The aim of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.
Name: T790M+ Testing
Name: Baseline Visit Blood & Urine Testing
Name: Baseline ECG
Name: Visual Slit-Lamp Testing
Name: AZD9291 Dosing
Name: Plasma AZD9291 testing
Description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and Super-ARMS platform.
Measure: Concordance of T790M mutation plasma testing between Cobas test and Super-ARMS platform Time: Within 1- 28 days after enrollment and before study treatmentDescription: To assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR- TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.
Measure: Progression Free Survival (PFS) using investigator assessments according to RECIST v1.1 Time: From first dose intake to Progression of disease (PD), up to 3 yearsDescription: To evaluate concordance of T790M mutation plasma testing between the Cobas test and digital PCR platform.
Measure: Concordance of T790M mutation plasma testing between Cobas test and digital PCR platform Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate concordance of T790M mutation plasma testing between the Cobas test and NGS platform.
Measure: Concordance of T790M mutation plasma testing between Cobas test and NGS platform Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate the sensitivity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
Measure: Testing sensitivity Time: Within 1- 28 days after enrollment and before study treatmentDescription: To assess the efficacy of AZD9291 monotherapy by assessment of ORR in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.
Measure: Objective Response Rate (ORR) Time: From first dose intake to end of study, up to 3 yearsDescription: To assess the efficacy of AZD9291 monotherapy by assessment of OS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.
Measure: Overall Survival (OS) Time: From first dose intake to end of study, up to 3 yearsDescription: To evaluate the specificity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
Measure: Testing specificity Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate PPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
Measure: Testing positive predictive value (PPV) Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
Measure: Testing negative predictive value (NPV) Time: Within 1- 28 days after enrollment and before study treatmentDescription: To dynamically monitor EGFR mutations by NGS and digital PCR in ctDNA of patients receiving AZD9291 treatment.
Measure: Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point. Time: every 6 weeks during treatment, up to 3 yearsDescription: To explore the mechanisms of acquired resistance in patients who received AZD9291 treatment by NGS testing of tissue and/or blood samples from the collection at PD versus baseline.
Measure: Changes of distribution of resistance related genes at PD compared with baseline. Time: every 6 weeks during treatment, up to 3 yearsDescription: To describe the genomic profile of long-term survivors, especially to find out potential genomic prognosis and/or predictive factors for AZD9291 long-term efficacy as compared to rapid PD patients.
Measure: Key genetic and proteomic markers including, but not limited to, EGFR mutations Time: every 6 weeks during treatment, up to 3 yearsDescription: To evaluate concordance of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing concordance Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate sensitivity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing sensitivity Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate specificity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing specificity Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate PPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing positive predictive value (PPV) Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate NPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.
Measure: Testing negative predictive value (NPV) Time: Within 1- 28 days after enrollment and before study treatmentDescription: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.
Measure: Objective Response Rate (ORR) Time: From first dose intake to end of study, up to 3 yearsDescription: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.
Measure: Progression Free Survival (PFS) Time: From first dose intake to end of study, up to 3 yearsDescription: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.
Measure: Overall Survival (OS) Time: From first dose intake to end of study, up to 3 yearsAllocation: N/A
Single Group Assignment
There are 2 SNPs
To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.. Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.. --- C797S ---
Detect EGFR T790M Mutation in ctDNA of Chinese Advanced/Metastatic NSCLC Patients by Cobas, Super-ARMS, Digital PCR and NGS and Evaluate Clinical Outcomes of T790M Mutation Positive Patients Who Had AZD9291 Monotherapy. --- T790M ---
Detect EGFR T790M Mutation in ctDNA of Chinese Advanced/Metastatic NSCLC Patients by Cobas, Super-ARMS, Digital PCR and NGS and Evaluate Clinical Outcomes of T790M Mutation Positive Patients Who Had AZD9291 Monotherapy. --- T790M --- --- T790M ---
T790M Plasma Testing Methodology Comparison and Clinical Validation The aim of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. --- T790M ---
T790M Plasma Testing Methodology Comparison and Clinical Validation The aim of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. --- T790M --- --- T790M ---
And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS. --- T790M ---
Concordance of T790M mutation plasma testing between Cobas test and Super-ARMS platform. --- T790M ---
To evaluate concordance of T790M mutation plasma testing between the Cobas test and Super-ARMS platform.. Progression Free Survival (PFS) using investigator assessments according to RECIST v1.1. --- T790M ---
To assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR- TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.. Concordance of T790M mutation plasma testing between Cobas test and digital PCR platform. --- T790M ---
To assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR- TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.. Concordance of T790M mutation plasma testing between Cobas test and digital PCR platform. --- T790M --- --- T790M ---
To evaluate concordance of T790M mutation plasma testing between the Cobas test and digital PCR platform.. Concordance of T790M mutation plasma testing between Cobas test and NGS platform. --- T790M ---
To evaluate concordance of T790M mutation plasma testing between the Cobas test and digital PCR platform.. Concordance of T790M mutation plasma testing between Cobas test and NGS platform. --- T790M --- --- T790M ---
To evaluate concordance of T790M mutation plasma testing between the Cobas test and NGS platform.. Testing sensitivity. --- T790M ---
To assess the efficacy of AZD9291 monotherapy by assessment of ORR in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.. Overall Survival (OS). --- T790M ---
To assess the efficacy of AZD9291 monotherapy by assessment of OS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.. Testing specificity. --- T790M ---
To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.. Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.. --- C797S --- --- T790M ---
To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.. Progression Free Survival (PFS). --- T790M ---
To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.. Overall Survival (OS). --- T790M ---
To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.. Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedures. --- T790M ---
Lung Cancer Objective: The primary objective of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. --- T790M ---
And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS. --- T790M ---
Study measures: Data collected will include patient demographics, smoking history, information needed to determine patient eligibility (including medical history, past and current disease characteristics, and tumor EGFR mutations status, T790M and sensitizing mutations status results and type of test performed), AZD9291 exposure, investigator-reported efficacy (including tumor response and disease progression), overall survival (OS), and safety (including serious adverse events [SAEs], adverse events [AEs]). --- T790M ---
Statistical methods: The concordance of T790M resistance mutation testing between the Cobas test and each of other platforms will be calculated. --- T790M ---
The Kappa coefficient will be calculated to measure the agreement of T790M mutation testing between the Cobas test and each of other platforms. --- T790M ---