Carcinoma, Non-Small-Cell Lung Clinical Trial
Official title:
Phase II Study of AZD9291 in Patients With Advanced Stage Non-small Cell Lung Cancer Following Prior EGFR TKI Therapy With EGFR and T790M Mutations Detected in Plasma Circulating Tumor DNA (PLASMA)
Circulating tumor DNA (ctDNA) is a highly specific and effective biomarker for the detection
of EGFR mutation status. We hypothesise AZD9291 is efficacious in patients with EGFR
sensitizing mutations and T790M detected in plasma ctDNA.
This is a prospective, open label, multi-centre single arm phase II study assessing the
efficacy and safety of AZD9291 monotherapy in patients with stage IIIB or IV harboring
sensitising EGFR mutation (exon 19 deletions or exon 21 L858R substitution mutations) and
T790M who have progressed following prior treatment with an approved EGFR TKI. Approximately
106 subjects will be enrolled.
All patients must have documented radiological progression on EGFR-TKI treatment and on the
last treatment administered prior to enrolling in the study.
As T790M is the most common mechanism of acquired resistance to EGFR TKI, EGFR TKIs targeting
T790M has been developed.
AZD9291 is an oral, potent, irreversible EGFR-TKI selective for sensitizing (EGFRm) and T790M
resistance mutation with a significant selectivity margin against wild-type EGFR. As a
result, AZD9291 can effectively block EGFR signaling both in EGFR single mutant cells with
activating EGFR mutations and in double mutant cells bearing the resistance T790M mutation.
This is a prospective, open label, multi-centre single arm phase II study assessing the
efficacy and safety of AZD9291 monotherapy in patients with stage IIIB or IV harboring
sensitising EGFR mutation (exon 19 deletions and exon 21 L858R substitution mutations) and
T790M who have progressed following prior treatment with an approved EGFR TKI. Approximately
108 subjects will be enrolled.
All patients must have documented radiological progression on EGFR-TKI treatment and on the
last treatment administered prior to enrolling in the study.
Target patient population:
Patients will be > 18 years of age, with a diagnosis of locally advanced/metastatic NSCLC not
amenable to curative surgery or radiotherapy with documented activating EGFR mutations (exon
19 deletions and exon 21 L858R substitution mutations) at the time of initial diagnosis, have
radiological disease progression following either 1st line EGFR TKI treatment OR following
prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy. Plasma sample must
harbour an EGFR mutation known to be associated with EGFR TKI sensitivity (exon 19 deletion,
L858R as well as presence of T790M by central lab testing from a plasma sample taken after
confirmation of disease progression on the most recent treatment regimen. Patients must have
normal organ and bone marrow function and ECOG PS 0-2.
Treatment and regimens:
Patient will be treated with AZD9291 at a starting dose of 80mg once a day until the patient
completes the study, withdraws from the study or closure of the study. A cycle of treatment
is defined as 28 days of once daily AZD9291 treatment. Patients may continue to receive
AZD9291 until objective disease progression (determined by RECIST 1.1) or if the subject is
no longer receiving clinical benefit in the Investigator's opinion.
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