<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02997501</url>
  </required_header>
  <id_info>
    <org_study_id>D5160C00042</org_study_id>
    <nct_id>NCT02997501</nct_id>
  </id_info>
  <brief_title>T790M Plasma Testing Methodology Comparison and Clinical Validation</brief_title>
  <acronym>ADELOS</acronym>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>TigerMed</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to evaluate concordance of T790M mutation plasma testing between the&#xD;
      Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. And to assess the&#xD;
      efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or&#xD;
      metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and&#xD;
      are T790M mutation positive detected by any one of the four plasma testing platforms:&#xD;
      Cobas/Super-ARMS/ digital PCR/NGS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective: The primary objective of this study is to evaluate concordance of T790M mutation&#xD;
      plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or&#xD;
      NGS. And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients&#xD;
      with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor&#xD;
      (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing&#xD;
      platforms: Cobas/Super-ARMS/ digital PCR/NGS.&#xD;
&#xD;
      Study number of patients planned: Approximately 250 patients will be recruited in China.&#xD;
&#xD;
      Study Design: This is an open-label, multi-center testing and treatment study.&#xD;
&#xD;
      Target patient population: 250 locally advanced or metastatic EGFR mutation positive NSCLC&#xD;
      patients with progression on a previous EGFR-TKI will be recruited.&#xD;
&#xD;
      Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent,&#xD;
      selective, irreversible inhibitor of both EGFR-TKI sensitizing and resistance mutations in&#xD;
      NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will be administered&#xD;
      orally as one 80 mg tablet once a day.&#xD;
&#xD;
      Duration of IP administration: Patients may continue to receive AZD9291 as long as they&#xD;
      continue to show clinical benefit, as judged by the investigator, and in the absence of&#xD;
      discontinuation criteria. The study will be closed in a maximum period of 18 months after the&#xD;
      last patient is enrolled. Contingencies will be made to ensure continued drug supply for&#xD;
      patients who are still deriving benefit from AZD9291 at that time.&#xD;
&#xD;
      Study measures: Data collected will include patient demographics, smoking history,&#xD;
      information needed to determine patient eligibility (including medical history, past and&#xD;
      current disease characteristics, and tumor EGFR mutations status, T790M and sensitizing&#xD;
      mutations status results and type of test performed), AZD9291 exposure, investigator-reported&#xD;
      efficacy (including tumor response and disease progression), overall survival (OS), and&#xD;
      safety (including serious adverse events [SAEs], adverse events [AEs]).&#xD;
&#xD;
      Statistical methods: The concordance of T790M resistance mutation testing between the Cobas&#xD;
      test and each of other platforms will be calculated. The sensitivity, specificity, PPV and&#xD;
      NPV of each testing platform (Super-ARMS, digital PCR, and NGS) will be calculated with the&#xD;
      Cobas test as the reference. The Kappa coefficient will be calculated to measure the&#xD;
      agreement of T790M mutation testing between the Cobas test and each of other platforms.&#xD;
      Descriptive statistics will be provided for all variables, as appropriate. Continuous&#xD;
      variables will be summarized by the number of observations, mean, standard deviation, median,&#xD;
      interquartile range (Q1, Q3), minimum, and maximum. Categorical variables will be summarized&#xD;
      by frequency counts and percentages for each category. The 95% confidence interval (CI) will&#xD;
      be calculated as appropriate. PFS and OS, respectively, will be summarized using Kaplan-Meier&#xD;
      estimates of the median time to event (progression and death) and quartiles together with&#xD;
      their 95% confidence intervals.The chi-square test will be used to compare the sensitivity,&#xD;
      specificity, and concordance between any of the two platforms using Cobas as reference&#xD;
      testing in an exploratory manner.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 23, 2016</start_date>
  <completion_date type="Actual">October 24, 2018</completion_date>
  <primary_completion_date type="Actual">October 24, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Concordance of T790M mutation plasma testing between Cobas test and Super-ARMS platform</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate concordance of T790M mutation plasma testing between the Cobas test and Super-ARMS platform.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival (PFS) using investigator assessments according to RECIST v1.1</measure>
    <time_frame>From first dose intake to Progression of disease (PD), up to 3 years</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Concordance of T790M mutation plasma testing between Cobas test and digital PCR platform</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate concordance of T790M mutation plasma testing between the Cobas test and digital PCR platform.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Concordance of T790M mutation plasma testing between Cobas test and NGS platform</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate concordance of T790M mutation plasma testing between the Cobas test and NGS platform.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Testing sensitivity</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate the sensitivity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>From first dose intake to end of study, up to 3 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From first dose intake to end of study, up to 3 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Testing specificity</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate the specificity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Testing positive predictive value (PPV)</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate PPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Testing negative predictive value (NPV)</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.</measure>
