Clinical Trial Results:
Phase II study examining the activity of L19-IL2 immunotherapy and stereotactic ablative radiotherapy in metastatic non-small cell lung cancer
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Summary
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EudraCT number |
2018-002583-11 |
Trial protocol |
FR NL BE GB IT |
Global end of trial date |
06 Jan 2025
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Apr 2026
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First version publication date |
17 Apr 2026
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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 |
UM2018IMMUNOSABR2RLPL
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03705403 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Universiteit Maastricht
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Sponsor organisation address |
Universiteitssingel 40, Maastricht, Netherlands, 6229 ER Maastricht
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Public contact |
Mieke Denys and Berta Ganizada, Sillar Clinical bvba / Maastricht University Precision Medicine, GROW, 32 9395 23 62, berta.ganizada@maastrichtuniversity.nl
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Scientific contact |
Mieke Denys, Philippe Lambin (PI) Berta Ganizada, Sillar Clinical bvba/ Maastricht University Precision Medicine, GROW, 32 9395 23 62, berta.ganizada@maastrichtuniversity.nl
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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 |
30 Jan 2026
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Jan 2025
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Jan 2025
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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 main objective of the trial is to test if the combination of (SAB)R and the immunocytokine L19-IL2 has clinical meaningful activity in patients with limited metastatic non-small cell lung cancer (NSCLC): (≤10 sites, WHO 0-1). The expected activity is a systemic immune response preventing disease progression and resulting in an improvement of progression-free survival (PFS).
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Protection of trial subjects |
Trial subjects were protected by conduct of the study in accordance with the Declaration of Helsinki, ICH-GCP, and applicable national laws and regulations, with prior approval by the relevant Ethics Committees. Patients were informed orally and in writing about the study, its procedures, possible risks and benefits, and written informed consent was obtained before any study-specific procedures were performed. Safety was monitored through AE/SAE/SUSAR reporting and independent DSMB oversight, and subject confidentiality was safeguarded by use of study numbers and restricted access to identifiable data.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Oct 2019
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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 |
Netherlands: 42
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Country: Number of subjects enrolled |
United Kingdom: 3
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Country: Number of subjects enrolled |
Belgium: 32
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Country: Number of subjects enrolled |
France: 8
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Country: Number of subjects enrolled |
Germany: 3
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Worldwide total number of subjects |
88
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EEA total number of subjects |
85
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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) |
41
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From 65 to 84 years |
47
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85 years and over |
0
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Recruitment
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Recruitment details |
88 of 126 planned patients were enrolled. Recruitment closed on 31 December 2023, with the last patient enrolled in January 2024. This was a European multicentre, multinational trial conducted in Belgium, the Netherlands, France, Germany, and the United Kingdom. | |||||||||
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Pre-assignment
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Screening details |
Adults ≥18 years with histologically/cytologically confirmed stage IV metastatic NSCLC, WHO 0–1, adequate organ function and signed consent. Eligible patients had ≤10 metastases (oligo ≤5; poly 6–10), maximum 2 brain metastases with total diameter ≤5 cm, and baseline imaging within 6 weeks before randomisation. | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
88 | |||||||||
Number of subjects completed |
88 | |||||||||
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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 |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
n/a
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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control | |||||||||
Arm description |
Patients received standard of care according to local protocols. In oligometastatic disease, this generally consisted of systemic therapy depending on PD-L1 status, molecular analysis and line of treatment, followed by SABR to all metastatic lesions, with anti-PD(L)1 if standard of care. In poly-metastatic disease, this generally consisted of systemic therapy according to local protocols, with no radiotherapy or radiotherapy/SABR only to symptomatic lesions (maximum 5), with anti-PD(L)1 if standard of care. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Darleukin
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Investigational medicinal product code |
L19-IL2
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Injection
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Dosage and administration details |
The recommended dose turned out to be 15 Mio IU
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Arm title
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Experimental | |||||||||
Arm description |
Oligometastatic patients received SABR to all metastatic lesions followed by up to 6 cycles of L19-IL2. Poly-metastatic patients received SABR or conventional radiotherapy to up to 5 metastatic lesions followed by up to 6 cycles of L19-IL2. Anti-PD(L)1 treatment was allowed if standard of care. | |||||||||
Arm type |
Control | |||||||||
Investigational medicinal product name |
L19 Interleukin-2, Darleukin
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Investigational medicinal product code |
L19-IL2
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion
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Dosage and administration details |
The first administration of L19-IL2 was given within 72 hours of the last irradiation. L19-IL2 was administered at the recommended dose (RD) of 15 Mio IU (fixed dose) on day 1, 3 and 5 each of a 21-day cycle via a 3-hour I.V. infusion started within 72 hours following the completion of SABR, for up to 6 cycles. (I.V.) Drug administration according to the CTCAE version 5 scoring system.
