In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9572-9572
Abstract:
9572 Background: Lazertinib (YH25448) is a highly mutant-selective, irreversible 3 rd -generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets the activating EGFR mutations (Del19 and L858R), as well as the T790M mutation, while sparing wild type. We report the efficacy and safety results of lazertinib 240 mg as recommended phase 2 dose (RP2D) from a phase I/II study of lazertinib (NCT03046992). Methods: Patients (pts) with advanced NSCLC, who had progressed after prior EGFR-TKI therapy were enrolled in an open-label, multicenter, phase I/II study with dose-escalation (20-320 mg), dose-expansion (40-240 mg) and dose-extension phases. Pts were assessed for safety, tolerability, pharmacokinetics and efficacy. For dose-expansion and extension phases, tumors had to be T790M mutation-positive (T790M+). Of all 78 pts assigned to lazertinib 240 mg dose level across all phases, 76 pts with centrally confirmed T790M+ were included for efficacy analysis. Results: As of 30 Sep 2019, a total of 78 pts (49% female, median age 62) received at least one dose of lazertinib 240 mg. The median duration of follow-up was 9.6 months and 44 pts were ongoing at data cut-off. Of 78 pts, 76 pts with centrally confirmed T790M+ showed the objective response rate (ORR) 57.9% (95% CI 46.8, 69.0), the disease control rate (DCR) 89.5% (95% CI 82.6, 96.4), the median progression-free survival (PFS) 11.0 months (95% CI 5.6, 16.4) and the median duration of response (DoR) 13.8 months (95% CI 9.6, NR) by independent central review (ICR), respectively. Two pts (3%) experienced a confirmed complete response. The investigator-assessed ORR, DCR, median PFS and median DoR were 72.4% (95% CI 62.3, 82.4), 94.7% (95% CI 89.7, 99.8), 13.2 months (95% CI 9.6, not reached) and 11.8 months (95% CI 8.4, not reached), respectively. The most common treatment-emergent adverse events (TEAEs) at the 240 mg dose regardless of its causality were rash (35%), pruritus (33%) and paraesthesia (32%), which were mostly mild (Grade ≥3 rash: 1%; no Grade ≥3 pruritus or paraesthesia). TEAEs leading to dose reduction and dose discontinuation were observed in 13% (10/78) and 8% (4/78), respectively. Drug related TEAEs of grade ≥3 were observed in 6% (5/78). Conclusions: Lazertinib 240 mg has a favorable safety profile, and exhibits promising anti-tumor activity in pts with EGFR T790M+ NSCLC. Clinical trial information: NCT03046992 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.9572
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
