Abstract 66P
Background
Limertinib (ASK120067) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both sensitizing EGFR and EGFR T790M mutations. In a phase IIb study, limertinib exhibited promising efficacy in patients who progressed after first- or second-generation EGFR TKIs. Here, we report mature OS data and conducted a post-hoc analysis to further assess the efficacy and safety of reduced-dose limertinib.
Methods
In the phase IIb study, patients received limertinib 160 mg orally twice daily until disease progression or unacceptable toxicity. Participants were categorized into those who received dose reduction and those who did not. Progression-free survival (PFS), overall survival (OS) were compared between the subgroups. Statistical analyses for patients in the reduced-dose and standard-dose limertinib groups were post hoc and considered exploratory.
Results
A total of 301 patients were enrolled. As of the cut-off date on Jun 27, 2023, the median follow-up was 28.5 months. Median PFS and OS were 11.0 months (95%CI: 9.7–12.4) and 28.1 months (95%CI: 24.3–31.7), respectively. 87 patients experienced dose reduction from 160 mg to 80 mg twice daily due to AEs. Baseline characteristics were balanced between reduced-dose group and standard-dose group. Median PFS was 13.7 months (95%CI:11.0–16.6) in the reduced-dose group and 10.2 months (95%CI:8.4–11.6) in the standard-dose group (HR=0.69; 95% CI:0.50–0.96; P=0.0240). The median OS was 42.5 months (95% CI:32.6-NE) and 25.0 months (95%CI:18.6–28.3), respectively (HR=0.51; 95%CI:0.35–0.76; P=0.0008). The most frequently reported adverse events leading to dose reduction were diarrhea (50.6%) and rash (6.9%).
Conclusions
Long-term follow-up results support the potential of Limertinib (ASK120067) as a promising treatment for EGFR T790Mmutated NSCLC. Reduced-dose limertinib demonstrated encouraging survival outcomes and is worthy of further investigation.
Clinical trial identification
NCT03502850.
Legal entity responsible for the study
Jiangsu Aosaikang Pharmaceutical Co. Ltd.
Funding
Jiangsu Aosaikang Pharmaceutical Co. Ltd.
Disclosure
All authors have declared no conflicts of interest.