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Non-small Cell Lung Cancer (NSCLC)EXPLORENCT07900581

Analysis of Whole Exome and Transcriptome Sequencing to Identify Prognostic Biomarkers in Patients With Non-Small Cell Lung Cancer (NSCLC)

An observational study of Non-small Cell Lung Cancer (NSCLC), run by Hellenic Cooperative Oncology Group at 20 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a non-interventional translational research study aiming to comprehensively characterize the genomic and transcriptomic landscape of patients with non-small cell lung cancer (NSCLC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer (NSCLC)
How many people
300 participants
Where
20 sitesin 2 countries
Study dates
11 Dec 2021to 31 Dec 2026
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: The EXPLORE study will enroll approximately 300 patients with histologically confirmed Non-Small Cell Lung Cancer (NSCLC) who have received immunotherapy as part of standard care. Participants will provide tumor tissue, either formalin-fixed paraffin-embedded (FFPE) blocks or fresh-frozen samples, along with peripheral blood samples for germline DNA analysis. Tissue samples will be used for Whole Exome Sequencing (WES) and RNA sequencing (RNA-seq), enabling comprehensive characterization of genomic alterations, transcriptomic profiles, tumor mutational burden, and immune-related features. A sub-study will include approximately 20 patients with unresectable stage III NSCLC receiving concurrent chemoradiation (cCRT) followed by Durvalumab maintenance according to standard of care. For these patients, longitudinal blood samples will be collected at baseline (pre-cCRT) and at multiple timepoints during Durvalumab treatment to evaluate circulating tumor DNA (ctDNA) dynamics, minimal

Main Study:

Diagnosis: Histologically confirmed Non-Small Cell Lung Cancer (NSCLC). Age: ≥18 years. Consent: Signed informed consent for participation in the study.

Patient Cohorts:

Metastatic NSCLC (Stage IV): 150 patients. Must have received immunotherapy from the date of study amendment. Early-stage NSCLC (Stage I-IIIB): 150 patients. Must have received immunotherapy from the date of study amendment. At least 50 patients must be resectable (Stages I, II, selected Stage III) and treated with adjuvant immunotherapy.

Biological Material:

Availability of FFPE tumor tissue collected ≤6 months before study entry. Availability of peripheral blood for germline DNA extraction. Molecular Analysis: Sufficient DNA and RNA for Whole Exome Sequencing (WES) and RNA sequencing (RNA-seq).

Sub - Study:

Participants must be enrolled in the main EXPLORE study. Diagnosis: Histologically confirmed, unresectable Stage III NSCLC. Treatment Plan: Scheduled to receive concurrent chemoradiation (cCRT) followed by Durvalumab maintenance as per standard of care.

Age: ≥18 years. Consent: Signed informed consent for ctDNA sub-study participation. Biospecimens: Willingness to provide longitudinal blood samples (baseline, during Durvalumab cycles, per protocol).

Trial locations and contacts

20 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Elefteria Tsolaki contact

