Alphamab Oncology (stock code: 9966.HK) and CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (Stock Code: 1093.HK) jointly announced that anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 has been granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). The designation is for the treatment of platinum-resistant recurrent epithelial ovarian cancer (PROC), primary peritoneal cancer, or fallopian tube cancer, not restricted to HER2 expression levels.

Ovarian cancer (OC) ranks as the third most common gynecologic malignancy in China and continues to show a rising incidence, with the highest mortality rate among all malignant gynecologic tumors. The standard treatment regimens recommended by authoritative guidelines both domestically and internationally include surgery combined with platinum-based chemotherapy and targeted therapy maintenance. However, about 80% of OC cases recur, and eventually progress to platinum-resistant ovarian cancer (PROC), leaving patients with limited effective treatment options and poor prognosis. Non-platinum chemotherapy, with or without bevacizumab, is the standard treatment for PROC. Previous studies have shown that the objective response rate (ORR) of PROC treated with non-platinum chemotherapy is only 10% to 15%. The median progression-free survival (PFS) is only 3 to 4 months, and the median overall survival (OS) approximately 12 months, highlighting an urgent need for new treatment options.

The grant of Breakthrough Therapy Designation is based on the pooled analysis of two clinical studies, JSKN003-101 and JSKN003-102. JSKN003-101 (NCT05494918) is an open-label, multicenter, dose-escalation Phase I clinical study conducted in Australia, enrolling patients with advanced solid tumors expressing HER2 (IHC≥1+) or with HER2 mutations. JSKN003-102 (NCT05744427) is a Phase I/ II study conducted in China. The Phase I part enrolled patients with histologically confirmed HER2 expression (IHC≥1+) or HER2 mutations advanced solid tumors. The Phase II part enrolled patients with advanced solid tumors regardless of HER2 expression or mutation status. Pooled results have demonstrated that JSKN003 monotherapy has a favorable tolerability and safety profile, with promising efficacy signals in patients with advanced PROC, and the efficacy was observed across patients with (IHC 1+/2+3+) or without (IHC 0) HER2 expression, with or without prior bevacizumab and prior PARP inhibitor. Preliminary data from the pooled analysis of these two studies were presented at the 2024 European Society for Medical Oncology (ESMO) Congress.

The Phase III clinical study of JSKN003 for this indication is currently in the enrollment phase and the study is progressing smoothly. As a novel bispecific ADC, JSKN003 leverages the synergistic mechanism of enzyme catalysis and click chemistry to enhance serum stability and bystander effects, while demonstrating superior efficacy. The grant of Breakthrough Therapy Designation is expected to accelerate the clinical development, review and approval process of JSKN003, enabling more patients with PROC to benefit sooner.