Alphamab Oncology announced that the first patient has been dosed in a phase III clinical study (JSKN016-301) evaluating JSKN016, a novel TROP2/HER3 bispecific antibody-drug conjugate (ADC) for the treatment of triple-negative breast cancer (TNBC). This milestone brings another innovative bispecific ADC from the company's pipeline into pivotal development, reinforcing its potential to offer a more effective and safer treatment option for patients with TNBC.

Breast cancer is the most commonly diagnosed malignancy among women worldwide, with a growing disease burden. TNBC accounts for approximately 15–20% of all breast cancer cases and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. This subtype is associated with high invasiveness, increased recurrence rates, and poor prognosis. For patients with locally advanced or metastatic TNBC who have progressed after at least one line of systemic chemotherapy (particularly taxane-based therapy), subsequent treatment options remain limited. Current therapies typically yield objective response rates (ORR) of only 10–20% and median progression-free survival (mPFS) of approximately one to three months, underscoring a significant unmet medical need.

JSKN016 is a bispecific ADC developed by Alphamab Oncology leveraging its proprietary single-domain antibody and bispecific antibody platforms. Designed to co-target TROP2 and HER3, JSKN016 features a homogeneous DAR4 ADC achieved through glycan-specific conjugation. This enables simultaneous blockade of tumor signaling pathways and enhanced intracellular delivery of a topoisomerase I inhibitor for precise and potent antitumor activity. Early-phase clinical studies have demonstrated encouraging antitumor activity and a favorable safety profile of JSKN016 in heavily pretreated advanced TNBC and other solid tumors.

JSKN016-301 is an open-label, randomized, controlled, multicenter phase III trial expected to be conducted at approximately 60 sites across China. The study aims to evaluate the efficacy and safety of JSKN016 versus treatment of physician's choice (TPC) in patients with unresectable locally advanced, recurrent, or metastatic TNBC who have failed at least two lines of systemic therapy. Primary endpoints are progression-free survival (PFS) and overall survival (OS) as assessed by a Blinded Independent Review Committee (BIRC) per RECIST v1.1. Secondary endpoints include investigator-assessed PFS, ORR, disease control rate (DCR), and duration of response (DoR), as well as BIRC-assessed ORR, DCR, and DoR.