Background: Most pts withEGFR-mut NSCLC progress on EGFR tyrosine kinase inhibitor (TKI) therapy despite high initial response rates. cMET is dysregulated in 15−25% of NSCLC pts with acquired EGFR TKI resistance. INC280 is a highly selective cMET inhibitor with preclinical and preliminary clinical activity in EGFR-mut, cMET+ NSCLC when combined with EGFR TKIs. This Ph Ib/II study evaluates the safety and efficacy of INC280 + gefitinib in pts with EGFR-mut, cMET+ NSCLC who have progressed on gefitinib, erlotinib, or afatinib (NCT01610336). We report here on the Ph II expansion part. Methods: The Ph II primary objective is to estimate the overall clinical activity of INC280 + gefitinib. Secondary objectives include assessing safety and tolerability, and time-dependent clinical activity. Eligible pts ( ≥ 18 years; ECOG PS ≤ 2) must have documented EGFR-mut (exon19del/L858R; no T790M) NSCLC. Pts must have had RECIST-recorded clinical benefit on prior single-agent EGFR TKI before progression, and centrally assessed cMET+ (IHC 3+, or IHC 2+ and gene copy number [GCN] ≥ 5) post-progression. Pts were treated at the RP2D of INC280 400 mg BID (tablet/capsule) + gefitinib 250 mg QD. Results: As of Sep 28 2015, 83 pts were enrolled in the Ph II expansion part (median age 61 years; 84% Asian; 14% PS 0; 55% had 1 prior line of therapy). 66/83 (80%) pts received EGFR TKI as their last single or combined therapy. 42/83 (51%) pts discontinued treatment, mainly due to disease progression (34%). The most common AEs (regardless of causality) were hypoalbuminemia (29%), peripheral edema (27%), and decreased appetite (23%). The most common Grade 3/4 AE (regardless of causality) was increased amylase (7%). Partial responses (PRs) were seen in 12/65 evaluable pts (ORR 18%) and 40/65 (62%) pts had stable disease (SD); disease control rate [PR + SD] 80%. 10/53 pts with IHC 3+ or IHC 2+ and GCN ≥ 5 had PRs (ORR 19%) and 7/23 pts with GCN ≥ 6 had PRs (ORR 30%). Conclusions: INC280 400 mg BID + gefitinib is well-tolerated and shows encouraging clinical activity in EGFR TKI-resistant NSCLC pts, particularly in pts with high cMET GCN. Clinical trial information: NCT01610336