Nazartinib (EGF816) in patients with treatment-naïve EGFR-mutant non-small cell lung cancer (NSCLC): Updated phase II results.

Abstract

9574 Background: Prior data from a phase I/II study showed durable responses, including efficacy in brain lesions, and a tolerable safety profile with nazartinib in treatment (tx)-naïve patients (pts) with EGFR-mutant (mut), locally advanced (adv)/metastatic NSCLC. Here we report updated phase II results, including overall survival (OS). Methods: Tx-naïve adult pts with activating EGFR-mut (L858R or ex19del), stage IIIB/IV adv NSCLC with neurologically stable and controlled brain metastasis (BM) received oral nazartinib 150 mg once daily (continuous schedule). Primary endpoint: overall response rate (ORR) by BIRC per RECIST v1.1; secondary endpoints: disease control rate (DCR), duration of response (DOR), time to response, progression-free survival (PFS), OS, and safety. Results: At data cut-off (Nov 1, 2019), 45 pts were enrolled (median [range] age: 64 [28–83] years; 26 pts [58%] ECOG PS 1; 18 pts [40%] had baseline BM). EGFR mutations: 56% ex19del, 40% L858R, 4% other. 26/45 pts (58%) discontinued tx, with the primary reason being progressive disease in 19 pts (42%); 2 pts (4%) discontinued tx due to AEs. Median (range) follow-up for OS: 25 (0–33) months (mo); and for PFS: 17 (0–33) mo. ORR by BIRC: 69%; median PFS by BIRC: 18 mo; median OS was NE and at 33 mo, 56% of pts were alive (Table). BIRC results by baseline BM are shown in the Table. Median (range) duration of exposure: 24 (0–34) mo. Most frequent AEs (≥20% all grade, all causality): diarrhea (47%), maculopapular rash (38%), pyrexia (29%), cough and stomatitis (27% each), decreased appetite and pruritus (24% each), and dermatitis acneiform (22%). Most frequent grade 3/4 AEs (≥10%, all causality): maculopapular rash (5 pts [11%]; all grade 3) and increased lipase (5 pts [11%]; 1 pt with grade 4; no clinical pancreatitis AE was observed). Conclusions: After additional follow-up, median OS was still not reached and the safety profile was manageable. Nazartinib is a promising 3rd generation EGFR TKI for tx-naïve pts with adv EGFR-mut NSCLC, including pts with baseline BM. Clinical trial information: NCT02108964 . [Table: see text]