On October 17, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that the Company’s human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC) trastuzumab botidotin (also known as A166) was approved for marketing by the National Medical Products Administration (NMPA) for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer (BC) who have received one or more prior anti-HER2 therapy.

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The approval is based on a multi-center, randomized, open-label, controlled, Phase 3 KL166-III-06 study that evaluates the efficacy and safety profile of trastuzumab botidotin versus T-DM1 in patients with HER2-positive unresectable or metastatic BC who have received prior trastuzumab and taxane-containing regimens. At a pre-specified interim analysis, trastuzumab botidotin monotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) as assessed by the blinded independent central review (BICR) compared with T-DM1; the beneficial trend for overall survival (OS) of trastuzumab botidotin was also observed. Results from this study will be presented as an oral report at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress held in Berlin, Germany (Presentation # LBA24, Proffered paper session 1: Breast cancer, metastatic).

The Company has initiated an open, multi-center Phase 2 clinical study of trastuzumab botidotin in the treatment of HER2+ unresectable or metastatic BC that previously received a topoisomerase inhibitor ADC.

Dr. Michael Ge, CEO of Kelun-Biotech said, "We are thrilled to see our first HER2 ADC drug, trastuzumab botidotin, successfully approved for market. This marks a significant advancement in the treatment of HER2-positive breast cancer. As China’s first domestically developed HER2 ADC capable of broadly covering 2L+ HER2 BC patients, trastuzumab botidotin leverages its differentiated structural design to deliver superior efficacy while addressing unmet clinical needs in this population."

About HER2+ BC

Breast cancer, as the most common malignant tumor, poses a serious threat to women’s health. Among its subtypes, HER2-positive breast cancer accounts for approximately 15%–20% of all breast cancer cases[1], and is characterized by its aggressiveness and high malignancy. According to the 2025 CSCO guidelines, first-line treatment for HER2-positive breast cancer primarily consists of trastuzumab and pertuzumab in combination with taxane-based chemotherapeutic agents. Second-line treatment regimens comprise tyrosine kinase inhibitors (TKIs, such as pyrotinib) and antibody-drug conjugates (ADCs, such as T-DM1 and T-DXd). Following disease progression on second-line therapy, subsequent treatment strategies are determined based on prior second-line regimens, the patient’s tolerance to therapy, tumor burden, and other relevant factors. Despite recent advances in anti-HER2 therapeutics, a significant number of patients still experience drug resistance or severe adverse effects, highlighting an urgent need for agents with improved safety profiles to address the treatment requirements of patients with recurrent or drug-resistant HER2-positive breast cancer.

A bout trastuzumab botidotin

Trastuzumab botidotin is a differentiated HER2 ADC to treat advanced HER2+ solid tumors. As an innovative HER2 ADC developed by the Company, it conjugates a novel, monomethyl auristatin F (MMAF) derivative (a highly cytotoxic tubulin inhibitor, Duo-5) via a stable, enzyme-cleavable linker to a HER2 monoclonal antibody with a drug-to-antibody-ratio (DAR) of 2. Trastuzumab botidotin specifically binds to HER2 on the surface of tumor cells and is internalized by tumor cells, releasing the toxin molecule Duo-5 inside the cell. Duo-5 induces tumor cell cycle arrest in the G2/M phase, leading to tumor cell apoptosis. After targeting HER2, trastuzumab botidotin can also inhibit the HER2 signaling pathway; it has antibody-dependent cell-mediated cytotoxicity (ADCC) activity.

(Press release, Kelun, OCT 17, 2025, View Source [SID1234656754])