Abstract CT212: Neratinib efficacy in second line patients with EGFR exon 18-mutant non-small-cell lung cancer

Abstract Background: In NSCLC patients, mutations in EGFR exon 18 account for approximately 3-5% of all EGFR mutations and are associated with a poor prognosis. In phase 2 SUMMIT global basket trial, 29 metastatic NSCLC patients with EGFR exon 18 mutations received neratinib monotherapy in global. The objective response rate (ORR) was 35%. However, only 1 (4.5%) Asian individual enrolled in this study. Therefore, there is an urgent need to explore the effect of neratinib in Chinese NSCLC patients with EGFR exon 18 mutation. Methods: Neratinib was approved with brand Hannaijia in 2024 in China. Planned 14 patients with EGFR exon 18-mutated NSCLC who had failed first-line standard chemotherapy were enrolled in this study (NCT06029816) . The primary endpoint of this phase 2 study is the ORR by the investigator according to RECISTv1.1 and the secondary endpoints are including DCR (Disease Control Rate), PFS (Progression-Free Survival). Results: To date, 14 advanced NSCLC patients with exon 18 mutations after receiving Neratinib (Hannaijia®) treatment following the failure of standard first-line therapy. Overall, ORR was 64.3% (9 PR ,4 SD,1 PD). The disease control rate was 92.9% (13 patients). The median PFS was 12.78 months (95% Cl,5.62 months to NE). The common 1-2 grade treatment-related adverse events (AEs) occur in 100% of patients. Diarrhea (CTCAE Grade 2-3) was the most common, which occurred in 50.0% of patients, and can be managed within 3 days after loperamide intervention. To date, there have been no grade 4- 5 AEs in any of the patients. Conclusion: Neratinib (Hannaijia®) treatment following the failure of standard first-line therapy demonstrated tolerable safety and encouraging preliminary efficacy in NSCLC with EGFR exon 18 mutations. This study is expected to provide more treatment options for Chinese patients with NSCLC who have EGFR exon 18 mutations. Citation Format: Steve Shen, Wenfeng Fang, Ning Li, Runxiang Yang, Ying Cheng, Baogang Liu, Haiyong Wang, Lin Wu, Qiming Wang. Neratinib efficacy in second line patients with EGFR exon 18-mutant non-small-cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT212.