Alphamab Oncology Doses First Patient in Phase III Trial of JSKN003 for HER2-Positive CRC

Alphamab Oncology announced on February 14, 2026, that the first patient was dosed in JSKN003-005, a Phase III study in HER2-positive advanced colorectal cancer. The investigational drug is JSKN003, described by the company as a biparatopic HER2 antibody-drug conjugate (ADC). JSKN003 is independently developed by the company and co-developed with JMT-Bio Technology Co., Ltd., a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd.

JSKN003-005 is a randomized, open-label, controlled, multicenter Phase III clinical study designed to evaluate the efficacy and safety of JSKN003 versus investigator's choice of regimen (regorafenib, fruquintinib, or trifluridine-tipiracil) in HER2-positive advanced CRC patients who have failed prior oxaliplatin, fluorouracil, and irinotecan therapy. The stated primary endpoint is progression-free survival (PFS) assessed by blinded independent central review (BICR) using RECIST v1.1. Secondary endpoints include OS, as well as investigator-assessed PFS and ORR, disease control rate (DCR), duration of response (DOR), time to response (TTR), and other endpoints evaluated by BICR/investigator according to RECIST v1.1.

According to data presented at the 2025 European Society for Medical Oncology (ESMO) Congress, JSKN003 demonstrated an objective response rate (ORR) of 68.8% and a median PFS of 11.04 months in 32 patients with HER2-positive advanced colorectal cancer.

Colorectal cancer is among the most common malignancies worldwide. China has a high incidence of CRC, with over 500,000 new cases diagnosed annually. Approximately 83% of patients are initially diagnosed at an advanced stage, and about 44% already have distant metastases to organs such as the liver or lungs. Despite advances in systemic therapies, the 5-year survival rate for patients with metastatic CRC remains below 20%, indicating a poor prognosis. 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.

JSKN003 is developed by site-specific conjugation to the Fc glycans of anbenitamab, resulting in a homogeneous and stable ADC with a DAR of 4. JSKN003 binds to two HER2 epitopes on tumor cells and releases topoisomerase I inhibitors through cellular endocytosis, exerting anti-tumor effects. Compared to similar ADCs, JSKN003 demonstrates better serum stability, reduced hematological toxicity, and stronger tumor inhibition and bystander effect, resulting in significantly wider therapeutic window.

Multiple registrational studies of JSKN003 are ongoing, including trials in HER2-positive breast cancer (BC), all-comer platinum-resistant ovarian cancer (PROC), HER2-low BC, and HER2-positive colorectal cancer (CRC).

JSKN003 has been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for gastric cancer (GC) and gastroesophageal junction cancer (GEJ), has been granted Fast Track Designation (FTD) by the FDA for the treatment of advanced or metastatic platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (PROC), not restricted by HER2 expression, and has been granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of patients with HER2-expressing PROC who have received prior treatment with bevacizumab. It has also been granted two BTDs by the National Medical Products Administration (NMPA) for PROC and HER2-positive advanced CRC that has failed prior oxaliplatin, fluorouracil, and irinotecan therapy.

In September 2024, the company entered a licensing agreement with JMT-Bio Technology Co., Ltd., a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. JMT-Bio was granted the exclusive license and sublicense rights to develop, sell, offer for sale and commercialize JSKN003, for tumor-related indications in mainland China (excluding Hong Kong, Macau or Taiwan). Alphamab retains exclusive production rights for JSKN003.