Osimertinib for Russian EGFR T790M Mutation-positive NSCLC Patients Who Progressed on or After EGFR TKI Therapy

Study Overview
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Brief Summary
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The purpose of this study is to assess safety of Osimertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with progression during or after therapy with a prior EGFR tyrosine kinase inhibitor (TKI), with confirmed Т790М positive mutation in EGFR gene.

Detailed Description
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This study is a multicenter non-interventional retro- and prospective study of safety and efficacy of the Osimertinib administration in frames of Early Access Program (EAP) and real clinical practice in patients with locally advanced or metastatic non-small cell lung cancer that progressed during or after therapy with an EGFR tyrosine kinase inhibitor, with confirmed Т790М positive mutation in EGFR gene with explorative analysis of the set of mutations detected in plasma ctDNA taken after the progression on Osimertinib. It is planned to include in the study approximately 70 patients in the Russian Federation (RF) who are participating or having completed their participation in EAP, or patients, who were treated with Osimertinib in real clinical practice. For the patients participating in EAP and patients taking Osimertinib in real clinical practice, prospective data collection is planned after signing the informed consent form(ICF) for participation in the study. Data from those patients who completed participation in EAP or completed therapy with Osimertinib in real clinical practice will be gathered retrospectively, following the procedure of signing the ICF, or without it, if the procedure is not applicable (patient's death prior to the data collection). Patients who are participating in EAP at the moment of inclusion into the TRUST study will receive therapy by Osimertinib at a dose of 80 mg a day orally, as a single dose. Patients will be treated according to the SmPC and local clinical regulations. Assessment of response to the therapy will be performed in accordance with RECIST 1.1. From all patients included into the study will be performed retro- or prospective data collection of two-year-course of the disease starting from the time of first dose of Osimertinib. For patients with progression of the disease on Osimertinib will be performed molecular-genetic testing of their plasma ctDNA at the time when the fact of the progression is registered. During the study, each patient, for whom data will be collected prospectively, will undergo two data collection points: the first point (for signing of ICF and evaluation of eligibility criteria) and the final point, which will take place 2 years after the first dose of Osimertinib or at the time when therapy by Osimertinib is discontinued. Patients, for whom data will be collected retrospective, should underdo only the first visit for signing the ICF.

Official Title
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Multicenter Non-interventional Study of Osimertinib Administration in Patients With NSCLC Progression Occurred During or After Therapy With EGFR Tyrosine Kinase Inhibitors, With Confirmed Т790М Positive Mutation in EGFR Gene

Conditions
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Non Small Cell Lung Cancer, T790M, EGFR Gene Mutation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in Osimertinib EAP and /or taking / completion therapy with Osimertinib in real clinical practice; Confirmed diagnosis of IIIB (locally advanced) or IV (metastatic) stages of NSCLC with T790M EGFRm; Progression of the disease that occurred during or after the therapy with first- or second-generation EGFR TKI Exclusion Criteria: Participation in any other clinical study; Absence of data essential for obtaining all necessary information in full.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with at least one adverse event | By sex: Male Female By line of treatment: First line therapy Second line of therapy By treatment duration: Up to a year More than a year By effectiveness of therapy: Progression Stabilization Negative feedback Previous targeted therapy: Yes No Variant of mutation: Exon 19 Exon 21 | Through study completion, an average of 5 years | 
| Proportion of patients who discontinued therapy with Osimertinib | By sex: Male Female By line of treatment: First line therapy Second line of therapy By treatment duration: Up to a year More than a year By effectiveness of therapy: Progression Stabilization Negative feedback Previous targeted therapy: Yes No Variant of mutation: Exon 19 Exon 21 | Through study completion, an average of 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate and Objective Response Rate | By sex: Male Female Previous targeted therapy: Yes No Variant of mutation: Exon 19 Exon 21 | Through study completion, an average of 5 years | 
| Progression-free survival | By sex: Male Female Previous targeted therapy: Yes No Variant of mutation: Exon 19 Exon 21 | Through study completion, an average of 5 years | 
| Overall Survival | By sex: Male Female Previous targeted therapy: Yes No Variant of mutation: Exon 19 Exon 21 | Through study completion, an average of 5 years | 
| Time to Treatment Discontinuation | By sex: Male Female Previous targeted therapy: Yes No Variant of mutation: Exon 19 Exon 21 | Through study completion, an average of 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tyrosine kinase inhibitor, Osimertinib