Recently, Henlius successfully hosted an in-person clinical investigator meeting for the HLX22-GC-301 study in Tokyo, Japan. The meeting focused on the international phase 3 clinical trial (HLX22-GC-301) of HLX22, our innovative anti-HER2 monoclonal antibody (mAb), in combination with trastuzumab and chemotherapy for the first-line treatment of HER2-positive advanced gastric cancer. As Henlius' inaugural in-person investigator meeting in Japan, it brought together over 50 leading Japanese oncologists and clinical researchers from more than 20 clinical sites in Japan, and Henlius team. Together, they explored the clinical advantages of HLX22 as a potential First-in-Class candidate and discussed strategies for its development in Japan. This meeting marks a significant step in our commitment to deepening our presence in Japan and underscores our determination to drive global market impact through high-quality innovation.
Dr. Ken Kato, National Cancer Center, Department of Gastrointestinal Medical Oncology remarked, "This meeting was highly productive, fostering dynamic and forward-thinking discussions. The successful execution of this trial hinges on the dedication and collaboration of investigators at participating sites, and I am confident that our collective efforts will lead to meaningful advancements."
Dr. Hiroshi Imamura, Toyonaka Municipal Hospital, Department of Gastroenterology remarked, "It was a privilege to participate in today’s meeting, which offered invaluable insights into the trial. While I had thoroughly reviewed the protocol beforehand, the discussions further enhanced my understanding and deepened my engagement with the study. We remain fully committed to advancing patient enrollment at our institution."
Gastric cancer is a highly prevalent malignancy in Japan, with incidence and mortality rates significantly exceeding the global average. Japan ranks second in the number of new cases and third in the number of deaths globally[1]. The majority of patients with gastric/gastroesophageal junction (G/GEJ) cancer are diagnosed at an advanced stage, resulting in a poor overall prognosis, with a 5-year survival rate of only 6% [2,3]. Among these patients, approximately 12% to 23% are HER2-positive, and their prognosis is worse than that of HER2-negative patients[2,4]. Currently, the standard first-line treatment for HER2-positive locally advanced or metastatic G/GEJ cancer is trastuzumab in combination with chemotherapy. For patients who are PD-L1-positive (PD-L1 CPS ≥1), some guidelines also recommend the addition of immunotherapy. However, sustained efficacy and prognosis still require further improvement[5]. Globally, no dual HER2-targeted therapy has been approved for the treatment of HER2-positive gastric cancer.
HLX22, an innovative anti-HER2 mAb, can bind to HER2 extracellular subdomain IV at a binding site different from that of trastuzumab, which allows simultaneous binding of HLX22 and trastuzumab to HER2 dimers (HER2 homodimer and HER2/EGFR heterodimer) on tumor cell surface, thereby promoting the internalization and HER2 dimer degradation. Clinical data on the combination of HLX22 and HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe) demonstrate that the addition of HLX22 to HANQUYOU® plus chemotherapy significantly improves survival and anti-tumor efficacy in first-line treatment of HER2-positive G/GEJ cancer patients, with manageable safety profiles[6-8]. The HLX22-GC-301 study aims to evaluate the efficacy and safety of HLX22 in combination with trastuzumab and chemotherapy for the first-line treatment of patients with HER2-positive metastatic gastric/gastroesophageal junction cancer (GC/GEJC). The Investigational New Drug (IND) application for this study has been approved by the National Medical Products Administration (NMPA) in China and the U.S. Food and Drug Administration (FDA), and the study has been initiated in multiple countries and regions worldwide. Japan, as one of the key countries of HLX22-GC-301 study, will play a vital role in patient enrollment and ensuring the quality of clinical data. This in-person investigator meeting, through in-depth discussions, has further clarified the patient population characteristics, diagnostic and treatment standards, as well as clinical trial protocol in Japan, laying a solid foundation for the efficient advancement of the study.
Jing Li, General Manager of Global Product Development at Henlius, stated: "Japan bears a significant burden of gastric cancer but has a well-established clinical research system, making it a crucial fulcrum for the global development of HLX22. We look forward to closely collaborating with local researchers to provide better treatment options for patients."
In addition to the HLX22-GC-301 study, the company is also actively advancing the clinical research of more innovative pipeline products in Japan, a key market for biologics. In 2024, Henlius initiated the phase 3 stage of the international multi-centre clinical trial (ASTRUM-015) for serplulimab in patients with metastatic colorectal cancer (mCRC) in Japan and has enrolled the first Japanese patient. The concurrent advancement of these two Phase 3 studies targeting high-incidence gastrointestinal tumors in Japan not only highlights Henlius' international clinical development capabilities but also provides crucial support for the future registration and launch of pipeline products in Japan and globally.
Jin Li, General Manager of Regulatory Affairs at Henlius, said: "Japan is one of the core markets in our global strategy. We will leverage our robust clinical data and efficient implementation capabilities to bring innovative therapies to local patients as soon as possible."
Looking forward, Henlius will continue to deepen its global market presence, centering on patient needs and driving the development of more innovative therapies. We remain committed to our mission of " To improve patients' lives by timely providing them with quality and affordable protein therapeutics through technical innovation and operational excellence. "
【Reference】
[1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35.
[2] Ajani JA. et al. J Natl Compr Canc Netw 2022;20(2):167-92.
[3] Alsina M. et al. Nat Rev Gastroenterol Hepatol 2023;20(3):155-70.
[4] Gravalos C. et al. Ann Oncol 2008;19(9):1523-9.
[5] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.1.2024
[6] Zhu X, Ding Y, Wang Q, Yang G, Zhou L, Wang Q. HLX22, an anti-HER-2 monoclonal antibody, in patients with advanced solid tumors overexpressing human epidermal growth factor receptor 2: an open-label, dose-escalation, phase 1 trial. Invest New Drugs. 2023;41(3):473-482. doi:10.1007/s10637-023-01338-7
[7] Jin Li et al., HLX22 plus HLX02 and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer: A randomized, double-blind, multicenter phase 2 study.. JCO 42, 354-354(2024).DOI:10.1200/JCO.2024.42.3_suppl.354
[8] J. Li et al., 422P HLX22 plus HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric/gastroesophageal junction cancer: Updated results from a randomized, double-blind phase II study, Annals of Oncology,Annals of Oncology (2024) 35 (suppl_1): S162-S204. 10.1016/annonc/annonc1482