were planned to be included. | ||
|
|||||||||
End point title |
CTA methylation [1] | ||||||||
End point description |
|||||||||
End point type |
Primary
|
||||||||
End point timeframe |
2018-2022
|
||||||||
| 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: The study was prematurely stopped and no statistical analysis was calculated. |
|||||||||
|
|||||||||
| Notes [2] - The study was prematurely stopped. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||
End point title |
Treatment response | ||||||||||||||||
End point description |
|||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
2018-2022
|
||||||||||||||||
|
|||||||||||||||||
| Notes [3] - The study was prematurely stopped. |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||
|
Adverse events information [1]
|
|||||||||||
Timeframe for reporting adverse events |
2018-2022
|
||||||||||
Adverse event reporting additional description |
No adverse event reached the 5% threshold.
|
||||||||||
Assessment type |
Systematic | ||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||
Dictionary name |
MedDRA | ||||||||||
Dictionary version |
21
|
||||||||||
|
Reporting groups
|
|||||||||||
Reporting group title |
Study
|
||||||||||
Reporting group description |
No adverse event reached the 5% threshold. | ||||||||||
|
|||||||||||
| 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 adverse event reached the 5% threshold. |
|||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
09 Jul 2019 |
We initially planned to include with chemotherapy pretreated patients with advanced lung adenocarcinoma who received pembrolizumab monotherapy after tumor progression. Since the approval of pembrolizumab monotherapy and the combination of pembrolizumab/platin/pemetrexed by the EMA for the first-line treatment of NSCLC patients with adenocarcinoma subtype the vast majority of patients already receives pembrolizumab in the first line setting. Thus, the number of patients meeting our initial inclusion criteria drastically decreased and we decided to change the study cohort to untreated patients who will receive the EMA approved combination of pembrolizumab/platin/pemetrexed. This change of the project plan was communicated with and approved by Merck, the ethics committee of the Medical University of Vienna and the Austrian Agency for Health and Food Safety. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Challenges were: ineligibility/unwillingness of patients for a tumor re-biopsy; tumor necrosis; SARS-CoV-2 pandemia. | |||