+30 21 0691 2520

hecogoff@otenet.gr

20 sites in 2 countries

Greece19 sites, 19 recruiting

  • Euroclinic Athens

    Athens, 115 21

    Christos Panopoulos, +30 21 0641 6600, chris.panopoulos@gmail.com

    Christos Panopoulos

    Recruiting

  • 401 General Military Hospital of Athens

    Athens, 115 25

    Nikolaos Tsoukalas, +30 21 0749 4000, tsoukn@yahoo.gr

    Nikolaos Tsoukalas

    Recruiting

  • Henry Dunant Hospital Center

    Athens, 115 26

    Ioannis Mountzios, +30 21 0697 2000, gmountzios@gmail.com

    Ioannis Mountzios

    Recruiting

  • Alexandra General Hospital

    Athens, 115 28

    Flora Zagouri, +30 21 0338 1100, florazagouri@yahoo.co.uk

    Flora Zagouri

    Recruiting

  • Alexandra General Hospital

    Athens, 115 28

    Michael Liontos, +30 21 0338 1100, mliontos@gmail.com

    Michael Liontos

    Recruiting

  • Attikon University General Hospital

    Athens, 124 62

    Amanda Psyrri, +30 21 0583 1000, psyrri237@yahoo.com

    Amanda Psyrri

    Recruiting

  • General Oncology Hospital Agioi Anargyroi

    Athens, 145 64

    Joseph Sgouros, +30 21 0350 1500, josephsgouros@yahoo.co.uk

    Joseph Sgouros

    Recruiting

  • HYGEIA Hospital

    Athens, 151 23

    Evaggelia Razis, +30 21 0686 7000, erazis@hygeia.gr

    Evaggelia Razis

    Recruiting

  • HYGEIA Hospital

    Athens, 151 23

    Paraskevas Kosmidis, +30 21 0686 7000, parkosmi@otenet.gr

    Paraskevas Kosmidis

    Recruiting

  • MITERA Private Hospital

    Athens, 151 23

    Adamantia Nikolaidi, +30 21 0686 9000, mantonikolaidi@gmail.com

    Adamantia Nikolaidi

    Recruiting

  • 2nd Oncology Department, Metropolitan Hospital

    Athens, 185 47

    Epameinontas Samantas, +30 21 0480 9000, epsam@otenet.gr

    Epameinontas Samantas

    Recruiting

  • 4th Oncology Department, Metropolitan Hospital

    Athens, 185 47

    Helena Linardou, +30 21 0480 9000, elinardou@icloud.com

    Helena Linardou

    Recruiting

  • Kavala General Hospital

    Kavala, 654 03

    Anastasios Vagionas, +30 251 350 1100, tvagionas@yahoo.com

    Anastasios Vagionas

    Recruiting

  • General Hospital Agios Andreas

    Pátrai, 263 32

    Athina Christopoulou, +30 261 360 1000, athinachristo@hotmail.com

    Athina Christopoulou

    Recruiting

  • University General Hospital of Patras

    Pátrai, 265 04

    Foteinos-Ioannis Dimitrakopoulos, +30 261 360 3000, fodimitrakopoulos@upatras.gr

    Foteinos-Ioannis Dimitrakopoulos

    Recruiting

  • THEAGENIO Anti-Cancer Hospital of Thessaloniki

    Thessaloniki, 546 39

    Anastasios Boutis, +30 231 330 1111, alboutis@otenet.gr

    Anastasios Boutis

    Recruiting

  • Euromedica General Clinic

    Thessaloniki, 546 45

    Charisios Karanikiotis, +30 231 089 5100, hkaranik@icloud.com

    Charisios Karanikiotis

    Recruiting

  • Saint Luke's Clinic

    Thessaloniki, 552 36

    Elena Fountzilas, +30 2310 380 000, elenafou@gmail.com

    Elena Fountzilas

    Recruiting

  • Thessaloniki General Hospital "George Papanikolaou"

    Thessaloniki, 570 10

    Sofia Lampaki, +30 231 330 7000, sofialampaki@yahoo.gr

    Sofia Lampaki

    Recruiting

Other trials in Greece

Cyprus1 site, 1 recruiting

  • German Oncology Center

    Limassol, 4108

    Elefterios Vorrias, +357 25 208000, eleftherios.vorrias@goc.com.cy

    Elefterios Vorrias

    Recruiting

Other trials in Cyprus

About this study

Official title: Whole Exome and Transcriptome Sequencing Analysis for the Identification of Prognostic Biomarkers in Patients With Non-Small Cell Lung Cancer (NSCLC) - Hellenic Cooperative Oncology Group (HeCOG)

This is a non-interventional translational research study aiming to comprehensively characterize the genomic and transcriptomic landscape of patients with non-small cell lung cancer (NSCLC). The study will employ whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on tumor tissue samples and matched germline DNA to identify genomic alterations, mutational signatures, and transcriptomic profiles associated with prognosis and response to immunotherapy.

