<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/NCT03239340</url>
  </required_header>
  <id_info>
    <org_study_id>D5161C00003</org_study_id>
    <secondary_id>2017-002359-27</secondary_id>
    <nct_id>NCT03239340</nct_id>
  </id_info>
  <brief_title>A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib</brief_title>
  <acronym>ELIOS</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parexel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR&#xD;
      mutation-positive locally advanced or metastatic NSCLC treated with osimertinib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design This is a phase II, open-label, single-arm tissue and plasma acquisition study&#xD;
      assessing the efficacy, safety and underlying resistance mechanisms of osimertinib (80 mg&#xD;
      orally, once daily) as first-line treatment in patients with locally advanced or metastatic&#xD;
      EGFR mutation positive non-small cell lung cancer who are EGFR tyrosine kinase inhibitor&#xD;
      treatment-naïve and eligible for first-line treatment. Participants with EGFR&#xD;
      mutation-positive non-small cell lung cancer will be required to consent to 2 mandatory&#xD;
      tumour biopsies to be considered for enrolment in this study. The first biopsy will be done&#xD;
      prior to initiating treatment with osimertinib and the second biopsy will be obtained any&#xD;
      time between Investigator assessed, Response Evaluation Criteria in Solid Tumours version 1.1&#xD;
      (RECIST 1.1)-defined progression and before the start of any new anticancer treatment. A&#xD;
      third optional biopsy may be taken during the course of treatment at the Investigator's&#xD;
      discretion if the patient consents and if clinically feasible. Tumour tissue and plasma&#xD;
      samples will be collected and examined for genetic and non genetic aberrations that may be&#xD;
      important in determining response and resistance to the treatment that participants will&#xD;
      receive as a part of their cancer care. Patients should continue on osimertinib until&#xD;
      progression or until other treatment discontinuation criteria are met. However, if patients&#xD;
      continue to show clinical benefit to treatment as judged by the Investigator, patients may&#xD;
      continue to receive osimertinib beyond RECIST 1.1-defined progression. Therefore, there is no&#xD;
      maximum duration of treatment. Tumour assessments will be performed at baseline and then&#xD;
      every 8 weeks from study enrolment until 3.5 years, and then every 10 weeks until RECIST&#xD;
      1.1-defined. Patients will be followed up for a period of 28 days following discontinuation&#xD;
      of osimertinib. Target patient population Male and female patients aged 18 years and over&#xD;
      with locally advanced or metastatic pathologically confirmed adenocarcinoma of the lung, not&#xD;
      amenable to curative surgery or radiotherapy. Patients will have a tumour that harbours one&#xD;
      of the EGFR mutations known to be associated with EGFR tyrosine kinase inhibitor sensitivity,&#xD;
      either alone or in combination with other EGFR mutations (EGFR mutation status determined by&#xD;
      a local laboratory). Patients must be EGFR tyrosine kinase inhibitor treatment-naïve and&#xD;
      eligible to receive first line treatment with osimertinib. Osimertinib is an oral, potent,&#xD;
      selective, irreversible inhibitor of both EGFR tyrosine kinase inhibitor sensitizing and&#xD;
      resistance mutations in non-small cell lung cancer with a significant selectivity margin over&#xD;
      wild type EGFR. Osimertinib (80 mg orally, once daily) will be administered. Doses may be&#xD;
      reduced to 40 mg if needed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 30, 2018</start_date>
  <completion_date type="Anticipated">October 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients with a given tumour genetic and proteomic marker at the point of disease progression as defined by the Investigator</measure>
    <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</time_frame>
    <description>To characterize the frequency of genetic and proteomic markers at disease progression regardless of their prevalence.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time toTreatment Discontinuation or Death (TTD)</measure>
    <time_frame>At every visit from enrolment to end of treatment or death or end of study for max 4.2 years</time_frame>
    <description>TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first subsequent therapy or Death (TFST)</measure>
    <time_frame>At every visit from enrolment to start of first subsequent therapy or death or end of study for max 4.2 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate</measure>
    <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</time_frame>
    <description>Percentage of patients who have a best overall response, complete response, partial response or stable disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS in patient subgroups defined by molecular profile</measure>
    <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</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR in patient subgroups defined by molecular profile</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTD in patient subgroups defined by molecular profile</measure>
    <time_frame>At every visit from enrolment to start of first subsequent therapy or death or end of study for max 4.2 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumour shrinkage/depth of response in patient subgroups defined by molecular profile</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with pre-specified characteristics will be summarised by molecular profile</measure>
    <time_frame>At baseline</time_frame>
    <description>The patient characteristics will include: gender (male/female), age (&lt;65yrs/&gt;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.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse events graded by Common Terminology Criteria for Adverse Events version 4.0</measure>
    <time_frame>At every visit from signing informed consent until 28 days after last dose of study treatment</time_frame>
    <description>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</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">154</enrollment>
  <condition>EGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Osimertinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>An oral, potent, selective, irreversible inhibitor of both EGFR-tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Osimertinib</intervention_name>
    <description>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.</description>
    <arm_group_label>Osimertinib</arm_group_label>
    <other_name>TAGRISSO, AZD9291</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of informed consent prior&#xD;
