Live from ASCO 2024 | Ascentage Pharma Updates APG-2449 Data in NSCLC Patients

Ascentage Pharma, a global biopharmaceutical company, announced new data from its novel drug candidate APG-2449 at the 60th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. Ascentage Pharma, known for developing treatments for cancer, chronic hepatitis B, and age-related diseases, has presented at ASCO for seven consecutive years. This year, four clinical studies of three proprietary drug candidates, including APG-2449, were selected for presentation.

The ASCO Annual Meeting is a prestigious event that highlights the latest in clinical oncology research and cutting-edge cancer therapies. During this event, Ascentage Pharma shared updated data on APG-2449, a tyrosine kinase inhibitor (TKI) that targets FAK, ALK, and ROS1. The data demonstrated the drug’s preliminary efficacy in non-small-cell lung cancer (NSCLC) patients who were either TKI naïve or resistant to second-generation ALK TKIs, with notable antitumor activity observed in cases of brain metastases.

Prof. Li Zhang, the principal investigator from Sun Yat-sen University Cancer Center, highlighted the promising results of APG-2449. Zhang emphasized that the study showed manageable safety and favorable antitumor activity, particularly in patients resistant to second-generation ALK TKIs. The multitargeted inhibition approach combining FAK and ALK inhibitors may provide a new management strategy for NSCLC patients. Zhang expressed hope that Ascentage Pharma would continue to advance APG-2449 to benefit more patients.

Dr. Yifan Zhai, Ascentage Pharma's Chief Medical Officer, reiterated the significance of the findings, indicating that APG-2449 could offer renewed hope to NSCLC patients resistant to existing ALK inhibitors. Zhai underscored the company's commitment to addressing unmet clinical needs globally and advancing the development of safe and effective treatments.

The study included both dose-escalation and dose-expansion components, determining a recommended phase 2 dose (RP2D) of 1,200 mg daily. As of April 2, 2024, 144 patients with NSCLC, mesothelioma, or ovarian cancer had been treated with APG-2449, with the median age being 53 years.

The efficacy results showed that APG-2449 had an overall response rate (ORR) of 68.2% in ROS1+ and 78.6% in ALK+ TKI-naïve NSCLC patients. In patients resistant to second-generation ALK inhibitors, 45.5% achieved partial responses. Additionally, among patients with brain metastases, an intracranial ORR of 75.0% was observed.

Biomarker analysis revealed that responses to APG-2449 correlated with levels of phosphorylated FAK (pFAK) in tumor tissues and reductions in pFAK levels in peripheral blood mononuclear cells (PBMCs).

The safety profile indicated that 89.6% of patients experienced treatment-related adverse events (TRAEs), with the most common being elevated serum creatinine, increased liver enzymes, nausea, vomiting, diarrhea, and rashes. Grade 3 or higher TRAEs were reported in 13.9% of patients.

In conclusion, APG-2449 has shown preliminary efficacy and an acceptable safety profile in NSCLC patients, particularly those resistant to second-generation ALK inhibitors. The biomarker analysis supports the potential of APG-2449 as a therapeutic option, correlating pFAK levels with patient responses. Continued development and further studies are anticipated to bring this promising treatment to more patients.

Ascentage Pharma is a biopharmaceutical company dedicated to developing novel cancer therapies, chronic hepatitis B treatments, and solutions for age-related diseases. The company is involved in over 40 Phase I/II clinical trials globally and has a robust pipeline of drug candidates targeting key apoptosis regulators. With numerous partnerships and a focus on unmet clinical needs, Ascentage Pharma aims to advance innovative treatments for patients worldwide.