Shanghai, China, April 17,2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient has been dosed in China in HLX22-BC201, a phase 2 clinical trial of the company’s novel anti-HER2 monoclonal antibody (mAb), HLX22, in combination with trastuzumab deruxtecan (T-DXd) for the treatment of HER2-low, hormone receptor (HR)-positive locally advanced or metastatic breast cancer. Apart from its exploration in HER2-positive gastric cancer, the therapeutic scope of HLX22 has further expanded to the field of breast cancer, potentially providing new treatment options for broader tumour patients population.
Breast cancer is the second most diagnosed cancer in the world, according to GLOBOCAN 2022. There were around 2.30 million new cases of breast cancer in 2022 globally, including more than 357,000 in China[1]. Among these, HER2-low breast cancer has been proposed as a novel clinical classification for breast cancers demonstrating IHC 1+ or 2+ with negative ISH results. This category accounts for approximately 45%-55% of all breast cancer cases[2]. Currently, due to the lack of targeted therapies, HER2-low,hormone receptor (HR)-positive breast cancer primarily relies on treatments such as endocrine therapy or chemotherapy[3]. Despite novel regimens like trastuzumab deruxtecan (T-DXd) has demonstrated anti-tumour activity in HER2-low, HR-positive breast cancer[4], therapeutic options for this patient population remain relatively limited, indicating an unmet medical need to explore more safe and effective innovative treatment approaches.
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 tumour cell surface, thereby promoting the internalization and HER2 dimer degradation. The phase 2 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-tumour efficacy in first-line treatment of HER2-positive gastric/gastroesophageal junction cancer (GC/GEJC) patients, with manageable safety profiles[5-7]. At present, the Investigational New Drug (IND) applications for HLX22-GC-301, a phase 3 clinical 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 GC/GEJC, have been approved by regulatory authorities in China, the U.S, Japan and Australia, etc., and this international study has been initiated in multiple countries and regions worldwide and has completed its first patient dosing globally. Furthermore, HLX22 has received orphan drug designation (ODD) in 2025 from the U.S. Food and Drug Administration (FDA) for the treatment of gastric cancer.
Based on the promising results showcased by HLX22 in the field of HER2-positive gastric cancer, Henlius is actively exploring the efficacy of HLX22 in a broader range of solid tumours, continuously expanding the patient groups who can benefit from it. In 2024, the phase 2 clinical trial of HLX22 in combination with trastuzumab and chemotherapy or combined with T-DXd was approved by the China National Medical Products Administration (NMPA) for the treatment of HER2-expressing solid tumours. Preclinical animal studies of HLX22 combined with T-DXd showed synergistic anti-tumour effect and good safety profiles, which may offer more benefits to patients with HER2-expressing tumours. Looking forward, Henlius will also continue to explore the therapeutic potential of its novel anti-HER2 targeted therapies in tumours and efficiently accelerate the global development of HLX22, offering more affordable and effective treatment options for patients worldwide.
About HLX22-BC201
This is a multicenter phase 2 study aimed to evaluate the efficacy and safety of HLX22 combined with trastuzumab deruxtecan for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-low, hormone receptor (HR)-positive locally advanced or metastatic breast cancer who have progressed on or are intolerant to standard therapy. Eligible subjects will receive HLX22 plus trastuzumab deruxtecan. The primary endpoints of this study are objective response rate (ORR) and progression-free survival (PFS) accessed by independent radiology review committee (IRRC) per RECIST 1.1; secondary endpoints include investigator-assessed objective response rate (ORR) and progression-free survival (PFS), overall survival (OS), IRRC or investigator-accessed duration of response (DOR), safety, pharmacokinetics, immunogenicity, and biomarkers.
References
[1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35.
[2] Tarantino, P., et al. (2021). HER2-Low Breast Cancer: Pathological and Clinical Perspectives. Journal of Clinical Oncology, 39(15), 3205-3214.
[3] Gennari, A., et al. (2022). HER2-Low Breast Cancer: A New Entity with Therapeutic Implications. Nature Reviews Clinical Oncology, 19(6), 325-336.
[4] Modi, S., et al. (2022). Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. New England Journal of Medicine, 387(1), 9-20.
[5] 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).
[6] 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.
[7] Li N, et al. A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer. Med. 2024;5(10):1255-1265.e2.