Alphamab Oncology's JSKN003 Receives Breakthrough Therapy Designation for Advanced Colorectal Cancer

Alphamab Oncology and CSPC Pharmaceutical Group Co., Ltd. jointly announced that biparatopic HER2-targeting ADC JSKN003 has been granted another breakthrough therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of HER2-positive advanced colorectal cancer (CRC) in patients who have failed prior treatments with oxaliplatin, fluorouracil and irinotecan. This latest designation in colorectal cancer further underscores the clinical value and global development potential of JSKN003 across multiple refractory tumor types.

Key Takeaways:

• JSKN003 has received breakthrough therapy designations from the CDE for platinum-resistant ovarian cancer (PROC) and HER2-positive advanced colorectal cancer (CRC) that has failed prior treatments with oxaliplatin, fluorouracil, and irinotecan.
• JSKN003 is currently being evaluated in multiple Phase II and Phase III clinical studies in China for the treatment of various solid tumors, including breast cancer, ovarian cancer, and gastric cancer.
• A total of 33 patients with HER2-positive advanced metastatic CRC received JSKN003 monotherapy in a phase I (dose escalation and expansion) and phase II (cohort expansion) clinical study in China, with 42.4% of patients having previously received 3 or more prior lines of antitumor therapy.
• Among 32 efficacy-evaluable patients, the overall response rate (ORR) was 68.8%, the disease control rate (DCR) was 96.9%, and the median duration of response (DoR) was 9.89 months.
• JSKN003 is a biparatopic HER2-targeting antibody-drug conjugate (ADC) that Bind to two HER2 epitopes on tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, exerting anti-tumor effects.
• JSKN003 has a better serum stability, reduced hematological toxicity, and stronger tumor inhibition and bystander effect, resulting in a wider therapeutic window compared to similar ADCs.
• The median follow-up time was 9.26 months, and 7 patients experienced Grade 3 or above treatment-related adverse events (TRAEs).

Statistics:

• Approximately 1.93 million newly diagnosed cases and 903,900 deaths were attributed to CRC globally in 2022, ranking third in incidence and second in mortality among all cancers. (IARC)
• Over 500,000 new cases of CRC are reported annually in China, with a continuing upward trend.
• The median progression-free survival (mPFS) of approved therapies for patients with HER2-positive advanced CRC who have failed prior treatments with oxaliplatin, fluorouracil, and irinotecan is only 2.0 to 3.7 months.
• The median overall survival (mOS) is approximately 7 to 10 months.

Sources:

• Alphamab Oncology, October 20, 2023: Press Release
• International Agency for Research on Cancer (IARC), 2022: Cancer Globally, Colorectal Cancer
• European Society for Medical Oncology Congress 2025: Presentation, JSKN003-102, NCT05744427
• U.S. Food and Drug Administration (FDA): Orphan Drug Designation, JSKN003 for Gastric and Gastroesophageal Junction Cancer