A total of approximately 300 patients with histologically confirmed NSCLC will be included, comprising both metastatic and early-stage disease. Formalin-fixed paraffin-embedded (FFPE) tumor tissue and, where available, fresh frozen samples will be analyzed. Peripheral blood samples will also be collected for germline DNA assessment. The study aims to identify clinically actionable genomic alterations, measure tumor mutational burden (TMB), characterize immune-related gene expression signatures, and investigate associations between molecular findings and clinical outcomes.

Read more

In addition, a pilot sub-study will evaluate circulating tumor DNA (ctDNA) dynamics in approximately 20 patients with unresectable stage III NSCLC treated with concurrent chemoradiation followed by durvalumab maintenance therapy. Longitudinal plasma samples will be collected at predefined timepoints to assess minimal residual disease (MRD), ctDNA kinetics, and correlations with clinical outcomes including progression-free survival (PFS) and overall survival (OS).

The results of this study are expected to improve understanding of tumor biology and immune landscape in NSCLC and support the identification of prognostic and predictive biomarkers for immunotherapy and other treatment strategies.

Keywords
Whole Exome Sequencing, Immunotherapy, Biomarkers, ctDNA
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07900581
Study groupRoleWhat they receive
Patients with histologically confirmed non-small cell lung.Patients with histologically confirmed non-small cell lung cancer providing tumor tissue and blood samples for genomic and transcriptomic analyses, including whole-exome sequencing, RNA sequencing, and ctDNA analysis in a subset of patients.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prevalence of genomic alterations, TMB levels, and mRNA-based immune subtypes

    Percentage of Greek NSCLC patients presenting with specific oncogenic drivers, clinically actionable mutations, germline pathogenic/likely pathogenic variants, Tumor Mutational Burden (TMB) signatures, and distinct transcriptomic mRNA-based immune subtypes.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2026
  2. Study start11 Dec 2021
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07900581
Sponsor's protocol ID
ΗΕTR2/22
Acronym
EXPLORE
Status last verified
Apr 2026
First submitted
21 Oct 2026
Last updated
28 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. doi: 10.1200/JCO.18.00149. Epub 2019 Jan 8.

    PubMed 30620668

  • Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodriguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):491-503. doi: 10.1056/NEJMoa2302983. Epub 2023 Jun 3.

    PubMed 37272513

  • Felip E, Altorki N, Zhou C, Vallieres E, Martinez-Marti A, Rittmeyer A, Chella A, Reck M, Goloborodko O, Huang M, Belleli R, McNally V, Srivastava MK, Bennett E, Gitlitz BJ, Wakelee HA. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023 Oct;34(10):907-919. doi: 10.1016/j.annonc.2023.07.001. Epub 2023 Jul 17.

    PubMed 37467930

  • Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.

    PubMed 35403841

  • Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.

    PubMed 28885881

  • Ning Z, Cox AJ, Mullikin JC. SSAHA: a fast search method for large DNA databases. Genome Res. 2001 Oct;11(10):1725-9. doi: 10.1101/gr.194201.

    PubMed 11591649

  • Li H. Exploring single-sample SNP and INDEL calling with whole-genome de novo assembly. Bioinformatics. 2012 Jul 15;28(14):1838-44. doi: 10.1093/bioinformatics/bts280. Epub 2012 May 7.

    PubMed 22569178

  • Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009 Jul 15;25(14):1754-60. doi: 10.1093/bioinformatics/btp324. Epub 2009 May 18.

    PubMed 19451168

  • Pietrzak M, Papp A, Curtis A, Handelman SK, Kataki M, Scharre DW, Rempala G, Sadee W. Gene expression profiling of brain samples from patients with Lewy body dementia. Biochem Biophys Res Commun. 2016 Oct 28;479(4):875-880. doi: 10.1016/j.bbrc.2016.09.114. Epub 2016 Sep 22.

