June 23, 2025 – ASK (SZ Stock Symbol: 002755) announced that the Phase III clinical study results of its innovative drug, Lierutinib Tablets (Aoyixin?), have been published in the medical journal 《The Lancet Respiratory Medicine》 (Impact Factor: 32.8). Aoyixin? is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) indicated for the first-line and second-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations.
The published clinical study, led by Professor Shi Yuankai from The Cancer Institute and Hospital, CAMS and involved 56 Chinese clinical centers. This multicenter, randomized, double-blind, active-controlled Phase III clinical study aimed to compare the efficacy and safety of Lierutinib versus Gefitinib for first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR sensitive mutations. Eligible patients were aged 18 years or older, histologically confirmed to have locally advanced or metastatic NSCLC, and confirmed to have EGFR exon 19 deletion or exon 21 (L858R) substitution mutations. Patients were randomly assigned in a 1:1 ratio, with the experimental group receiving oral Lierutinib (80mg twice daily) and the control group receiving oral Gefitinib (250mg once daily) until disease progression or until withdrawal criteria were met. The primary study endpoint was independent review committee (IRC)-assessed progression-free survival (PFS).
From June 30, 2021 to September 22, 2022, a total of 595 patients were screened, with 337 patients randomly assigned to the Lierutinib group (N=168) or the Gefitinib group (N=169). All 337 patients were included in the full analysis set.
· As assessed by the IRC (Independent Review Committee), the median PFS in the Lierutinib group was 20.7 months, significantly superior to the Gefitinib control group (9.7 months). The hazard ratio (HR) was 0.44 (P<0.0001), representing the lowest HR value among disclosed clinical data of similar drugs (lower HR indicates greater benefit). Compared to the control group, Lierutinib effectively reduced the risk of disease progression or death by 56%.
· Subgroup analyses showed that the Lierutinib group demonstrated significant benefits over the Gefitinib group across all subgroups, regardless of age, gender, smoking history, ECOG PS score, EGFR mutation type, or brain metastasis status.
· Brain metastasis is one of the more common metastatic sites in EGFR-mutated NSCLC patients. Due to the special nature of this metastatic site, advanced NSCLC with brain metastases presents clinical treatment challenges. In this clinical trial, among patients with measurable central nervous system (CNS) metastatic lesions, the median CNS PFS in the Lierutinib group was 20.7 months, significantly higher than the Gefitinib control group (7.1 months). The HR was 0.28 (P=0.014), with the median CNS PFS HR value also being the lowest among similar drugs in comparable clinical studies (lower HR indicates greater benefit). Compared to the control group, Lierutinib effectively reduced the risk of intracranial progression or death by 72%.
· Lierutinib demonstrated an overall favorable safety profile, with no new safety signals observed during the study. Common adverse reactions to Lierutinib included diarrhea and rash, mostly grade 1-2. The proportion of patients requiring dose interruption or adjustment was low, allowing for continuous treatment, with a permanent discontinuation rate of 2%—the lowest rate among similar drugs in comparable clinical studies. Additionally, compared to similar domestic drugs, Lierutinib showed lower hepatotoxicity, with ALT elevation and AST elevation rates of 16% and 18%, respectively.
Professor Shi Yuankai stated: "The research team overcame numerous difficulties during the pandemic to ensure high-quality conduct of the clinical study; rigorous trial design, precise patient selection, and meticulous data analysis ensured the completeness, reliability, and scientific validity of the study results. The publication of these results in The Lancet Respiratory Medicine marks high recognition of the Lierutinib clinical study by the international academic community. The study results show that Lierutinib demonstrates significant efficacy and safety in patients with EGFR-sensitive mutation-positive advanced NSCLC receiving first-line treatment, with particularly outstanding efficacy in brain metastases. We believe Lierutinib will provide new treatment options for EGFR-positive NSCLC patients and offer valuable successful experience for subsequent lung cancer drug development."
Mr.Ma Jingfei, CEO of ASK, stated: "The publication of Lierutinib's first-line treatment study results in the international authoritative journal The Lancet Respiratory Medicine not only reflects international recognition of high-quality clinical research achievements of Chinese innovative drugs but also marks a new breakthrough in the field of advanced non-small cell lung cancer treatment by China's self-developed third-generation EGFR TKI. As a structurally differentiated novel third-generation EGFR TKI, Lierutinib extends patients' progression-free survival while improving their quality of life, contributing to the chronic disease management of lung cancer. We look forward to working closely with our partner Innovent Biologics to enable more lung cancer patients to benefit from Lierutinib treatment."