ALPHAMAB-B(09966): The phase III clinical study of JSKN016 for the treatment of TNBC has completed the first patient dosing.

ALPHAMAB-B (09966) announced that a Phase III clinical study (study code: JSKN016-301) of a bispecific antibody-drug conjugate (ADC) targeting the tumor-associated antigens TROP2 and HER3 for the treatment of triple-negative breast cancer (TNBC) has successfully completed dosing in its first patient. This milestone marks the entry of another innovative bispecific ADC developed by the company into a crucial clinical development stage, offering a potentially more effective and safer ADC treatment option for the target patient population. Breast cancer (BC) is the most common malignant tumor among women worldwide, with increasing incidence and mortality rates. TNBC accounts for approximately 15-20% of all BC cases. Due to the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), this subtype of tumor is often highly aggressive, with a high recurrence rate and poor prognosis. For patients with locally advanced or metastatic TNBC who have failed at least one line of systemic therapy (especially taxanes), subsequent treatment options remain limited. The objective response rate (ORR) of existing therapies is usually only about 10-20%, with a median progression-free survival (PFS) of 1 to 3 months, highlighting the need for more effective treatment strategies. JSKN016-301 is an open-label, randomized, controlled, multicenter Phase III clinical study expected to be conducted at approximately 60 clinical research centers in China. The study plans to enroll patients with locally advanced, recurrent, or metastatic TNBC who are ineligible for surgical resection and have failed at least second-line systemic therapy. The study will compare JSKN016 with the investigator's choice of treatment, with the primary endpoints being PFS and overall survival (OS) assessed by the blinded independent radiographic assessment committee (BIRC) according to RECIST v1.1 criteria, and secondary endpoints including investigator-assessed PFS, ORR, disease control rate (DCR), duration of response (DoR), as well as BIRC-assessed ORR, DCR, and DoR. JSKN016 is a proprietary bispecific ADC designed to simultaneously target TROP2 and HER3 on tumor cells. It is based on the company's unique glycoengineering platform. After binding to TROP2 or HER3 on the surface of tumor cells, JSKN016 enters the lysosomes through targeted endocytosis and releases a topoisomerase I inhibitor with cytotoxicity, inducing tumor cell death. Additionally, the inhibitor can penetrate the cell membrane to exert bystander effects on antigen-negative tumor cells. The combined action of both can effectively inhibit tumor cell growth. JSKN016 has demonstrated good anti-tumor activity and safety in various solid tumors. Clinical studies evaluating the use of JSKN016 as a monotherapy and in combination therapies for lung cancer and BC are currently underway, with a Phase III clinical study for TNBC in progress.