This is an open-label, non-randomized, multicenter phase Ib/II study, which is composed of a phase Ib dose escalation part and a phase II dose expansion part. Patients will receive selumetinib in combination with gefitinib 250mg daily. This study will enroll EGFR-mutated NSCLC patients who have developed acquired resistance to EGFR TKI treatment.
Name: selumetinib
Description: The starting dose of selumetinib in combination with the standard dose of gefitinib (250mg QD) on a continuous dosing schedule will be 50mg QD. Total 3 doses of selumetinib will be tested (50mg QD, 50mg BID and 75mg BID).Type: DrugCapsule
Description: Frequency and characteristics of DLTs to the selumetinib and gefitinib combination using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0. (an expected average of 18 weeks) If one patient experiences a DLT in a group of 3 or more evaluable patients, then the cohort will be expanded to include 6 evaluable patients. If only one DLT is observed in the complete cohort of 6 evaluable patients, then dose escalation may occur.
Measure: To determine the MTD and/or RP2D Time: an expected average of 18 weeksDescription: to estimate overall clinical activity of selumetinib combined with gefitinib in EGFR-mutated NSCLC patients who have acquired resistance to EGFR TKIs
Measure: Overall Response Rate (ORR) Time: Patients will be followed up for 2 years(post disease progression)Single Group Assignment
There are 3 SNPs
A tumor harboring an EGFR mutation known to be associated with drug sensitivity (ie, exon 19 deletion , L858R, L861Q, G719X etc.). --- L858R ---
A tumor harboring an EGFR mutation known to be associated with drug sensitivity (ie, exon 19 deletion , L858R, L861Q, G719X etc.). --- L858R --- --- L861Q ---
In the expansion phase, 10 patients with T790M and 10 patients without T790M will be enrolled. --- T790M ---
In the expansion phase, 10 patients with T790M and 10 patients without T790M will be enrolled. --- T790M --- --- T790M ---