Bi 1482694 (Hm61713), An Egfr Mutant-Specific Inhibitor, In T790m+Nsclc: Efficacy And Safety At The Rp2d.

9055 Background: T790M mediates acquired resistance to 1st/2nd generation EGFR-TKIs. BI 1482694 is a 3rd generation TKI active against mutant EGFR, including T790M. This Phase I/II trial is evaluating BI 1482694 in Korean patients (pts) with EGFR-TKI pre-treated NSCLC (NCT01588145). Preliminary data in T790M+ pts treated at the RP2D (800 mg/d) were reported previously (Lee et al. ESMO Asia 2015); as of 30 Jun 2015, ORR by independent review was 62% (confirmed ORR 46%). Here we present updated efficacy and safety findings as of 30 Nov 2015. Methods: Pts with locally advanced or metastatic EGFR mutant NSCLC who previously received an EGFR-TKI and had centrally confirmed T790M+ tumors were recruited in Phase II. Pts received BI 1482694 800 mg/d until disease progression, unacceptable toxicity, or other stopping criteria. Tumors were assessed every 6 wks by investigator and independent review. Pts were evaluable for response if they had at least one tumor assessment post baseline; PFS and safety were evaluated in all treated pts. Results: Among 76 T790M+ pts who received BI 1482694 800 mg in Phase II, median age was 60 yrs, 58% were female, 80% had ECOG PS ≤ 1, and 75% had ≥ 2 prior lines of systemic therapy, including EGFR-TKI. Median treatment duration was 7.0 mos (range 0.3–13.8); 26 (34%) pts remain on treatment at data cut-off. Most common drug-related (DR) AEs (all/grade ≥ 3) were diarrhea (55%/0), rash (39%/5%), pruritus (39%/1%), and nausea (38%/0). 3 (4%) pts discontinued due to DR AEs (abdominal pain upper and vomiting [n = 1], interstitial lung disease [n = 1], neuropathy peripheral [n = 1]). 9 (12%) pts had serious DR AEs. There were no AEs of QT prolongation or hyperglycemia and no DR deaths. Of 71 pts evaluable for response, 40 (56%) had an objective response by investigator review (31 [44%] confirmed) with median duration of response 8.3 mos (range 5.6–NE). Disease control rate was 90%. Median PFS by investigator review was 7.0 mos (95% CI 5.5–8.3). Updated efficacy data by independent review will be presented at the meeting. Conclusions: BI 1482694 showed meaningful clinical activity with favorable tolerability in Korean pts with EGFR-TKI-resistant T790M+ NSCLC, and is being further evaluated in the global Phase II ELUXA 1 trial. Clinical trial information: NCT01588145.