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Baseline characteristics reporting groups
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Reporting group title |
control
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Reporting group description |
Patients received standard of care according to local protocols. In oligometastatic disease, this generally consisted of systemic therapy depending on PD-L1 status, molecular analysis and line of treatment, followed by SABR to all metastatic lesions, with anti-PD(L)1 if standard of care. In poly-metastatic disease, this generally consisted of systemic therapy according to local protocols, with no radiotherapy or radiotherapy/SABR only to symptomatic lesions (maximum 5), with anti-PD(L)1 if standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Experimental
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Reporting group description |
Oligometastatic patients received SABR to all metastatic lesions followed by up to 6 cycles of L19-IL2. Poly-metastatic patients received SABR or conventional radiotherapy to up to 5 metastatic lesions followed by up to 6 cycles of L19-IL2. Anti-PD(L)1 treatment was allowed if standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full trial analysis
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomised subjects, analysed according to the treatment arm to which they were randomised, regardless of treatment received, protocol deviations, or early discontinuation.
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End points reporting groups
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Reporting group title |
control
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Reporting group description |
Patients received standard of care according to local protocols. In oligometastatic disease, this generally consisted of systemic therapy depending on PD-L1 status, molecular analysis and line of treatment, followed by SABR to all metastatic lesions, with anti-PD(L)1 if standard of care. In poly-metastatic disease, this generally consisted of systemic therapy according to local protocols, with no radiotherapy or radiotherapy/SABR only to symptomatic lesions (maximum 5), with anti-PD(L)1 if standard of care. | ||
Reporting group title |
Experimental
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Reporting group description |
Oligometastatic patients received SABR to all metastatic lesions followed by up to 6 cycles of L19-IL2. Poly-metastatic patients received SABR or conventional radiotherapy to up to 5 metastatic lesions followed by up to 6 cycles of L19-IL2. Anti-PD(L)1 treatment was allowed if standard of care. | ||
Subject analysis set title |
Full trial analysis
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All randomised subjects, analysed according to the treatment arm to which they were randomised, regardless of treatment received, protocol deviations, or early discontinuation.
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End point title |
Progression-free survival (PFS) | ||||||||||||
End point description |
Progression-free survival (PFS) at 1.5 years after randomisation. PFS was defined as the time from randomisation to documented disease progression according to RECIST 1.1 or death due to any cause.
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End point type |
Primary
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End point timeframe |
up to 1.5 years after randomisation
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Attachments |
Untitled (Filename: Post database_primary outcomes Stat analysis.pdf) |
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Statistical analysis title |
Statistical analysis of progression free survival | ||||||||||||
Comparison groups |
control v Experimental
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
= 0.15 [2] | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.66
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
0.4 | ||||||||||||
upper limit |
1.08 | ||||||||||||
Variability estimate |
Standard error of the mean
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| Notes [1] - Pre-specified primary survival analysis of PFS and OS per SAP using Kaplan–Meier, log-rank, and adjusted Cox proportional hazards models. [2] - Between-arm comparison for progression-free survival using log-rank test; not statistically significant. |
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End point title |
Overall survival (OS) | ||||||||||||
End point description |
Overall survival (OS) at 5 years after randomisation. OS was defined as the time between randomisation and death. Patients still alive at the last follow-up were censored. OS was estimated by Kaplan-Meier analysis and compared between treatment arms using a log-rank test.
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End point type |
Secondary
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End point timeframe |
Up to 5 years after randomisation
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Attachments |
Untitled (Filename: Post database_primary outcomes Stat analysis.pdf) |
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Statistical analysis title |
Statistical analysis of overall survival | ||||||||||||
Comparison groups |
control v Experimental
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||
P-value |
= 0.19 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
- | ||||||||||||
upper limit |
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Variability estimate |
Standard error of the mean
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| Notes [3] - Pre-specified superiority analysis of overall survival comparing experimental versus control, using Kaplan–Meier survival analysis with log-rank testing and multivariable Cox proportional hazards modelling adjusted for histology and disease type, with centre included as a random effect. |
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Adverse events information
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Timeframe for reporting adverse events |
Between January 2020 and January 2024
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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 |
29
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Reporting groups
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Reporting group title |
Experimental
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Reporting group description |
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Reporting group title |
Control
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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? No | |||
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/32539805 http://www.ncbi.nlm.nih.gov/pubmed/3253980 http://www.ncbi.nlm.nih.gov/pubmed/33137396 http://www.ncbi.nlm.nih.gov/pubmed/33693966 http://www.ncbi.nlm.nih.gov/pubmed/3328527 http://www.ncbi.nlm.nih.gov/pubmed/35701415 |
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