Tolerability and antitumor activity of ASP8273 in TKI-naive Japanese subjects with EGFR mutation–positive non-small cell lung cancer.

Abstract

9037 Background: EGFR-activating mutations (eg, exon 19 deletions [ex19del], L858R) occur in ~50% of East Asian patients with non-small cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitor (TKI) treatment. ASP8273, an orally administered EGFR TKI that inhibits EGFR-activating mutations, has demonstrated clinical activity in subjects with EGFR mutation-positive (EGFRmut+) NSCLC. Methods: EGFR TKI-naïve adult subjects (≥20 yr) with EGFRmut+ NSCLC were enrolled in this single arm Phase 2 study conducted in Japan (NCT02500927). Subjects received open-label ASP8273 300 mg once daily until discontinuation criteria were met. Primary endpoint was tolerability; secondary endpoint was antitumor activity defined by RECIST v1.1. Results: A total of 31 Japanese subjects (12 M/19 F; median age 64 years [range: 31–82]) were enrolled. Based on local testing, 27 subjects had an ex19del (n = 13, 42%) or a L858R (n = 14, 45%) EGFR activating mutation; 4 subjects (13%) had other EGFR activating mutations (L861Q [n = 2], G719X [n = 2]). ASP8273 300 mg had tolerable adverse events with diarrhea and peripheral neuropathy being most common; no interstitial lung disease events were reported (Table). Across all 31 subjects, based on investigator assessment, treatment with 300 mg ASP8273 was associated with an overall response rate (ORR) of 52%, disease control rate (DCR) of 94%, and a median duration of progression-free survival (PFS) of 11.3 months (95% CI: 7.2, 15.5). In subjects with ex19del, ASP8273 300 mg was associated with an ORR of 46% and DCR of 85%; median PFS was 8.3 months (95% CI: 2.9, -). In subjects with the L858R, ASP8273 300 mg was associated with an ORR of 57% and DCR of 100%; median PFS was 15.5 months (95% CI: 7.2, 15.5). Conclusions: Once-daily ASP8273 300 mg was tolerable in TKI-naïve Japanese subjects with EGFRmut+ NSCLC and demonstrated antitumor activity. Clinical trial information: NCT02500927. [Table: see text]