The primary goal is to evaluate the efficacy of osimertinib (AZD9291), in terms of the objective response rate in patients with advanced non-squamous NSCLC with EGFR mutations and the EGFR T790M mutation at diagnosis as defined by RECIST 1.1 criteria. Safety and efficacy will also be measured.
Name: Osimertinib
Description: Defined as the rate of complete responses [CR] or partial responses [PR] to treatment in accordance to the guidelines of RECIST version 1.1 criteria
Measure: Objective response rate Time: Baseline up to 78 weeks after patient entryDescription: Patient safety and adverse events will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) of the U.S. National Cancer Institute (NCI), version 4
Measure: Grade 3 or 4 adverse events and SAEs Time: Baseline up to 78 weeks after patient entryDescription: Time from treatment start to the time of death due to any cause
Measure: Overall survival Time: Baseline up to 78 weeks after patient entryDescription: Time from treatment start to the time at which the patient discontinues treatment due to any cause
Measure: Time to treatment failure Time: Baseline up to 78 weeks after patient entryDescription: Time from the first documented response to documented disease progression or death
Measure: Duration of response Time: Baseline up to 78 weeks after patient entryDescription: Percentage of patients with complete response, partial response or stable disease for a minimum of 24 weeks, assessed in accordance with the modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, during all study period from baseline up to 78 weeks after patient entry
Measure: Disease control rate Time: Baseline up to 78 weeks after patient entryDescription: Correlation ratio of mutational status and documented clinical response
Measure: Correlation ratio between mutational status and clinical response Time: Baseline up to 78 weeks after patient entryDescription: Measured by Percentage of patients with a positive EGFR mutation in plasma
Measure: Overall plasma EGFR mutation status Time: Baseline up to 78 weeks after patient entryDescription: Percentage of patients who develop anti-drug mutations in tumour tissue
Measure: Acquired resistance to osimertinib (AZD9291) by histology Time: Baseline up to 78 weeks after patient entryDescription: Percentage of patients who develop anti-drug mutations in plasma
Measure: Overall plasma acquired resistance to osimertinib (AZD9291) Time: Baseline up to 78 weeks after patient entryAllocation: N/A
Single Group Assignment
There are 3 SNPs
- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally. --- L858R ---
- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment that have not been confirmed centrally. --- L858R ---
- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally. --- L858R --- --- L861Q ---
- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment that have not been confirmed centrally. --- L858R --- --- L861Q ---
A Phase IIa Clinical Trial to Evaluate the Safety and Efficacy of Osimertinib (AZD9291) in First-line Patients With EGFR Mutation-positive Locally Advanced or Metastatic Non-small Cell Lung Cancer and Concomitant EGFR T790M Mutation at Time of Diagnosis. --- T790M ---
Osimertinib (AZD9291) in First-line Locally Advanced or Metastatic NSCLC Patients With EGFR and EGFR T790M The primary goal is to evaluate the efficacy of osimertinib (AZD9291), in terms of the objective response rate in patients with advanced non-squamous NSCLC with EGFR mutations and the EGFR T790M mutation at diagnosis as defined by RECIST 1.1 criteria. --- T790M ---
Osimertinib (AZD9291) in First-line Locally Advanced or Metastatic NSCLC Patients With EGFR and EGFR T790M The primary goal is to evaluate the efficacy of osimertinib (AZD9291), in terms of the objective response rate in patients with advanced non-squamous NSCLC with EGFR mutations and the EGFR T790M mutation at diagnosis as defined by RECIST 1.1 criteria. --- T790M --- --- T790M ---
Inclusion Criteria: - Patient aged 18 years or older - Patients with histological confirmation of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with an activating EGFR mutation and concomitant T790M mutation who are not candidates for local curative treatment. --- T790M ---
- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally. --- L858R --- --- L861Q --- --- T790M ---
- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment that have not been confirmed centrally. --- L858R --- --- L861Q --- --- T790M ---
Non-Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung Naïve patients ≥ 18 years of age with histological confirmation of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with an activating EGFR mutation and concomitant T790M mutation. --- T790M ---
Primary objective: - To evaluate the efficacy of osimertinib (AZD9291), in terms of the objective response rate in patients with advanced non-squamous NSCLC with EGFR mutations and the EGFR T790M mutation at diagnosis as defined by RECIST 1.1 criteria. --- T790M ---
- To carry out a longitudinal analysis of EGFR mutations (including the T790M mutation) in plasma and serum. --- T790M ---