&#xD;
          2. Patients aged 18 years or older&#xD;
&#xD;
          3. Patients with histological confirmation of locally advanced or metastatic NSCLC&#xD;
&#xD;
          4. Patients with M1 stage according to the Tumor, Node and Metastasis Classification of&#xD;
             Malignant Tumours (TNM)&#xD;
&#xD;
          5. Patients with an EGFR deletion or mutation known (from tumour biopsy or plasma) to be&#xD;
             associated with EGFR TKI sensitivity&#xD;
&#xD;
          6. Existence of measurable or evaluable disease (as per RECIST 1.1 criteria).&#xD;
&#xD;
          7. Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection&#xD;
             of the primary tumour or metastatic tumour tissue&#xD;
&#xD;
          8. WHO performance status 0-1&#xD;
&#xD;
          9. Life expectancy ≥12 weeks&#xD;
&#xD;
         10. Capacity to swallow&#xD;
&#xD;
         11. Patients able to complete study and within geographical proximity allowing for&#xD;
             adequate follow up&#xD;
&#xD;
         12. Resolution of all acute toxic effects of previous anticancer therapy&#xD;
&#xD;
         13. Female patients must be using highly effective contraceptive measures, and must have a&#xD;
             negative pregnancy test prior to start of dosing if of childbearing potential&#xD;
&#xD;
         14. Male patients must be willing to use barrier contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Locally advanced lung cancer candidate for curative treatment through radical surgery&#xD;
             and/or radio(chemo)therapy&#xD;
&#xD;
          2. Patients diagnosed with another lung cancer subtype&#xD;
&#xD;
          3. Patients with an EGFR exon 20 insertion&#xD;
&#xD;
          4. Patients with just one measurable or evaluable tumour lesion that has been resected or&#xD;
             irradiated prior to their enrolment in the study&#xD;
&#xD;
          5. Second active neoplasia&#xD;
&#xD;
          6. Treatment with an investigational drug within five half-lives of the compound&#xD;
&#xD;
          7. Participation in another clinical study with an investigational product (IP) during&#xD;
             the last 3 weeks before the first day of study treatment&#xD;
&#xD;
          8. Patients who have received prior immunotherapies&#xD;
&#xD;
          9. Patients who have received prior EGFR treatments for lung cancer&#xD;
&#xD;
         10. Patients who have received prior treatment with an EGFR TKI including in the adjuvant&#xD;
             setting&#xD;
&#xD;
         11. Patients who have received previous treatment for metastatic or stage IV disease&#xD;
&#xD;
         12. Prior treatment with cytotoxic chemotherapy for advanced NSCLC&#xD;
&#xD;
         13. Patients with a history of cancer that has been completely treated, with no evidence&#xD;
             of malignant disease currently cannot be enrolled in the study if their chemotherapy&#xD;
             was completed less than 6 months prior and/or have received a bone marrow transplant&#xD;
             less than 2 years before the first day of study treatment&#xD;
&#xD;
         14. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of&#xD;
             starting study treatment with the exception of alopecia and grade 2, prior&#xD;
             platinum-therapy related neuropathy&#xD;
&#xD;
         15. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled&#xD;
             hypertension and active bleeding diatheses or active infection (eg, patients receiving&#xD;
             treatment for infection) including hepatitis C and human immunodeficiency virus (HIV),&#xD;
             or active uncontrolled Hepatitis B virus (HBV) infection.&#xD;
&#xD;
         16. Patients who have had a surgical procedure unrelated to the study within 14 days or&#xD;
             major surgery within 1 month prior to the administration of the study drug&#xD;
&#xD;
         17. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation&#xD;
             pneumonitis&#xD;
&#xD;
         18. Any of the following cardiac criteria: Mean resting QT interval corrected for heart&#xD;
             rate (QTc) more than 470 msec, obtained from 3 ECGs, using the screening clinic ECG&#xD;
             machine derived QTc value. Any clinically important abnormalities in rhythm,&#xD;
             conduction or morphology of resting ECG e.g. complete left bundle branch block, third&#xD;
             degree heart block and second degree heart block. Any factors that increase the risk&#xD;
             of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia,&#xD;
             hypomagnesaemia, hypocalcaemia, congenital long QT syndrome, family history of long QT&#xD;
             syndrome or unexplained sudden death under 40 years of age in first degree relatives&#xD;
             or any concomitant medication known to prolong the QT interval&#xD;
&#xD;
         19. Spinal cord compression, symptomatic and unstable brain metastases except for those&#xD;
             patients who have completed definitive therapy, and have had a stable neurological&#xD;
             status for at least 2 weeks after completion of definitive therapy. 20.Refractory&#xD;
             nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the&#xD;
             formulated product or previous significant bowel resection that would preclude&#xD;
             adequate absorption of osimertinib&#xD;
&#xD;
        21.Inadequate bone marrow reserve or organ function 22.Female patients who are&#xD;
        breastfeeding 23.Patients currently receiving medications or herbal supplements known to be&#xD;
        potent inducers of cytochrome (CYP) 3A4.&#xD;
&#xD;
        24.Patient unwilling to undergo a biopsy at the time of disease progression 25.History of&#xD;
        hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar&#xD;
        chemical structure or class to osimertinib 26.Judgment by the Investigator that the patient&#xD;
        should not participate in the study if the patient is unlikely to comply with study&#xD;
        procedures, restrictions and requirements 27.Involvement in the planning and/or conduct of&#xD;
        the study 28.Previous enrolment in the present study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zosia Piotrowska, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Athens</city>
        <state>Georgia</state>
        <zip>30607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brescia</city>
        <zip>25100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Meldola</city>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Monza</city>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Parma</city>
        <zip>43126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Roma</city>
        <zip>00152</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Terni</city>