    <time_frame>every 6 weeks during treatment, up to 3 years</time_frame>
    <description>To dynamically monitor EGFR mutations by NGS and digital PCR in ctDNA of patients receiving AZD9291 treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes of distribution of resistance related genes at PD compared with baseline.</measure>
    <time_frame>every 6 weeks during treatment, up to 3 years</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Key genetic and proteomic markers including, but not limited to, EGFR mutations</measure>
    <time_frame>every 6 weeks during treatment, up to 3 years</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Testing concordance</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate concordance of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.</description>
  </other_outcome>
  <other_outcome>
    <measure>Testing sensitivity</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate sensitivity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.</description>
  </other_outcome>
  <other_outcome>
    <measure>Testing specificity</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate specificity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.</description>
  </other_outcome>
  <other_outcome>
    <measure>Testing positive predictive value (PPV)</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate PPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.</description>
  </other_outcome>
  <other_outcome>
    <measure>Testing negative predictive value (NPV)</measure>
    <time_frame>Within 1- 28 days after enrollment and before study treatment</time_frame>
    <description>To evaluate NPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.</description>
  </other_outcome>
  <other_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>From first dose intake to end of study, up to 3 years</time_frame>
    <description>To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.</description>
  </other_outcome>
  <other_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>From first dose intake to end of study, up to 3 years</time_frame>
    <description>To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From first dose intake to end of study, up to 3 years</time_frame>
    <description>To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">167</enrollment>
  <condition>Lung Cancer</condition>
  <arm_group>
    <arm_group_label>AZD9291</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single arm of AZD9291, starting dose of 80mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>T790M+ Testing</intervention_name>
    <description>The patient will need to have T790M+ testing</description>
    <arm_group_label>AZD9291</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Baseline Visit Blood &amp; Urine Testing</intervention_name>
    <description>Blood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria</description>
    <arm_group_label>AZD9291</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Baseline ECG</intervention_name>
    <description>ECG to ensure absence of any cardiac abnormality</description>
    <arm_group_label>AZD9291</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Visual Slit-Lamp Testing</intervention_name>
    <description>Slit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms</description>
    <arm_group_label>AZD9291</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD9291 Dosing</intervention_name>
    <description>Patients to be provided with AZD9291 every 6 weeks (+/- 7 days)</description>
    <arm_group_label>AZD9291</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Plasma AZD9291 testing</intervention_name>
    <description>The patient will need to have plasma AZD9291 testing before treatment</description>
    <arm_group_label>AZD9291</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures.&#xD;
&#xD;
          2. Adults (according to China regulations for age of majority)&#xD;
&#xD;
          3. Histological or cytological confirmed locally advanced NSCLC (stage IIIB) or&#xD;
             metastatic (stage IV) NSCLC, not amenable to curative surgery or radiotherapy.&#xD;
&#xD;
          4. Patients who have progressed following prior therapy with an EGFR-TKI agent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who disagree to participate this study.&#xD;
&#xD;
          2. Patients whose medical objection was recorded to use the existing data from medical&#xD;
             practice for scientific research.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yilong WU</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guangdong General Hospita</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Zhiyong LIANG</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Changchun</city>
        <zip>130012</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chengdu</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Guangzhou</city>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wuhan</city>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wuhan</city>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wuhan</city>
        <zip>430079</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Xi'an</city>
        <zip>710038</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <disposition_first_submitted>September 18, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>September 18, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 3, 2019</disposition_first_posted>
  <last_update_submitted>September 18, 2019</last_update_submitted>
  <last_update_submitted_qc>September 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osimertinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 11, 2023</submitted>
    <returned>July 28, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02997501
org study id: D5160C00042
nct id: NCT02997501
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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. 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.

