Henlius' HLX22 with T-Dxd Begins Phase 2 Trial for HER2-low, HR-positive BC

Shanghai Henlius Biotech, Inc., based in Shanghai, China, has initiated a crucial phase 2 clinical trial for their innovative treatment targeting HER2-low, hormone receptor-positive breast cancer. The first patient in this trial, named HLX22-BC201, has now received treatment. This study combines the novel anti-HER2 monoclonal antibody (mAb), HLX22, with trastuzumab deruxtecan (T-DXd). The aim is to explore the potential of HLX22 in treating breast cancer, in addition to its earlier application in HER2-positive gastric cancer. This development represents a significant expansion in the therapeutic use of HLX22, potentially offering new hope for a broader range of cancer patients.

Breast cancer remains a major health issue worldwide, ranking as the second most common cancer, according to GLOBOCAN's 2022 report. The global incidence of breast cancer reached approximately 2.30 million new cases in 2022, with over 357,000 cases reported in China alone. Of these, a significant proportion can be classified as HER2-low breast cancers, a relatively new classification which includes tumors with IHC 1+ or 2+ and negative ISH results. This subclass represents nearly 45% to 55% of all breast cancer cases. Currently, targeted therapies for HER2-low, hormone receptor-positive breast cancer are limited, leaving patients to rely primarily on endocrine therapy or chemotherapy. Despite the introduction of T-DXd, which has shown promise in treating this type of cancer, there remains a pressing need for more effective and safer treatment options.

The novel antibody HLX22 works by binding to a specific site on the HER2 protein that is distinct from where trastuzumab binds. This unique binding ability allows HLX22 and trastuzumab to simultaneously attach to HER2 dimers on the tumor cell surface, thereby promoting the internalization and degradation of these dimers. Previous phase 2 trials combining HLX22 with HANQUYOU (a trastuzumab biosimilar) and chemotherapy showed significant improvements in survival rates and anti-tumor efficacy among patients with HER2-positive gastric and gastroesophageal junction cancer. These outcomes came with manageable safety profiles, suggesting the potential for broader applications of HLX22.

Building on these promising results, Henlius is broadening its research into HLX22's efficacy across various solid tumors. In 2024, the China National Medical Products Administration approved a phase 2 trial involving HLX22 combined with trastuzumab and chemotherapy, or with T-DXd, to treat HER2-expressing solid tumors. Preclinical studies demonstrated a synergistic anti-tumor effect and favorable safety when HLX22 was combined with T-DXd, indicating potential benefits for patients with HER2-expressing tumors. Henlius is committed to advancing the global development of HLX22, aiming to provide more affordable and effective treatment options worldwide.

HLX22-BC201 is a multicenter phase 2 study designed to assess the efficacy and safety of combining HLX22 with trastuzumab deruxtecan for patients with HER2-low, hormone receptor-positive advanced breast cancer who have not responded to standard therapy. Eligible patients will receive this combination therapy, with the primary endpoints being objective response rate and progression-free survival, as evaluated by an independent radiology review committee. Secondary endpoints will include overall survival, duration of response, safety, pharmacokinetics, immunogenicity, and biomarker analysis. This study represents a significant step forward in finding new therapies for breast cancer, addressing an urgent medical need.