SKB BIO-B (06990) announced that its antibody-drug conjugate (ADC) A166 (also known as 博度曲妥珠單抗) has received approval from the National Medical Products Administration (NMPA) for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more previous anti-HER2 therapies. This approval is based on a multicenter, randomized, open-label Phase 3 study (KL166-III-06) designed to evaluate the efficacy and safety of A166 compared to trastuzumab emtansine (T-DM1) in HER2-positive patients with unresectable or metastatic breast cancer who had prior treatments with trastuzumab and taxanes. The pre-specified interim analysis showed that A166 significantly improved progression-free survival (PFS) compared to T-DM1, based on independent central review (BICR), with notable statistical and clinical significance. A beneficial trend in overall survival (OS) for A166 was also observed. The study results will be presented at the 2025 European Society for Medical Oncology (ESMO) conference in Berlin (abstract number: LBA24, preferred oral session 1 – metastatic breast cancer). The company has also initiated an open-label, multicenter Phase 2 clinical study of A166 for the treatment of HER2-positive unresectable or metastatic breast cancer previously treated with payloads of topoisomerase inhibitor ADCs. A166 is a differentiated HER2 ADC aimed at treating advanced HER2-positive solid tumors. Developed by the company, it couples a novel monomethyl auristatin F (MMAF) derivative (a highly cytotoxic microtubule inhibitor Duo-5) with the HER2 monoclonal antibody via a stable enzyme-cleavable linker, achieving a drug antibody ratio (DAR) of 2. A166 specifically binds to HER2 on tumor cell surfaces, leading to internalization by the tumor cells and subsequent release of the cytotoxic molecule Duo-5. Duo-5 induces tumor cell cycle arrest in the G2/M phase, resulting in apoptosis. After targeting HER2, A166 can also inhibit HER2-mediated signaling pathways and exhibits antibody-dependent cellular cytotoxicity (ADCC) activity.