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Locally Advanced or Metastatic NSCLCNCT03969823

Whole Genomic Landscape of Advanced EGFR-mutant NSCLC

A study testing Tagrisso in people with Locally Advanced or Metastatic NSCLC, run by Seoul National University Hospital at 3 sites in South Korea.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a phase 2 single-arm, non-randomized multicentre and tissue acquisition study to evaluate acquired resistance mechanisms, efficacy, and safety in advanced, EGFR tyrosine kinase inhibitor-naïve NSCLC patients with EGFR-activating mutations who receive a first-line osimertinib orally at a dose of 80mg once daily. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Locally Advanced or Metastatic NSCLC
What is being tested?
Tagrisso
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
148 participants
Where
3 sitesSouth Korea
Study dates
23 May 2019to 31 Dec 2026
Phase
Interventional
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of informed consent prior to any study specific procedures
  • Male or female must be > 19 years of age
  • Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
  • Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
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  • Male subjects should be willing to use barrier contraception (see Restrictions, Section 3.8)
  • Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy with local confirmation of the presence of EGFR TKI-sensitizing mutation (EGFR exon 19 deletion or L858R mutation), either alone or in combination with other EGFR mutations excluding EGFR exon 20 insertion mutation
  • Mandatory provision of fresh tumor sample before osimertinib via a biopsy or surgical resection
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must have a life expectancy ≥ 12 weeks.
  • At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements
  • Provision of informed consent for whole-genome and whole-exome sequencings

Who cannot join

  • Involvement in the planning and/or conduct of the study
  • Previous treatment with an EGFR TKI
  • Patients with different kinds of cancers within 5 years or with malignants simultaneously (except completely cured skin basal cell carcinoma or uterine cervical cancer)
  • Treatment with an investigational drug within five half-lives or 3 months. Patients receiving an radiotherapy targeting brain metastasis or spinal cord compression within 2 weeks before the beginning of study treatment, receiving an wide field radiotherapy over 30% of spinal cord reactivity or who are unrecovered from radiotherapy toxicity
  • Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4
  • Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2, prior platinum-therapy-related neuropathy
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  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required
  • Patients with spinal cord compression, symptomatic or unstable brain metastases except for those patients who have completed definitive therapy and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. Patients who may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are clinically asymptomatic are eligible
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
  • Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values: absolute neutrophil count <1.5 x 109/L; platelet count <100 x 109/L; haemoglobin <90 g/L; alanine aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases; aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases; total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome [unconjugated hyperbilirubinaemia] or liver metastases; serum creatinine >1.5 times ULN concurrent with creatinine clearance <50 mL/min [measured or calculated by Cockcroft and Gault equation]-confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN
  • History of hypersensitivity to any of the active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib
  • Patients who are pregnant or breast-feeding
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
  • Previous allogeneic bone marrow transplant
  • Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection

Trial locations and contacts

3 sites in 1 country.

South Korea3 sites

  • Seoul National University Bundang Hospital

    Seongnam

  • Borame Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

Other trials in South Korea

About this study

Official title: Whole Genomic Landscape of EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Treated With First-Line Osimertinib (WARRIOR)

This is a phase 2 single-arm, non-randomized multicentre and tissue acquisition study to evaluate acquired resistance mechanisms, efficacy, and safety in advanced, EGFR tyrosine kinase inhibitor-naïve NSCLC patients with EGFR-activating mutations who receive a first-line osimertinib orally at a dose of 80mg once daily.

Read the detailed description

This open-label, single-arm, non-randomized phase 2 exploratory study has been designed to evaluate the mechanisms of resistance to first-line osimertinib 80mg once daily in NSCLC patients with EGFR-activating mutation who were naïve to chemotherapy as well as EGFR TKIs. Acquired resistance to first-line osimertinib is mediated by heterogeneous mechanisms including MET amplification (15%), secondary EGFR mutation including C797S or S768I (7%), PIK3CA mutation (7%), CDK4/6 amplification (5%), KRAS mutation (3%), BRAF mutation (3%), CCND1-3 amplification (3%), CCNE1 amplification (2%), HER2 amplification (2%), and SPTBN1-ALK fusion (1%) using plasma genotyping of FLAURA study (N=91). Therefore, this study is necessary to evaluate resistance mechanisms of ≥1% to first-line osimertinib in NSCLC patients with EGFR-activating mutations using whole-genomic profiling of tumours at pre-treatment and progression which acquisitions are mandatory.

Being tested
Tagrisso
Keywords
NSCLC, Osimertinib, EGFR exon 19 deletion or L858R mutation
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.

  • TagrissoDrug

    Also called Osimertinib

    Osimertinib 80mg once daily until disease progression

Study groups in NCT03969823
Study groupRoleWhat they receive
OsimertinibExperimentalOsimertinib at 80mg dose will be administered orally once daily.
Receives: Drug: Tagrisso

What is being measured

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

  1. Proportion of acquired resistance mechanisms to osimertinib at disease progression

    Disease progression as defined by investigator assessments according to RECIST1.1

    Measured: Through study completion, an average of 2 years

Secondary outcomes (4)

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    AEs/SAEs as defined by NCI CTCAE version 5.0

    Measured: Through study completion, an average of 2 years

  2. Progression-Free Survival (PFS)

    PFS as defined as the time from the date of initiation until the date of first documented progression

    Measured: Through study completion, an average of 2 years

  3. Overall Survival (OS)

    OS as defined as the time from the date of first dose until death due to any cause

    Measured: Through study completion, an average of 2 years

  4. Objective Response Rate (ORR)

    ORR using investigator assessments according RECIST1.1

    Measured: Through study completion, an average of 2 years

Timeline

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

  1. First posted31 May 2019
  2. Study start23 May 2019
  3. Primary completion30 Sep 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
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
148 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03969823
Sponsor's protocol ID
ESR-18-14174
Status last verified
Apr 2026
First submitted
28 May 2019
Last updated
24 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Tagrisso in people with Locally Advanced or Metastatic NSCLC, run by Seoul National University Hospital at 3 sites in South Korea.

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

Who may be eligible to take part?

The sponsor lists 13 inclusion and 20 exclusion criteria. 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: under way, not looking for participants, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Korea. 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of acquired resistance mechanisms to osimertinib at disease progression (time frame: Through study completion, an average of 2 years). 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 NCT03969823.

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 24 Apr 2026.

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