TYK Medicines Inc (Stock Code: 02410.HK) announced today that it has recently submitted a Pre-NDA (New Drug Application) to the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China for its investigational Class 1 new drug, asandeutertinib (TY-9591). This drug is expected to become the world’s first third-generation EGFR-TKI targeting non-small cell lung cancer (NSCLC) patients with brain metastases.

This Pre-NDA submission is based on the outstanding results of the TYKM1601202 study (ESAONA), a prospective, multicenter, randomized, active-controlled, pivotal registrational study. The study aimed to evaluate the efficacy and safety of asandeutertinib compared to osimertinib in first-line treatment of NSCLC patients with brain metastases. Led by Professor Yuankai Shi of the Cancer Hospital of the Chinese Academy of Medical Sciences, the study involved a total of 53 centers, including Shandong Cancer Hospital and Hunan Cancer Hospital. For more details on the study, please refer to clinicaltrials.gov, NCT05948813.

As of this submission, the study has enrolled 224 NSCLC patients with EGFR-sensitive mutations and brain metastases. The results showed that asandeutertinib demonstrated a significantly superior intracranial objective response rate (assessed by IRC) compared to osimertinib, the primary endpoint of the study. Additionally, the drug exhibited good safety and tolerability, with no new safety risks identified. Detailed study data will be published at international academic conferences or in peer-reviewed journals.

The NMPA has included asandeutertinib as a conditional approval candidate for the treatment of EGFR mutation-positive NSCLC patients with brain metastases.

Lung cancer is the most common malignancy, with a much higher rate of brain metastasis compared to other tumors. The incidence of brain metastases in treatment-naïve advanced NSCLC patients is 25%-44%, and this cumulative rate increases over time with extended survival. NSCLC patients with EGFR mutations or ALK rearrangements, which are positive driver genes, are at a higher risk and tend to develop brain metastases earlier than those without such mutations. The 3-year cumulative incidence of brain metastases in EGFR-mutated NSCLC patients are 29.4%-60.3%. The median overall survival after brain metastasis in these patients is short, between 7–12 months.

Currently, no third-generation EGFR-TKIs are approved globally for the treatment of NSCLC patients with brain metastases. Asandeutertinib is expected to fulfill a critical unmet clinical need for this patient population.

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