        <zip>05100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Busan</city>
        <zip>47392</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cheongiu</city>
        <zip>28644</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seongnam</city>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Johor Bahru</city>
        <zip>81100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kuantan</city>
        <zip>25100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kuching</city>
        <zip>93586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lembah Pantai</city>
        <zip>59100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pulau Pinang</city>
        <zip>10450</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>A Coruña</city>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Las Palmas de Gran Canaria</city>
        <zip>35016</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Malaysia</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Austria</country>
  </removed_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>June 23, 2023</last_update_submitted>
  <last_update_submitted_qc>June 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EGFR, NSCLC, Lung Cancer, Biopsy, Molecular Profiling</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osimertinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_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.</ipd_time_frame>
    <ipd_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.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03239340
org study id: D5161C00003
secondary id: 2017-002359-27
nct id: NCT03239340
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR
      mutation-positive locally advanced or metastatic NSCLC treated with osimertinib.
Study design This is a phase II, open-label, single-arm tissue and plasma acquisition study
      assessing the efficacy, safety and underlying resistance mechanisms of osimertinib (80 mg
      orally, once daily) as first-line treatment in patients with locally advanced or metastatic
      EGFR mutation positive non-small cell lung cancer who are EGFR tyrosine kinase inhibitor
      treatment-naïve and eligible for first-line treatment. Participants with EGFR
      mutation-positive non-small cell lung cancer will be required to consent to 2 mandatory
      tumour biopsies to be considered for enrolment in this study. The first biopsy will be done
      prior to initiating treatment with osimertinib and the second biopsy will be obtained any
      time between Investigator assessed, Response Evaluation Criteria in Solid Tumours version 1.1
      (RECIST 1.1)-defined progression and before the start of any new anticancer treatment. A
      third optional biopsy may be taken during the course of treatment at the Investigator's
      discretion if the patient consents and if clinically feasible. Tumour tissue and plasma
      samples will be collected and examined for genetic and non genetic aberrations that may be
      important in determining response and resistance to the treatment that participants will
      receive as a part of their cancer care. Patients should continue on osimertinib until
      progression or until other treatment discontinuation criteria are met. However, if patients
      continue to show clinical benefit to treatment as judged by the Investigator, patients may
      continue to receive osimertinib beyond RECIST 1.1-defined progression. Therefore, there is no
      maximum duration of treatment. Tumour assessments will be performed at baseline and then
      every 8 weeks from study enrolment until 3.5 years, and then every 10 weeks until RECIST
      1.1-defined. Patients will be followed up for a period of 28 days following discontinuation
      of osimertinib. Target patient population Male and female patients aged 18 years and over
      with locally advanced or metastatic pathologically confirmed adenocarcinoma of the lung, not
      amenable to curative surgery or radiotherapy. Patients will have a tumour that harbours one
      of the EGFR mutations known to be associated with EGFR tyrosine kinase inhibitor sensitivity,
      either alone or in combination with other EGFR mutations (EGFR mutation status determined by
      a local laboratory). Patients must be EGFR tyrosine kinase inhibitor treatment-naïve and
      eligible to receive first line treatment with 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. Osimertinib (80 mg orally, once daily) will be administered. Doses may be
      reduced to 40 mg if needed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 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
description: To characterize the frequency of genetic and proteomic markers at disease progression regardless of their prevalence.
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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
description: TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.
measure: 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
description: 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.
measure: 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
description: Percentage of patients who have a best overall response, complete response, partial response or stable disease.
measure: 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
description: 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).
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
measure: Proportion of patients with pre-specified characteristics will be summarised by molecular profile
time frame: At baseline
description: 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.
measure: 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
description: 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
arm group label: Osimertinib
arm group type: Experimental
description: An oral, potent, selective, irreversible inhibitor of both EGFR-tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer
intervention type: Drug
intervention name: Osimertinib
description: 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.
arm group label: Osimertinib
other name: TAGRISSO, AZD9291
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
last name: Zosia Piotrowska, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
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country: Italy
country: Korea, Republic of
country: Malaysia
country: Spain
country: United States
country: Austria
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Osimertinib
sharing ipd: Yes
ipd 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.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd 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.
ipd 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.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home