China's CDE Approves Phase III Trials of APG-2449 for NSCLC

ROCKVILLE, Md. and SUZHOU, China, Oct. 7, 2024 — Ascentage Pharma, a global biopharmaceutical firm focused on addressing unmet medical needs, particularly in cancer treatments, announced today that their drug APG-2449 has received approval from China's National Medical Product Administration (NMPA) to proceed to two Phase III clinical trials. APG-2449 is a tyrosine kinase inhibitor (TKI) targeting FAK/ALK/ROS1 and will be evaluated in patients with non-small cell lung cancer (NSCLC).

The first of these Phase III trials aims to assess the efficacy and safety of APG-2449 as compared to platinum-based chemotherapy in NSCLC patients who have developed resistance or intolerance to second-generation ALK TKIs. The second trial will compare APG-2449 against crizotinib as a first-line treatment in patients with advanced or locally advanced ALK-positive NSCLC. Both studies are pivotal and multicenter, open-label and randomized, focusing on an investigational drug not yet approved by the FDA in the United States.

ALK-positive NSCLC, which accounts for about 3-5% of all lung cancers, is characterized by rearrangements in the ALK gene. This type of cancer is often found in younger, non-smoking individuals and carries a higher risk of brain metastasis. Despite existing ALK-targeted therapies, over 50% of patients treated with second-generation ALK TKIs develop resistance to these treatments. Therefore, the Chinese Society of Clinical Oncology (CSCO) recommends platinum-based chemotherapy for patients who no longer respond to second-generation ALK TKIs. However, chemotherapy often results in severe side effects, creating a demand for new, effective, and safer therapies.

Developed by Ascentage Pharma, APG-2449 is an orally-active small molecule and the first focal adhesion kinase (FAK) inhibitor to receive clearance for clinical studies in China. Early trials have shown that APG-2449 provides clinical benefits and is well-tolerated in NSCLC patients who are either resistant to second-generation ALK TKIs or are treatment-naive. The drug has also demonstrated potential in inhibiting brain metastases by crossing the blood-brain barrier, as confirmed through pharmacokinetic (PK) analysis on cerebrospinal fluid. Biomarker analysis suggests that elevated levels of phosphorylated FAK (pFAK) in tumor tissues may be linked with progression-free survival (PFS) in patients treated with APG-2449, indicating a possible connection between drug resistance and high pFAK levels.

Prof. Li Zhang, the principal investigator from Sun Yat-sen University Cancer Center, noted that APG-2449 is a potent multitargeted inhibitor that has shown promise in previous clinical data. He expressed optimism about the drug's preliminary efficacy in patients resistant to second-generation ALK TKIs and looks forward to further validating APG-2449 through the upcoming Phase III studies.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, emphasized the significant unmet clinical needs in NSCLC. He mentioned that the NMPA's approval for the Phase III trials is a major milestone for APG-2449's clinical development and highlighted the company's commitment to advancing these studies to benefit more patients.

Ascentage Pharma has a diverse pipeline of innovative drug candidates targeting various pathways and is actively involved in numerous clinical trials worldwide. The company aims to strengthen its research and development capabilities to continue addressing unmet medical needs globally.