2111 - Phase II results for single-agent nazartinib (EGF816) in adult patients (pts) with treatment-naive EGFR-mutant non-small cell lung cancer (NSCLC)

Background

Nazartinib (EGF816) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that selectively targets activating (L858R, ex19del) and resistance (T790M) mutants, while sparing wild type. In this phase I/II multicenter study in advanced EGFR-mutant NSCLC (NCT02108964), the recommended phase II dose was 150 mg once daily (QD). Phase II primary efficacy and safety data are presented.

Methods

Treatment-naive pts with NSCLC harboring activating EGFR mutations (L858R and/or ex19del) received oral nazartinib 150 mg QD on a continuous schedule. Primary objective was antitumor activity (overall response rate [ORR] per RECIST v1.1) per blinded independent review committee. Secondary objectives included characterization of safety/tolerability and pharmacokinetics.

Results

At data cutoff (22 March 2018), 45 pts were enrolled; median age 64 years, 62% Asian, 60% female, 58% ECOG PS 1, 18/45 pts (40%) had baseline brain metastases (BM). EGFR mutations were 56% ex19del, 40% L858R, 4% other. Of 45 pts, 12 discontinued nazartinib due to progressive disease (n = 9), adverse events (AEs; maculopapular rash [n = 1]), patient choice (n = 1), or death (n = 1). Median duration of exposure was 43.3 weeks. Frequent AEs (any grade ≥ 20%) regardless of causality were diarrhea (38%), maculopapular rash (31%), stomatitis (24%), cough (22%), decreased appetite (22%), pruritus (20%), and pyrexia (20%). The most frequent grade 3/4 AE (≥ 5%) regardless of cause was maculopapular rash (9%). ORR was 64% (29/45; 95% CI, 49%-78%), including 1 complete response. At data cutoff, responses were ongoing in 27/29 pts; 6-month duration of response rate was 91% (median NE), and 6-month progression-free survival and overall survival rates were 83% and 95%, respectively (medians NE). Disease control rate was 93%. In the 17 pts with baseline BM in nontarget lesions, 9 pts (53%) showed resolution of BM; 1/27 pts without baseline BMs had a new BM post-baseline.

Conclusions

Nazartinib demonstrated a tolerable safety profile and promising efficacy, with durable responses in treatment-naive pts with advanced EGFR-mutant NSCLC, including pts with baseline BM.

Clinical trial identification

EUDRACT number 2013-004482-14

NCT02108964

Release date: 07-Apr-2017

Editorial Acknowledgement

Editorial assistance was provided by Zareen Khan of ArticulateScience Ltd.