Clinical Trial Results:
A phase II open-label study of Atezolizumab in combination with bevacizumab as first line treatment for locally advanced or metastatic high-intermediate tumour mutation burden (TMB) selected non-squamous non-small cell lung cancer (NSCLC) patients
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Summary
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EudraCT number |
2018-004654-17 |
Trial protocol |
ES |
Global end of trial date |
16 Oct 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Apr 2026
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First version publication date |
11 Apr 2026
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Other versions |
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Summary report(s) |
CSR summary TELMA |
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 |
GECP18/03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03836066 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Roche Code: ML40237 | ||
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Sponsors
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Sponsor organisation name |
Fundación GECP
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Sponsor organisation address |
Avenida Meridiana 358 6º planta, Barcelona, Spain,
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Public contact |
Maria Fernández, Fundación GECP, +34 934302006, secretaria@gecp.org
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Scientific contact |
Mariano Provencio, Fundación GECP, +34 934302006, mprovencio@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 |
06 Jun 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Oct 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Oct 2024
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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 Atezolizumab in combination with Bevacizumab as measured by Progression Free Survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
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Protection of trial subjects |
Not applicable
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Background therapy |
Atezolizumab is a humanized anti-PD-L1 monoclonal antibody that inhibits its interaction with its receptors, PD-1 and B7.1 (CD80, B7-1), reinvigorating anticancer immunity. The OAK study evaluated the efficacy of Atezolizumab compared to Docetaxel in 1.225 patients previously treated with locally-advanced or metastatic NSCLC. The PD-L1 targeted therapy by Atezolizumab resulted in a clinically relevant improvement of overall survival versus Docetaxel regardless of PD-L1 expression or histology, with a favourable safety profile. The median OS in this study was 13.8 months (95% CI 11.8-15.7) in the Atezolizumab arm compared to 9.6 months (95% CI 8.6-11.2) in the Docetaxel arm (HR=0.73, 95% CI 0.62-0.87; p=0.0003). Bevacizumab is a recombinant, humanized therapeutic anti-VEGF antibody that inhibits tumor angiogenesis which may correct the immunosuppressive function exerted by VEGF, increasing the infiltration of T effector cells in cancer. The phase 3 study of Atezolizumab in combination with Bevacizumab compared to Sunitinib single agent (IMmotion151), as first-line therapy in untreated metastatic Renal Cell Carcinoma (RCC) patients. This clinical trial showed a significant benefit of 3.5 months in the PFS favouring the CIT-Bevacizumab combination (11.2 m vs. 7.7 m) with a tolerable safety profile in PD-L1+ patients19. These data confirm the role of Bevacizumab as an immune modulating agent that may provide a successful combination strategy in different tumor types. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
17 Jul 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 |
Spain: 38
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Worldwide total number of subjects |
38
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EEA total number of subjects |
38
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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) |
19
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From 65 to 84 years |
19
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85 years and over |
0
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Recruitment
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Recruitment details |
Population: stage IIIB - IV non-squamous selected high-intermediate tumor mutation burden (TMB) non-small cell lung cancer patients. This is an open-label, non-randomized, phase II, multi-centre clinical trial. | ||||||
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Pre-assignment
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Screening details |
Chemotherapy-naïve patients high-intermediate TMB (TMB≥10 mutations/MB analyzed in tumor or TMB≥16 mutations/MB analyzed in blood) and with locally advanced or metastatic non-squamous non-small cell lung cancer patients will be selected. | ||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not blinded
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Arms
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Arm title
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One Arm | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Atezolizumab
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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 |
see study protocol
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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 |
One Arm
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Reporting group description |
- | ||
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End point title |
Progression Free Survival (PFS) at 12 months [1] | ||||||||
End point description |
To evaluate the efficacy of Atezolizumab in combination with Bevacizumab as measured by Progression Free Survival (PFS) at 12 months according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
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End point type |
Primary
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End point timeframe |
From inclusion date to date of progression
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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: The statistical analysis for an endpoint is not mandatory. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Response Rate | ||||||||
End point description |
ORR results displays the best percentage change from baseline in the sum of target lesion diameters for each evaluable patient, categorized by radiological response
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End point type |
Secondary
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End point timeframe |
at CT-scan evaluation
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival | ||||||||
End point description |
NA
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End point type |
Secondary
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End point timeframe |
From inclusion to last follow up or date of death
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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 |
An AE is defined as any untoward medical occurrence that occurs from the subject’s written consent to participate in the study through 30 days after the final administration of the IMP
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Adverse event reporting additional description |
After informed consent has been obtained, but prior to initiation of study drug, only serious adverse events caused by a protocol-mandated intervention (e.g., invasive procedures such as biopsies, discontinuation of medications) should be reported.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5.0
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
All subjets | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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24 Jan 2020 |
Adminsitrative changes in the protocol (correction of typos and a few wording corrections) |
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13 Jul 2020 |
Added in the protocol de determination of the TMB in blood per foundation One |
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14 Dec 2020 |
Update of the sample size |
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28 Jan 2022 |
Update of the pharmacogenmic studies in the study samples |
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08 Jul 2024 |
amendment to the protocol to transfer patients still on treatment to a PTAP program |
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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/36520426 |
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