Firmonertinib (AST-2818): A Comprehensive Clinical and Pharmacological Monograph on a Third-Generation EGFR Tyrosine Kinase Inhibitor

Executive Summary

Firmonertinib (AST-2818) is an orally available, third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that represents a significant advancement in the targeted therapy of non-small cell lung cancer (NSCLC). Developed by Shanghai Allist Pharmaceuticals and co-developed globally by ArriVent Biopharma, firmonertinib is engineered for high potency and selectivity against both EGFR-sensitizing mutations and the key T790M resistance mutation, while sparing wild-type EGFR. This molecular profile translates into a favorable therapeutic window, mitigating common toxicities associated with earlier-generation TKIs.

The clinical development program for firmonertinib has yielded robust evidence supporting its efficacy and safety across multiple lines of therapy. In the second-line setting for patients with EGFR T790M-positive NSCLC who have progressed on prior TKIs, the pivotal Phase IIb study (NCT03452592) demonstrated a compelling objective response rate (ORR) of 74% and a median progression-free survival (PFS) of 9.6 months. A noteworthy finding from this trial was the significant survival benefit observed in patients who continued treatment beyond initial radiological progression, suggesting a durable disease control mechanism.