Alphamab Oncology and CSPC Pharmaceutical Group Co., Ltd.  jointly announced that anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 has received approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) to initiate a Phase III clinical study (Study ID: JSKN003-301). The study aims to compare the efficacy and safety of JSKN003 versus trastuzumab emtansine (T-DM1) for the treatment of HER2-positive advanced breast cancer. This marks the third Phase III clinical study initiated for JSKN003, following the trials in HER2 low-expressing breast cancer and platinum-resistant ovarian cancer.

Breast cancer is one of the most common malignant tumors among women worldwide and the most prevalent cancer in women in China. HER2-positive breast cancer accounts for 20% to 25% of all breast cancer cases in China, and it is the most aggressive and highly malignant subtype, prone to recurrence, metastasis, and worse prognosis. In recent years, targeted therapies and combination treatments have emerged and significantly improved the diagnosis and treatment of HER2-positive breast cancer. However, recurrent and metastatic breast cancer still poses a severe threat to patients' health, with a significant unmet clinical need.

JSKN003 is an anti-HER2 bispecific ADC developed inhouse with Alphamab's proprietary Glycan-specific conjugation platform. The antibody molecule KN026 is site-specifically modified via enzyme catalytic reaction and click chemistry to achieve a drug-to-antibody ratio (DAR) of approximately 4. It can bind HER2 on the surface of tumor cells, and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exert anti-tumor effects. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window. Multiple clinical studies at various stages of JSKN003 conducted in China and Australia have demonstrated favorable tolerability and safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with advanced solid tumors, especially in patients with HER2-expressing breast cancer, platinum-resistant ovarian cancer (PROC), or high HER2-expressing solid tumors.

JSKN003-301 is a randomized, controlled, open-label, multicenter, Phase III clinical study aimed at evaluating the efficacy and safety of JSKN003 compared to emtansine (T-DM1) in the treatment of patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who have previously received trastuzumab or taxane-based therapies. The primary endpoint of the study is progression-free survival (PFS) as assessed by the Blinded Independent Review Committee (BIRC).