A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib (ELIOS)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03239340 |
Recruitment Status :
Active, not recruiting
First Posted : August 4, 2017
Last Update Posted : December 21, 2022
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Condition or disease | Intervention/treatment | Phase |
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EGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer | Drug: Osimertinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 154 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Multicentre, Open-label, Single-arm, Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib |
Actual Study Start Date : | May 30, 2018 |
Estimated Primary Completion Date : | October 31, 2024 |
Estimated Study Completion Date : | October 31, 2024 |

Arm | Intervention/treatment |
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Experimental: Osimertinib
An oral, potent, selective, irreversible inhibitor of both EGFR-tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer
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Drug: Osimertinib
Osimertinib is an oral, potent, selective, irreversible inhibitor of both EGFR-tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer with a significant selectivity margin over wild type EGFR.
Other Name: TAGRISSO, AZD9291 |
- Proportion of patients with a given tumour genetic and proteomic marker at the point of disease progression as defined by the Investigator [ Time Frame: Tumour Genetic and Proteomic markers will be assessed from tissue samples collected prior to initiation of treatment and at the time of disease progression for max 4.2 years ]To characterize the frequency of genetic and proteomic markers at disease progression regardless of their prevalence.
- Progression-free survival (PFS) [ Time Frame: At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years ]PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed RECIST 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression.
- Objective Response Rate (ORR) [ Time Frame: At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years ]ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later.
- Duration of Response (DoR) [ Time Frame: From time of first documented response until date of documented progression or death in the absence of disease progression or end of study up to max 4.2 years ]DoR is defined as the time from the date of first documented response, (that is subsequently confirmed) until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint.
- Time toTreatment Discontinuation or Death (TTD) [ Time Frame: At every visit from enrolment to end of treatment or death or end of study for max 4.2 years ]TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.
- Time to first subsequent therapy or Death (TFST) [ Time Frame: At every visit from enrolment to start of first subsequent therapy or death or end of study for max 4.2 years ]TFST is defined as the time from the date of first dose of osimertinib to the earlier of the date of anticancer therapy start date following study treatment discontinuation, or death.
- Disease Control Rate [ Time Frame: At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years ]Percentage of patients who have a best overall response, complete response, partial response or stable disease.
- PFS in patient subgroups defined by molecular profile [ Time Frame: At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years ]PFS will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Epidermal growth factor receptor (EGFR) Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived circulating tumour deoxyribonucleic acid (ctDNA).
- ORR in patient subgroups defined by molecular profile [ Time Frame: At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years ]ORR will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.
- TTD in patient subgroups defined by molecular profile [ Time Frame: At every visit from enrolment to start of first subsequent therapy or death or end of study for max 4.2 years ]TTD will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.
- Tumour shrinkage/depth of response in patient subgroups defined by molecular profile [ Time Frame: At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years ]Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions. Tumour shrinkage/depth of response will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.
- Proportion of patients with pre-specified characteristics will be summarised by molecular profile [ Time Frame: At baseline ]The patient characteristics will include: gender (male/female), age (<65yrs/>65yrs), race (Asian/non Asian), and WHO Performance Status (0/1). These will be summarized by subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.
- Adverse events graded by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: At every visit from signing informed consent until 28 days after last dose of study treatment ]To summarize the safety and tolerability profile of osimertinib as first-line EGFR tyrosine kinase inhibitor therapy for patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer

