The National Medical Products Administration (NMPA) has recently approved the launch of Mefatinib Maleate tablets in China for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) exon 21 L858R substitution. Developed by Huadong Medicine’s wholly owned subsidiary, Zhongmei Huadong, Mefatinib is a Category 1 innovative drug with independent intellectual property rights, representing a new domestic targeted therapy option for this mutation subtype.

Mefatinib (No. 1639014-72-4) is an oral, potent, and highly selective next-generation irreversible EGFR/HER2 tyrosine kinase inhibitor (TKI). It exerts its antitumor effect by covalently binding to the kinase domains of EGFR (ErbB1) and HER2 (ErbB2), blocking the autophosphorylation process of tyrosine kinases and subsequently suppressing downstream ErbB signaling pathways, thereby inhibiting tumor cell proliferation.

The approval was primarily supported by data from the multicenter, randomized, double-blind, double-dummy Phase III registrational study HDHY-MHTN-III-1907 (CTR20192297). The trial compared Mefatinib head-to-head with the first-generation EGFR-TKI gefitinib in patients with advanced non-squamous NSCLC harboring EGFR-sensitizing mutations, with progression-free survival (PFS) as the primary endpoint. Results presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated a significant PFS improvement with Mefatinib. Median PFS (mPFS) reached 13.7 months versus 9.7 months for gefitinib, with a hazard ratio (HR) of 0.68. In the L858R mutation subgroup, the benefit was more pronounced, with mPFS of 13.7 months versus 8.3 months (HR 0.55), approaching the efficacy observed with approved third-generation EGFR-TKIs. Overall survival (OS) data are still maturing.

Lung cancer remains the leading cause of cancer incidence and mortality in China and worldwide, with NSCLC accounting for approximately 85% of cases. Among Chinese patients with lung adenocarcinoma, EGFR mutations are highly prevalent, affecting roughly 50%. Exon 19 deletions and exon 21 L858R substitutions represent over 70% of all EGFR alterations. Compared with 19del, patients with L858R mutations generally respond less favorably to first-, second-, and even third-generation EGFR-TKIs, and most previous trials failed to show a clear OS benefit, highlighting a continued unmet clinical need.

Industry observers expect that the approval of Mefatinib may help address this treatment gap. The drug has demonstrated a more favorable tolerability profile than some marketed second-generation EGFR-TKIs, supporting its role as a new first-line option for patients with the L858R mutation. Studies have also shown that upon disease progression after Mefatinib treatment, approximately 40% of patients develop an EGFR T790M resistance mutation, making them eligible for subsequent therapy with third-generation EGFR-TKIs and enabling a more rational treatment sequence. Beyond common EGFR mutations, Mefatinib also shows promise for rare EGFR variants. In 2023, it was granted “Breakthrough Therapy Designation” by the Center for Drug Evaluation (CDE) for first-line treatment of advanced NSCLC with S768I, L861Q, or G719X mutations, with ongoing clinical development.

Key patent information for Mefatinib is summarized below: