Alphamab Oncology (stock code: 9966.HK) and CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (Stock Code: 1093.HK) jointly announced that biparatopic HER2-targeting antibody-drug conjugate (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 indication of monotherapy for the treatment of HER2-positive advanced colorectal cancer (CRC) in patients who have failed prior treatments with oxaliplatin, fluorouracil and irinotecan. Previously, JSKN003 had received breakthrough therapy designation from the CDE for platinum-resistant ovarian cancer (PROC) (not restricted by HER2 expression), as well as clinical trial approval from the U.S. Food and Drug Administration (FDA). It has also been granted Orphan Drug Designation by the U.S. FDA for gastric and gastroesophageal junction cancer. This latest designation in colorectal cancer further underscores its clinical value and global development potential across multiple refractory tumor types.

Colorectal cancer is among the most common malignancies worldwide. According to data from the International Agency for Research on Cancer (IARC), there were approximately 1.93 million newly diagnosed cases and about 903,900 deaths attributed to CRC globally in 2022, ranking third in incidence and second in mortality among all cancers. In China, CRC has the second-highest incidence after lung cancer, with over 500,000 new cases annually and a continuing upward trend. There are currently no HER2-targeted therapies approved in China for CRC. For patients with HER2-positive advanced CRC who have failed prior treatments with oxaliplatin, fluorouracil and irinotecan, the median progression-free survival (mPFS) of approved therapies is only 2.0 to 3.7 months, and the median overall survival (mOS) is approximately 7 to 10 months. There remains a significant unmet clinical need within this patient population.

Clinical studies demonstrated that JSKN003 monotherapy exhibited notable efficacy and a favorable safety profile in patients with HER2-positive advanced CRC, showing meaningful clinical advantages over existing therapeutic options. As of June 30, 2025, a total of 33 patients with HER2-positive advanced metastatic CRC, were enrolled and received JSKN003 monotherapy in a phase I (dose escalation and expansion) and phase II (cohort expansion) clinical study in China (JSKN003-102, NCT05744427), with 42.4% of these 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%. Additionally, among 31 BRAF V600E wild-type patients, the ORR was 71.0%, the DCR was 100%, and median duration of response (DoR) was 9.89 months, the median PFS achieved 11.04 months, with a 9-month PFS rate of 66.6%. In terms of safety, the median follow-up time was 9.26 months. 7 patients experienced Grade 3 or above treatment-related adverse events (TRAEs). There were no TRAEs led to discontinuation or death. Detailed data from the study were presented recently at the 2025 European Society for Medical Oncology Congress (ESMO Congress 2025). By comparison, in a similar patient population, trastuzumab deruxtecan (DS-8201) previously reported an ORR of 37.8%, a PFS of 5.8 months, and Grade 3 or above adverse events in nearly 50% of patients.

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. This latest breakthrough therapy designation for JSKN003 is expected to further accelerate its development and review processes, with the aim of bringing benefits to more cancer patients sooner.