Open Label, Multinational, Multicentre, Real World Treatment Study of Single Agent AZD9291 for Patients With Advanced/Metastatic Epidermal Growth Factor Receptor (EGFR) T790M Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) Who Have Received Prior Therapy With an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI)
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.
- Efficacy of AZD9291 by the analysis of overall survival.
- Safety of AZD9291 by assessment of Serious Adverse Events, Adverse Events of special interest (Interstitial Lung Disease/pneumonitis-like events, Cardiac events)
- Efficacy of AZD9291 by the analysis of Progression Free Survival (PFS)
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, multicentre, real world
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 tumour EGFR mutational status), AZD9291 exposure, investigator-reported
efficacy (including tumour 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%
View this trial on ClinicalTrials.gov