    PubMed 27666482

  • Fountzilas E, Kotoula V, Koliou GA, Liontos M, Papadopoulou K, Giannoulatou E, Papanikolaou A, Tikas I, Chrisafi S, Mauri D, Chatzopoulos K, Fostira F, Pectasides D, Oikonomopoulos G, Aivazi D, Andrikopoulou A, Visvikis A, Aravantinos G, Zagouri F, Fountzilas G. Tumor Genotyping and Homologous Recombination Repair Gene Variants in Patients With Epithelial Ovarian Cancer: Is Pathogenic Enough? Front Oncol. 2021 Jun 1;11:683057. doi: 10.3389/fonc.2021.683057. eCollection 2021.

    PubMed 34141624

  • Fountzilas E, Kotoula V, Koliou GA, Giannoulatou E, Gogas H, Papadimitriou C, Tikas I, Zhang J, Papadopoulou K, Zagouri F, Christodoulou C, Koutras A, Makatsoris T, Chrisafi S, Linardou H, Varthalitis I, Papatsibas G, Razis E, Papakostas P, Samantas E, Aravantinos G, Bafaloukos D, Kosmidis P, Koumarianou A, Psyrri A, Pentheroudakis G, Pectasides D, Futreal A, Fountzilas G, Tsimberidou AM. Pathogenic mutations and overall survival in 3,084 patients with cancer: the Hellenic Cooperative Oncology Group Precision Medicine Initiative. Oncotarget. 2020 Jan 7;11(1):1-14. doi: 10.18632/oncotarget.27338. eCollection 2020 Jan 7.

    PubMed 32002119

  • Fountzilas G, Giannoulatou E, Alexopoulou Z, Zagouri F, Timotheadou E, Papadopoulou K, Lakis S, Bobos M, Poulios C, Sotiropoulou M, Lyberopoulou A, Gogas H, Pentheroudakis G, Pectasides D, Koutras A, Christodoulou C, Papandreou C, Samantas E, Papakostas P, Kosmidis P, Bafaloukos D, Karanikiotis C, Dimopoulos MA, Kotoula V. TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer treated in the adjuvant setting. Oncotarget. 2016 May 31;7(22):32731-53. doi: 10.18632/oncotarget.9022.

    PubMed 27129168

  • Ricciuti B, Recondo G, Spurr LF, Li YY, Lamberti G, Venkatraman D, Umeton R, Cherniack AD, Nishino M, Sholl LM, Shapiro GI, Awad MM, Cheng ML. Impact of DNA Damage Response and Repair (DDR) Gene Mutations on Efficacy of PD-(L)1 Immune Checkpoint Inhibition in Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 Aug 1;26(15):4135-4142. doi: 10.1158/1078-0432.CCR-19-3529. Epub 2020 Apr 24.

    PubMed 32332016

  • Ji W, Weng X, Xu D, Cai S, Lou H, Ding L. Non-small cell lung cancer cells with deficiencies in homologous recombination genes are sensitive to PARP inhibitors. Biochem Biophys Res Commun. 2020 Jan 29;522(1):121-126. doi: 10.1016/j.bbrc.2019.11.050. Epub 2019 Nov 18.

    PubMed 31753490

  • Heeke AL, Pishvaian MJ, Lynce F, Xiu J, Brody JR, Chen WJ, Baker TM, Marshall JL, Isaacs C. Prevalence of Homologous Recombination-Related Gene Mutations Across Multiple Cancer Types. JCO Precis Oncol. 2018;2018:PO.17.00286. doi: 10.1200/PO.17.00286. Epub 2018 Jul 23.

    PubMed 30234181

Questions about this trial

What is this clinical trial studying?

An observational study of Non-small Cell Lung Cancer (NSCLC), run by Hellenic Cooperative Oncology Group at 20 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Greece, Cyprus. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Elefteria Tsolaki (+30 21 0691 2520, hecogoff@otenet.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prevalence of genomic alterations, TMB levels, and mRNA-based immune subtypes (time frame: Baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07900581, which also lists 41 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.

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