Epitinib Succinate

Non-small-cell lung cancer (NSCLC) had poor prognosis in patients with brain metastasis. The trial evaluated the safety and efficacy of epitinib (HMPL-813), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), for EGFR-mutant NSCLC with brain metastasis.

This open-label, dose-expansion phase Ib study (ClinicalTrials.gov: NCT02590952) was conducted at 7 Chinese centers and enrolled patients with EGFR-mutant advanced NSCLC with brain metastasis. Epitinib was administered at 120 mg or 160 mg, orally QD. The primary endpoint was safety and tolerability.

Between April 2015 and April 2019, 72 patients were enrolled and received epitinib at 120 mg (n = 30) or 160 mg (n = 42). Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 13 (43.3%) patients in 120 mg group and 21 (50.0%) in 160 mg group. The objective response rate (ORR) was 53.6% (95% CI 33.9%-72.5%) in 120 mg group and 40.5% (25.6%-56.7%) in 160 mg group. The median duration of response in the 120 mg and 160 mg groups were 7.40 months (95% CI 3.70-7.40) and 9.10 months (6.50-12.00), respectively. The median progression-free survival were 7.40 months (95% CI 5.40-9.20) and 7.40 months (5.50-10.00), respectively.

In patients with EGFR-mutant NSCLC with brain metastasis, epitinib was well tolerable with a promising efficacy. According to the comprehensive assessment on safety and efficacy, 160 mg QD could be the recommended phase 2 dose.