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Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Provision of informed consent prior
- Patients aged 18 years or older
- Patients with histological confirmation of locally advanced or metastatic NSCLC
- Patients with M1 stage according to the Tumor, Node and Metastasis Classification of Malignant Tumours (TNM)
- Patients with an EGFR deletion or mutation known (from tumour biopsy or plasma) to be associated with EGFR TKI sensitivity
- Existence of measurable or evaluable disease (as per RECIST 1.1 criteria).
- Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumour or metastatic tumour tissue
- WHO performance status 0-1
- Life expectancy ≥12 weeks
- Capacity to swallow
- Patients able to complete study and within geographical proximity allowing for adequate follow up
- Resolution of all acute toxic effects of previous anticancer therapy
- Female patients must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential
- Male patients must be willing to use barrier contraception
Exclusion Criteria:
- Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy
- Patients diagnosed with another lung cancer subtype
- Patients with an EGFR exon 20 insertion
- Patients with just one measurable or evaluable tumour lesion that has been resected or irradiated prior to their enrolment in the study
- Second active neoplasia
- Treatment with an investigational drug within five half-lives of the compound
- Participation in another clinical study with an investigational product (IP) during the last 3 weeks before the first day of study treatment
- Patients who have received prior immunotherapies
- Patients who have received prior EGFR treatments for lung cancer
- Patients who have received prior treatment with an EGFR TKI including in the adjuvant setting
- Patients who have received previous treatment for metastatic or stage IV disease
- Prior treatment with cytotoxic chemotherapy for advanced NSCLC
- Patients with a history of cancer that has been completely treated, with no evidence of malignant disease currently cannot be enrolled in the study if their chemotherapy was completed less than 6 months prior and/or have received a bone marrow transplant less than 2 years before the first day of study treatment
- 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
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses or active infection (eg, patients receiving treatment for infection) including hepatitis C and human immunodeficiency virus (HIV), or active uncontrolled Hepatitis B virus (HBV) infection.
- Patients who have had a surgical procedure unrelated to the study within 14 days or major surgery within 1 month prior to the administration of the study drug
- Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis
- Any of the following cardiac criteria: Mean resting QT interval corrected for heart rate (QTc) more than 470 msec, obtained from 3 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, hypomagnesaemia, hypocalcaemia, 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
- Spinal cord compression, symptomatic and 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. 20.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
21.Inadequate bone marrow reserve or organ function 22.Female patients who are breastfeeding 23.Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome (CYP) 3A4.
24.Patient unwilling to undergo a biopsy at the time of disease progression 25.History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib 26.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 27.Involvement in the planning and/or conduct of the study 28.Previous enrolment in the present study

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03239340
United States, Georgia | |
Research Site | |
Athens, Georgia, United States, 30607 | |
Research Site | |
Atlanta, Georgia, United States, 30307 | |
United States, Massachusetts | |
Research Site | |
Boston, Massachusetts, United States, 02215 | |
Italy | |
Research Site | |
Brescia, Italy, 25100 | |
Research Site | |
Meldola, Italy, 47014 | |
Research Site | |
Monza, Italy, 20900 | |
Research Site | |
Parma, Italy, 43126 | |
Research Site | |
Roma, Italy, 00152 | |
Research Site | |
Terni, Italy, 05100 | |
Korea, Republic of | |
Research Site | |
Busan, Korea, Republic of, 47392 | |
Research Site | |
Cheongiu, Korea, Republic of, 28644 | |
Research Site | |
Seongnam, Korea, Republic of, 13620 | |
Research Site | |
Seoul, Korea, Republic of, 03722 | |
Research Site | |
Seoul, Korea, Republic of, 05505 | |
Research Site | |
Seoul, Korea, Republic of, 06591 | |
Research Site | |
Seoul, Korea, Republic of, 135-710 | |
Malaysia | |
Research Site | |
Johor Bahru, Malaysia, 81100 | |
Research Site | |
Kuantan, Malaysia, 25100 | |
Research Site | |
Kuching, Malaysia, 93586 | |
Research Site | |
Lembah Pantai, Malaysia, 59100 | |
Research Site | |
Pulau Pinang, Malaysia, 10450 | |
Spain | |
Research Site | |
A Coruña, Spain, 15006 | |
Research Site | |
Barcelona, Spain, 08035 | |
Research Site | |
Las Palmas de Gran Canaria, Spain, 35016 | |
Research Site | |
Madrid, Spain, 28046 | |
Research Site | |
Sevilla, Spain, 41009 |
Principal Investigator: | Zosia Piotrowska, MD | Massachusetts General Hospital |
Responsible Party: | AstraZeneca |
ClinicalTrials.gov Identifier: | NCT03239340 |
Other Study ID Numbers: |
D5161C00003 |
First Posted: | August 4, 2017 Key Record Dates |
Last Update Posted: | December 21, 2022 |
Last Verified: | December 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
Access Criteria: | When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
EGFR, NSCLC, Lung Cancer, Biopsy, Molecular Profiling |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Osimertinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |