China-based biopharmaceutical company Ascentage Pharma (HKG: 6855) has announced that it has received approval from the Center for Drug Evaluation of the National Medical Products Administration (NMPA) to conduct two separate Phase III clinical studies assessing its investigational drug APG-2449. The trials will evaluate the FAK/ALK/ROS1 tyrosine kinase inhibitor (TKI) in patients with non-small cell lung cancer (NSCLC) who are resistant to or intolerant of second-generation anaplastic lymphoma kinase (ALK) TKIs, and in treatment-naïve patients with ALK-positive advanced or locally advanced NSCLC.
APG-2449, developed by Ascentage Pharma, is an orally-active small molecule FAK inhibitor and a third-generation ALK/ROS1 TKI. It is the first FAK inhibitor to be cleared by the CDE for clinical study in China. In the first-in-human trial, the drug candidate showed preliminary clinical benefit and favorable tolerability in patients with NSCLC who were either second-generation ALK TKI resistant or treatment-naïve. The drug also demonstrated potential inhibitory effects on brain metastases, with its ability to cross the blood-brain barrier confirmed through pharmacokinetics (PK) analysis on cerebrospinal fluid.
Biomarker analysis revealed that the phosphorylated FAK (pFAK) expression in tumor tissues at baseline in patients with NSCLC who were second-generation ALK TKI-resistant were positively correlated with the progress-free survival (PFS) after treatment with APG-2449. This suggests that elevated phosphorylated FAK could be associated with drug resistance to second-generation ALK TKIs. – Flcube.com
