Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation NSCLC
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real
      world setting in adult patients with advanced or metastatic, epidermal growth factor receptor
      (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior
      EGFR-tyrosine kinase inhibitor (TKI) therapy.
    

Detailed description: 
      Objective: The primary objective of this study is to assess the efficacy and safety of single
      agent AZD9291 in a real world setting in adult patients with advanced or metastatic,
      epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer
      (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.

      Study site(s) and number of patients planned: Approximately 1500 patients will be recruited
      in Europe. The recruitment will be increased beyond that as the study will expand in other
      regions of the world (America, Asia).

      Study Design This will be an open-label, single-arm, multinational, multicenter, real world
      treatment study.

      Target patient population: Adult patients (fulfilling the definition of "age of majority" per
      local regulations) with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC with
      confirmed T790M mutation, who have received prior EGFR-TKI therapy.

      Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent,
      selective, irreversible inhibitor of both EGFR-TKI sensitising 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 each participating country as soon as
      possible following national reimbursement of AZD9291 in that country (up to a max of 90 days
      post reimbursement). Enrolment will be closed within 6 months after market license approval
      in that country or at national reimbursement, whichever is sooner. Patients withdrawing from
      the treatment prior to national reimbursement will be followed up as part of this study.
      Patients on treatment will receive commercial supply until documented disease progression as
      per investigator assessment.

      In the event that national reimbursement should not be granted following a reasonable time
      after market license approval in the country, the study will be closed in a maximum period of
      18 months after the last patient is enrolled in that country. If applicable, timelines for
      conversion to commercial drug will be agreed with local bodies which may include regulatory
      agencies, ethics committees, and institutions. Patient will be followed until death or lost
      to follow-up.

      Study measures: Data collected will include patient demographics, information needed to
      determine patient eligibility (including medical history, past and current disease
      characteristics, and tumor EGFR mutational status), AZD9291 exposure, investigator-reported
      efficacy (including tumor response and disease progression), overall survival (OS), and
      safety (including serious adverse events [SAEs], adverse events leading to dose modification,
      and adverse events of special interest [interstitial lung disease/pneumonitis-like events,
      and QTc prolongation events]).

      Statistical methods: All data will be presented for the overall full analysis/evaluable set,
      and also by cohorts defined by number and type of previous treatment lines for the advanced
      disease. Descriptive statistics will be used for all variables, as appropriate. Continuous
      variables will be summarised by the number of observations, mean, standard deviation, median,
      minimum, and maximum. Categorical variables will be summarised by frequency counts and
      percentages for each category. OS and PFS will be summarized using Kaplan-Meier estimates of
      the median time to death or censoring and quartiles together with their 95% confidence
      intervals.
    

Intervention name(s): T790M+ Testing; Baseline Visit Blood & Urine Testing; Baseline ECG; Visual Slit-Lamp Testing; AZD9291 Dosing
Intervention type(s): Procedure; Procedure; Procedure; Procedure; Drug
Intervention description(s): If a previous lab report is unavailable, the patient will need to have T790M+ testing.; Blood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria; ECG to ensure absence of any cardiac abnormality; Slit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms; Patients to be provided with AZD9291 every 6 weeks (+/- 7 days)
Intervention MeSH terms: Osimertinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: NSCLC; EGFRm; T790M