CSPC Pharmaceutical Group announced that JSKN003, an antibody-drug conjugate targeting HER2 dual epitopes, has received its second Breakthrough Therapy Designation from China's National Medical Products Administration (NMPA). The designation covers monotherapy treatment for patients with HER2-positive advanced colorectal cancer who have failed prior treatment with oxaliplatin, fluorouracil, and irinotecan.
The drug is co-developed by Shanghai Jimantite Biotechnology Co., Ltd., a CSPC Pharma subsidiary, and Corning Jie Rui BioPharmaceutical Co., Ltd. This marks the second breakthrough designation for JSKN003, following its March 2025 approval for platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
Addressing Critical Unmet Medical Need
Colorectal cancer represents a significant global health burden, with 1.9262 million new cases worldwide in 2022 and 903,900 deaths, according to International Agency for Research on Cancer statistics. The disease ranks third in incidence and second in mortality among all malignant tumors globally. In China, colorectal cancer is particularly prevalent, ranking second in incidence after lung cancer with over 500,000 new cases annually.
For patients with HER2-positive advanced colorectal cancer who have exhausted standard treatment options, current approved therapies in China include regorafenib, fruquintinib, and trifluridine/tipiracil. However, these treatments offer limited efficacy, providing median progression-free survival of only 2-3.7 months and median overall survival of approximately 7-10 months.
Promising Clinical Results
At the 2025 American Society of Clinical Oncology Annual Meeting, researchers presented a pooled analysis of JSKN003 monotherapy in patients with advanced HER2 high-expression gastrointestinal tumors. The analysis combined data from a Phase I study conducted in Australia (JSKN003-101) and a Phase I/II study conducted in China (JSKN003-102).
As of February 28, 2025, the studies enrolled 50 patients with advanced gastrointestinal tumors with high HER2 expression, including 23 colorectal cancer patients. Notably, 38% of participants had received three or more prior lines of anti-tumor therapy, representing a heavily pretreated population.
Among 21 evaluable colorectal cancer patients who underwent at least one tumor response assessment, JSKN003 demonstrated substantial efficacy. The objective response rate reached 61.9%, with a disease control rate of 95.2%. The median progression-free survival extended to 13.77 months, while the median duration of response was 12.06 months. In the subset of 20 colorectal cancer patients with BRAFV600E wild-type tumors, the objective response rate reached 65.0%.
Favorable Safety Profile
Safety analysis of 43 patients treated at the recommended Phase II dose revealed a manageable adverse event profile. Only six patients (14.0%) experienced treatment-related adverse events of Grade 3 or higher, while three patients (7.0%) had treatment-related serious adverse events. Seven patients (16.3%) required dose reductions due to treatment-related adverse events. Importantly, no treatment-related adverse events led to treatment discontinuation or death.
Accelerated Development Timeline
The Breakthrough Therapy Designation is expected to expedite JSKN003's development and regulatory review process. Multiple Phase II and III clinical trials are currently underway in China, evaluating JSKN003 for treating various solid tumors including breast cancer, ovarian cancer, and gastric cancer.
The designation underscores JSKN003's potential to address significant clinical advantages compared to existing treatments for this challenging patient population, offering hope for improved outcomes in HER2-positive advanced colorectal cancer.
