A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib
Condition: EGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR
      mutation-positive locally advanced or metastatic NSCLC treated with osimertinib.
    

Detailed description: 
      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.
    

Intervention name(s): Osimertinib
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): TAGRISSO, AZD9291
Intervention MeSH terms: Osimertinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: EGFR, NSCLC, Lung Cancer, Biopsy, Molecular Profiling