Results from Phase III Study of Trastuzumab Botidotin versus T-DM1 in HER2-Positive Breast Cancer Published in JCO

CHENGDU, China, Sept. 14, 2026 /PRNewswire/ -- Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. ("Kelun-Biotech" or "the Company", 6990.HK) announced that results from the phase III registrational study of its novel human epidermal growth factor receptor 2 (HER2)-targeted antibody–drug conjugate (ADC) trastuzumab botidotin (舒泰莱^®) in HER2-positive unresectable or metastatic breast cancer (BC) have been published in Journal of Clinical Oncology (JCO, impact factor (IF)=44.7). Professor Xichun Hu and Professor Hongxia Wang of Fudan University Shanghai Cancer Center, and Dr. Junyou Ge, Director of the National Engineering Research Center of Targeted Biologics act as the co-senior authors. Professor Jian Zhang of Fudan University Shanghai Cancer Center, Professor Quchang Ouyang of Hunan Cancer Hospital, Professor Qingyuan Zhang of Harbin Medical University Cancer Hospital, Professor Huihui Li of Cancer Hospital of Shandong First Medical University, and Professor Xu Wang of Tianjin Medical University Cancer Institute and Hospital act as the co-first authors. These findings had previously been selected as a Late-Breaking Abstract (LBA) and presented as an oral presentation at the 2025 European Society for Medical Oncology (ESMO) Congress.

This randomized, open-label, multicenter phase III study was designed to evaluate the efficacy and safety of trastuzumab botidotin monotherapy versus trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable or metastatic BC who had received prior trastuzumab and taxane-containing regimens. A total of 365 patients were randomized 1:1 to receive trastuzumab botidotin or T-DM1. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR), and secondary endpoints included overall survival (OS), objective response rate (ORR), and duration of response (DoR).

As of the data cutoff date of April 26, 2025, with a median follow-up of 14.9 months, efficacy results showed:

• Median PFS was significantly prolonged in the trastuzumab botidotin group compared with the T-DM1 group (11.1 months vs. 4.4 months; hazard ratio (HR) = 0.39) (Figure A), meeting the primary endpoint of the study; consistent PFS benefit was observed across all prespecified subgroups (Figure B).
   
•  Trastuzumab botidotin group demonstrated deeper and more durable tumor responses compared with T-DM1 group, with an ORR of 76.9% vs. 53.0% and a median DoR of 12.2 months vs. 5.7 months (Figure C).
  
  
•  OS data were not mature in both groups, but an OS benefit trend was observed in trastuzumab botidotin group, demonstrating a 38% reduction in the risk of death (Figure D).

In terms of safety, patients in the trastuzumab botidotin group had a low incidence of interstitial lung disease (ILD), and the incidences of hematologic, hepatic, and gastrointestinal toxicities were notably lower than those in the T-DM1 group, along with lower rates of serious adverse events (SAEs) and treatment discontinuations. The most common treatment-related adverse events (TRAEs) in trastuzumab botidotin group were ocular events, which could be recovered or reversed after management with standardized strategies.

The publication of the phase III results for trastuzumab botidotin in Journal of Clinical Oncology marks a major international academic breakthrough for a domestically developed HER2 ADC backed by high-level clinical evidence. This is the first phase III trial in China for a HER2 ADC compared head-to-head with T-DM1 with positive results. The data showed that trastuzumab botidotin demonstrated improvements in key efficacy endpoints including PFS, ORR, and DoR, along with a favorable safety profile. Based on these positive results, trastuzumab botidotin has been approved by China's National Medical Products Administration (NMPA) for the treatment of second-line or later HER2-positive BC, becoming the first domestically developed HER2 ADC approved for this indication in China and providing a new treatment option for patients with HER2-positive advanced breast cancer.

About Trastuzumab botidotin(舒泰莱^®)

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 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.

Based on the results of a multi-center, randomized, open-label, controlled Phase 3 KL166-III-06 study, trastuzumab botidotin was approved for marketing by the NMPA for adult patients with unresectable or metastatic HER2 positive BC who have received one or more prior anti-HER2 therapy. At a pre-specified interim analysis, trastuzumab botidotin monotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of PFS as assessed by the BICR compared with T-DM1; the beneficial trend for OS of trastuzumab botidotin was also observed.

Currently, 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 payload ADC.

About Kelun-Biotech

Kelun-Biotech (6990.HK) is a holding subsidiary of Kelun Pharmaceutical, which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. Kelun-Biotech focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. Kelun-Biotech is committed to becoming a leading global enterprise in the field of innovative drugs. At present, Kelun-Biotech has more than 30 ongoing key innovative drug projects, of which 4 projects with 8 indications have been approved for marketing, 2 projects with 3 indications are in the NDA stage and more than 10 projects are in the clinical stage. Kelun-Biotech has established one of the world's leading proprietary ADC and novel DC platforms, OptiDC™, and has 2 ADC projects with 5 indications approved for marketing, and multiple ADC and novel DC assets in clinical or preclinical research stage. For more information, please visit https://en.kelun-biotech.com/. 

SOURCE Kelun-Biotech