      Study number of patients planned: Approximately 250 patients will be recruited in China.

      Study Design: This is an open-label, multi-center testing and treatment study.

      Target patient population: 250 locally advanced or metastatic EGFR mutation positive NSCLC
      patients with progression on a previous EGFR-TKI will be recruited.

      Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent,
      selective, irreversible inhibitor of both EGFR-TKI sensitizing and resistance mutations in
      NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will be administered
      orally as one 80 mg tablet once a day.

      Duration of IP administration: Patients may continue to receive AZD9291 as long as they
      continue to show clinical benefit, as judged by the investigator, and in the absence of
      discontinuation criteria. The study will be closed in a maximum period of 18 months after the
      last patient is enrolled. Contingencies will be made to ensure continued drug supply for
      patients who are still deriving benefit from AZD9291 at that time.

      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]).

      Statistical methods: The concordance of T790M resistance mutation testing between the Cobas
      test and each of other platforms will be calculated. The sensitivity, specificity, PPV and
      NPV of each testing platform (Super-ARMS, digital PCR, and NGS) will be calculated with the
      Cobas test as the reference. The Kappa coefficient will be calculated to measure the
      agreement of T790M mutation testing between the Cobas test and each of other platforms.
      Descriptive statistics will be provided for all variables, as appropriate. Continuous
      variables will be summarized by the number of observations, mean, standard deviation, median,
      interquartile range (Q1, Q3), minimum, and maximum. Categorical variables will be summarized
      by frequency counts and percentages for each category. The 95% confidence interval (CI) will
      be calculated as appropriate. PFS and OS, respectively, will be summarized using Kaplan-Meier
      estimates of the median time to event (progression and death) and quartiles together with
      their 95% confidence intervals.The chi-square test will be used to compare the sensitivity,
      specificity, and concordance between any of the two platforms using Cobas as reference
      testing in an exploratory manner.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Concordance of T790M mutation plasma testing between Cobas test and Super-ARMS platform
time frame: Within 1- 28 days after enrollment and before study treatment
description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and Super-ARMS platform.
measure: Progression Free Survival (PFS) using investigator assessments according to RECIST v1.1
time frame: From first dose intake to Progression of disease (PD), up to 3 years
description: 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: Concordance of T790M mutation plasma testing between Cobas test and digital PCR platform
time frame: Within 1- 28 days after enrollment and before study treatment
description: 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 NGS platform
time frame: Within 1- 28 days after enrollment and before study treatment
description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and NGS platform.
measure: Testing sensitivity
time frame: Within 1- 28 days after enrollment and before study treatment
description: To evaluate the sensitivity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
measure: Objective Response Rate (ORR)
time frame: From first dose intake to end of study, up to 3 years
description: 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: Overall Survival (OS)
time frame: From first dose intake to end of study, up to 3 years
description: 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: Testing specificity
time frame: Within 1- 28 days after enrollment and before study treatment
description: To evaluate the specificity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
measure: Testing positive predictive value (PPV)
time frame: Within 1- 28 days after enrollment and before study treatment
description: To evaluate PPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
measure: Testing negative predictive value (NPV)
time frame: Within 1- 28 days after enrollment and before study treatment
description: To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.
measure: Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.
time frame: every 6 weeks during treatment, up to 3 years
description: To dynamically monitor EGFR mutations by NGS and digital PCR in ctDNA of patients receiving AZD9291 treatment.
measure: Changes of distribution of resistance related genes at PD compared with baseline.
time frame: every 6 weeks during treatment, up to 3 years
description: 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: Key genetic and proteomic markers including, but not limited to, EGFR mutations
time frame: every 6 weeks during treatment, up to 3 years
description: 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: Testing concordance
time frame: Within 1- 28 days after enrollment and before study treatment
description: 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 sensitivity
time frame: Within 1- 28 days after enrollment and before study treatment
description: 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 specificity
time frame: Within 1- 28 days after enrollment and before study treatment
description: 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 positive predictive value (PPV)
time frame: Within 1- 28 days after enrollment and before study treatment
description: 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 negative predictive value (NPV)
time frame: Within 1- 28 days after enrollment and before study treatment
description: 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: Objective Response Rate (ORR)
time frame: From first dose intake to end of study, up to 3 years
description: 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 frame: From first dose intake to end of study, up to 3 years
description: 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 frame: From first dose intake to end of study, up to 3 years
description: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.
arm group label: AZD9291
arm group type: Experimental
description: Single arm of AZD9291, starting dose of 80mg
intervention type: Procedure
intervention name: T790M+ Testing
description: The patient will need to have T790M+ testing
arm group label: AZD9291
intervention type: Procedure
intervention name: Baseline Visit Blood & Urine Testing
description: Blood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria
arm group label: AZD9291
intervention type: Procedure
intervention name: Baseline ECG
description: ECG to ensure absence of any cardiac abnormality
arm group label: AZD9291
intervention type: Procedure
intervention name: Visual Slit-Lamp Testing
description: Slit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms
arm group label: AZD9291
intervention type: Drug
intervention name: AZD9291 Dosing
description: Patients to be provided with AZD9291 every 6 weeks (+/- 7 days)
arm group label: AZD9291
intervention type: Procedure
intervention name: Plasma AZD9291 testing
description: The patient will need to have plasma AZD9291 testing before treatment
arm group label: AZD9291
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yilong WU
role: Principal Investigator
affiliation: Guangdong General Hospita
last name: Zhiyong LIANG
role: Principal Investigator
affiliation: Peking Union Medical College Hospital
facility: 
facility: 
facility: 
facility: 
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country: China
responsible party type: Sponsor
mesh term: Osimertinib
sharing ipd: Undecided
submitted: July 11, 2023
returned: July 28, 2023