Overview
TY-4028, a targeted therapy for non-small cell lung cancer (NSCLC) with EGFR/HER2 exon 20ins mutations, was independently developed by TYK Medicines, Inc. This novel and effective treatment is administered orally and aims to treat locally advanced or metastatic NSCLC. The preclinical study results showed that TY-4028 displayed superior anti-tumor efficacy against EGFR/HER2 exon 20ins in vivo animal models. Furthermore, the pharmacokinetics and safety evaluation study revealed a favorable druggability and safety profile for TY-4028. In April 2023, TY-4028 received the SMP letter from the FDA, and in June 2023, it obtained approval of the clinical trial notice from the CDE.
Mechanism of Action
The epidermal growth factor receptor (EGFR) activation has been identified as a major contributing factor in the development of non-small cell lung cancer (NSCLC). Approximately 30% of NSCLC patients possess EGFR-activating mutations, with a subset of these oncogenic mutations, accounting for 4-10% of the EGFR mutation spectrum, being EGFR exon 20 insertion mutations. Genetic pathology further demonstrates that 2% of NSCLC patients present with hotspot mutations in the HER2 gene, a homologous member of the EGFR family known to play a pivotal role in breast cancer tumorigenesis through mutational evolution. Of note, over 90% of the HER2 mutations found in NSCLC are exon 20 insertion mutations. Despite the availability of FDA-approved first, second, and third-generation EGFR inhibitors and immunotherapy, these treatments have proven ineffective in treating NSCLC harboring EGFR exon 20ins mutations in the clinical setting. Additionally, trastuzumab and EGFR-TKIs exhibit limited efficacy in treating NSCLC patients with HER2 exon 20ins mutations. There is evidence to suggest that TY-4028 has the potential to address the unmet medical needs of NSCLC patients with EGFR/HER2 exon 20ins mutations or HER2 exon 20ins mutations.
