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.
Name: AZD9291
Description: oral administration as a single daily dose of 80 mgType: DrugAZD9291
Single Group Assignment
There are 2 SNPs
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. --- L858R ---
3. Locally advanced/metastatic NSCLC not amenable to curative surgery or radiotherapy 4. Documentation of activating EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) at the time of initial diagnosis 5. Radiological documentation of disease progression: following 1st line EGFR TKI treatment but who have not received further treatment OR following prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy. --- L858R ---
7. Plasma sample must harbour an EGFR mutation known to be associated with EGFR TKI sensitivity (exon 19 deletion, L858R). --- L858R ---
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. --- L858R ---
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. --- L858R ---
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. --- L858R ---
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). --- T790M ---
Phase II Study of AZD9291 in Advanced Stage NSCLC With EGFR and T790M Mutations Detected in Plasma Ct-DNA Circulating tumor DNA (ctDNA) is a highly specific and effective biomarker for the detection of EGFR mutation status. --- T790M ---
We hypothesise AZD9291 is efficacious in patients with EGFR sensitizing mutations and T790M detected in plasma ctDNA. --- T790M ---
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. --- L858R --- --- T790M ---
Confirmation of T790M status by central lab testing from a plasma sample taken after confirmation of disease progression on the most recent treatment regimen. --- T790M ---
Carcinoma, Non-Small-Cell Lung Carcinoma, Non-Small-Cell Lung As T790M is the most common mechanism of acquired resistance to EGFR TKI, EGFR TKIs targeting T790M has been developed. --- T790M ---
Carcinoma, Non-Small-Cell Lung Carcinoma, Non-Small-Cell Lung As T790M is the most common mechanism of acquired resistance to EGFR TKI, EGFR TKIs targeting T790M has been developed. --- T790M --- --- T790M ---
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. --- T790M ---
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. --- T790M ---
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. --- L858R --- --- T790M ---
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. --- L858R --- --- T790M ---