Alpha Biopharma Hosts Expert Advisory Meeting in Shanghai for Zorifertinib (AZD3759), a Breakthrough EGFR-TKI for NSCLC with CNS Metastases

Shanghai, January 7, 2020/PRNewswire/ -- Alpha BiopharmaAlpha Biopharma (hereinafter referred to as “Chentai Pharma”) held a grand ceremony in Shanghai to announce the chemical name, Zorifertinib, for its lead investigational product (AZD3759). Distinguished experts and company executives attended the expert advisory meeting, including Professor Wu Yilong, Lifetime Director of Guangdong Provincial People’s Hospital, Honorary Director of Guangdong Lung Cancer Institute, and a top expert in lung cancer; Professor Wang Jie, Director of the Department of Medical Oncology at the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences, and Vice Chairman of the Lung Cancer Committee of the Chinese Anti-Cancer Association; Professor Lu Shun, Director of the Department of Medical Oncology at Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, and Chairman of the Lung Cancer Committee of the Chinese Anti-Cancer Association; Professor Cheng Ying, Party Secretary of Jilin Cancer Hospital, Vice President of the Chinese Society of Clinical Oncology (CSCO), and Chairman of the CSCO Small Cell Lung Cancer Committee; Professor Myung-Ju Ahn from Samsung Medical Center, South Korea; and the management team of Chentai Pharma.

Alpha Biopharma is a clinical-stage biopharmaceutical company dedicated to the research and development of innovative therapies to address unmet clinical needs. To date, Alpha Biopharma has established a robust clinical development team and formulated optimized strategies for innovative drug development. Its management team comprises seasoned executives with extensive multinational experience in clinical operations, regulatory affairs, and pharmaceutical marketing, supported by drug development experts with decades of expertise in oncology therapy and medical research.

Zorifertinib (AZD3759), a flagship investigational drug developed by Alpha Biopharma, is a next-generation small-molecule epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It achieves 100% blood-brain barrier penetration, ensuring equivalent drug concentrations in the blood, brain tissue, and cerebrospinal fluid. It is specifically indicated for the treatment of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) accompanied by central nervous system (CNS) metastases.

In recent years, the development of EGFR-TKI drugs has improved survival outcomes for patients with advanced EGFR mutation-positive non-small cell lung cancer (NSCLC). However, the emergence of drug resistance and central nervous system (CNS) metastases (including brain metastases and leptomeningeal metastases) has become a major cause of treatment failure. Data indicate that as the survival duration of patients with EGFR mutation-positive NSCLC increases, the incidence of CNS metastases is also rising, reaching approximately 50%. These patients generally have a poor prognosis, often accompanied by severe neurological deterioration, reduced quality of life, and limited life expectancy.

Zorifertinib (AZD3759) has undergone the global Phase I BLOOM clinical study targeting patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases. The study enrolled 67 NSCLC patients with CNS metastases from 11 centers across four regions: Australia, South Korea, Taiwan, and the United States. Intracranial, extracranial, and overall efficacy were evaluated separately using modified RECIST 1.1 criteria. The results demonstrated that Zorifertinib (AZD3759) achieved 100% blood-brain barrier penetration in humans, confirming its effective inhibition of CNS metastatic tumors and an acceptable safety profile.

Based on the positive data obtained from the Phase I clinical study, Zorifertinib initiated the EVEREST (AZD3759-003) Phase II/III clinical study in April 2018. In October 2019, the EVEREST study successfully passed the safety data review by the IDMC (Independent Data Monitoring Committee, composed of clinical medicine experts, clinical research experts, pharmacology experts, and independent statisticians) meeting, which recommended continuing the trial. The study is currently in the active enrollment phase.

At the expert advisory meeting, as investigators of the EVEREST study, numerous renowned experts in the field of lung cancer engaged in vigorous discussions on the progress of the EVEREST study and the development strategy for Zorifertinib.

As the Global Leading PI of the EVEREST study, Professor Wu Yilong first clarified the treatment consensus for EGFR mutation-positive NSCLC with CNS metastases at the conference: “Based on the results of the BRIAN study, it has been confirmed that EGFR-TKI therapy is superior to whole-brain radiotherapy for patients with EGFR mutation-positive NSCLC and CNS metastases. Therefore, the consensus we have reached is that once brain metastases occur in patients with EGFR mutations, EGFR-TKI drugs should be used as the first-line treatment.””

Professor Myung-Ju Ahn, the global leading Principal Investigator (PI) for the Phase I BLOOM study of zorifertinib and the Korean leading PI for the EVEREST study, presented the results of the BLOOM study at the conference. She stated, “Most EGFR-TKI drugs are substrates of P-gp and BCRP, efflux proteins of the blood-brain barrier. Zorifertinib is the first next-generation EGFR-TKI specifically designed to achieve 100% blood-brain barrier penetration. It demonstrates favorable efficacy in both intracranial and extracranial lesions, with an adverse event profile similar to that of other EGFR-TKIs.””

At the conference, Professor Lu Shun, the Principal Investigator (PI) of the EVEREST study, stated, “The EVEREST study is, in fact, a larger-sample Phase II/III randomized controlled trial specifically focused on brain metastases. Its significance lies in the fact that it represents the first head-to-head comparison of the benefits of TKI agents in patients with brain metastases. As is well known, Zorifertinib exhibits superior blood-brain barrier penetration. Therefore, the value of this randomized, prospective clinical study is to determine the differences among TKI agents and clarify whether they can become the standard of care for brain metastases.””

Professor Wang Jie, the leading Principal Investigator (PI) for the EVEREST study in China, stated: “This is a randomized, open-label, Phase II/III study involving 55 research centers worldwide. It aims to compare the efficacy and safety of Zorifertinib monotherapy as first-line treatment versus Gefitinib/Erlotinib in patients with EGFR mutation-positive (L858R and/or Exon 19 Del) advanced non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastases. The study plans to enroll 432 patients. A total of 55 research centers globally will participate, including 41 in China, 9 in South Korea, 4 in Taiwan, China, and 1 in Singapore. This represents the largest prospective clinical study conducted to date focusing on patients with EGFR mutation-positive NSCLC and brain metastases.””

Professor Cheng Ying, the Principal Investigator of the EVEREST study, stated during the conference discussion session: “To date, we have observed promising intracranial and extracranial efficacy with Zorifertinib, which is highly encouraging. We look forward to the final results of the EVEREST study on Zorifertinib. In clinical practice, resistance to EGFR-TKIs accompanied by central nervous system (CNS) metastases, particularly leptomeningeal metastases, remains a key focus and challenge in treatment. Given the mechanism of action of Zorifertinib, we hope to further explore this field in the future to address unmet therapeutic needs.”

Finally, Professor Wu Yilong delivered the conference summary and shared his aspirations for Zorifertinib: “The EVEREST study of Zorifertinib is, to date, the only large-scale, prospective, head-to-head clinical trial conducted globally that specifically targets patients with lung cancer brain metastases. We hope this study will be completed as soon as possible, turning this vision into reality and providing superior therapeutic options for the clinical management of lung cancer brain metastases.”

In recent years, Alpha Biopharma has established a robust clinical development team with extensive experience in China, the United States, Europe, and the Asia-Pacific region. Zorifertinib (AZD3759) is not only a Class 1.1 innovative drug approved by the National Medical Products Administration but also a key project under China’s “Major New Drug Creation” special initiative. Moving forward, Alpha Biopharma will continue to collaborate with multinational pharmaceutical companies and research institutions both domestically and internationally, dedicated to developing innovative therapies that address urgent unmet clinical needs, with the aim of becoming a globally leading and trusted provider of innovative medicines.