Clinical Trial Results:
A Phase II open-label multicenter exploratory study to assess efficacy of Pembrolizumab re-challange as second or further line in patients with advanced non - small cell lung cancer
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Summary
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EudraCT number |
2017-003947-39 |
Trial protocol |
ES |
Global end of trial date |
09 Mar 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Feb 2025
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First version publication date |
26 Feb 2025
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Other versions |
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Summary report(s) |
Summary final report_REPLAY REPLAY_PRotocol Summary |
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 |
GECP17/02
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03526887 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Fundación GECP
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Sponsor organisation address |
Avda. Meridiana nº 258, 6th floor, Barcelona, Spain, 08027
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Public contact |
Eva Pereira, Fundación GECP, 34 934302006205, epereira@gecp.org
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Scientific contact |
Eva Pereira, Fundación GECP, 34 934302006205, epereira@gecp.org
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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 |
03 May 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Mar 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Mar 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 |
To evaluate the efficacy of Pembrolizumab re-challenge administered 200 mg iv every 21 days in second or further line for advanced NSCLC after progression to monotherapy check point PD1 / PDL1 inhibitors measured by Overall Response Rate (ORR) per RECIST v1.1 and per modified RECIST (irRC).
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP)
Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jun 2018
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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 |
Spain: 73
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Worldwide total number of subjects |
73
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EEA total number of subjects |
73
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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) |
3
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From 65 to 84 years |
60
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85 years and over |
10
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Recruitment
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Recruitment details |
Between October 2018 and May 2021, a total of 73 patients were enrolled in the study from 17 different sites. | |||||||||
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Pre-assignment
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Screening details |
Patients who are advanced non-small cell lung cancer with prior documented benefit (stable disease, partial response, complete response) in controlling the PD1/PDL1 inhibitor (Nivolumab, Pembrolizumab, Durvalumab, Atezolizumab, Avelumab, or others) during at least 16 weeks will be enrolled in this study. | |||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Experimental: Cohort 1 | |||||||||
Arm description |
Patients who experienced progression disease while on treatment progression disease < 12 weeks after stopping treatment. After that the patients took chemotherapy ≥ 4 cycles and progressed again. After the last progression the patient is included in the study to be retreated with Pembrolizumab 200mg. The treatment will continue until progression, unacceptable toxicity, consent withdraw, or until the treatment is administered during 24 months, whichever occurs first. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Pembrolizumab
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Investigational medicinal product code |
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Other name |
Keytruda
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravascular use
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Dosage and administration details |
All trial treatments will be administered on an outpatient basis.
Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible.
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Arm title
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Experimental: Cohort 2 | |||||||||
Arm description |
Stop treatment and progression > 12 weeks after stopping treatment. After the last progression the patient is included in the study to be retreated with Pembrolizumab 200mg. All trial treatments will be administered on an outpatient basis. Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Pembrolizumab
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Investigational medicinal product code |
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Other name |
Keytruda
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
All trial treatments will be administered on an outpatient basis.
Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible.
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Baseline characteristics reporting groups
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Reporting group title |
Experimental: Cohort 1
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Reporting group description |
Patients who experienced progression disease while on treatment progression disease < 12 weeks after stopping treatment. After that the patients took chemotherapy ≥ 4 cycles and progressed again. After the last progression the patient is included in the study to be retreated with Pembrolizumab 200mg. The treatment will continue until progression, unacceptable toxicity, consent withdraw, or until the treatment is administered during 24 months, whichever occurs first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Experimental: Cohort 2
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Reporting group description |
Stop treatment and progression > 12 weeks after stopping treatment. After the last progression the patient is included in the study to be retreated with Pembrolizumab 200mg. All trial treatments will be administered on an outpatient basis. Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental: Cohort 1
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Reporting group description |
Patients who experienced progression disease while on treatment progression disease < 12 weeks after stopping treatment. After that the patients took chemotherapy ≥ 4 cycles and progressed again. After the last progression the patient is included in the study to be retreated with Pembrolizumab 200mg. The treatment will continue until progression, unacceptable toxicity, consent withdraw, or until the treatment is administered during 24 months, whichever occurs first. | ||
Reporting group title |
Experimental: Cohort 2
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Reporting group description |
Stop treatment and progression > 12 weeks after stopping treatment. After the last progression the patient is included in the study to be retreated with Pembrolizumab 200mg. All trial treatments will be administered on an outpatient basis. Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. | ||
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End point title |
Overall survival | ||||||||||||
End point description |
Overall survival: Defined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.
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End point type |
Primary
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End point timeframe |
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months.
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Statistical analysis title |
Overall Survival | ||||||||||||
Comparison groups |
Experimental: Cohort 1 v Experimental: Cohort 2
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Number of subjects included in analysis |
73
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.016 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Point estimate |
9.7
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
9.4 | ||||||||||||
upper limit |
19.1 | ||||||||||||
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End point title |
Progression Free Survival | ||||||||||||
End point description |
PFS: Defined as the length of time from the date of randomization to the date of the first documented progression of disease. "Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions"
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End point type |
Secondary
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End point timeframe |
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Best Global Response | ||||||||||||||||||||||||
End point description |
To evaluate the best global response of the treatment as measured by investigator-assessed overall response rate (ORR) according to RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
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End point type |
Secondary
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End point timeframe |
From the date of randomization until end of follow up, up to 30 months
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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 |
30 months
30 months
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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 |
19
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Reporting groups
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Reporting group title |
Cohort 1
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Reporting group description |
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Reporting group title |
Cohort 2
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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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18 Jan 2019 |
Change of Sponsor: The Spanish Lung Cancer Group (GECP), sponsor of the REPLAY study, has recently established the GECP Foundation |
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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. | |||
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