Neoadjuvant Anbenitamab and HB1801 in ERBB2 -Positive Breast Cancer
Abstract
IMPORTANCE The combination of neoadjuvant taxanes with trastuzumab and pertuzumab remains the cornerstone treatment strategy in ERBB2 -positive breast cancer. Anbenitamab (a ERBB2 -biparatopic antibody that induces profound receptor clustering) and HB1801 (a solvent-free albumin-bound docetaxel), have shown promising antitumor activity and an acceptable safety profile in patients with breast cancer. OBJECTIVE To evaluate whether neoadjuvant anbenitamab combined with HB1801 could improve efficacy without increasing toxic effects for patients with early ERBB2 -positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS This multicenter, phase 3 registrational randomized clinical trial enrolled patients with stage II or III ERBB2 -positive breast cancer from 61 hospitals in China between December 19, 2024, and August 29, 2025 (data cutoff: January 28, 2026). Data were analyzed from February 1 to March 20, 2026. INTERVENTIONS Patients were randomly assigned (1:1) to receive 6 cycles of neoadjuvant anbenitamab plus HB1801, with or without carboplatin (investigational group), or trastuzumab, pertuzumab, and docetaxel, with or without carboplatin (control group). MAIN OUTCOMES AND MEASURES The primary end point was total pathological complete response (tpCR) assessed by a blinded independent review committee. RESULTS Among 521 included patients (median [IQR] age, 52.0 [23-79] years), 263 were randomized to the investigational group and 258 to the control group. The tpCR rate was significantly higher in the investigational group than the control group (164 patients [62.4%] vs 132 patients [51.2%]; absolute difference, 11.4 [95% CI, 3.2 to 19.6] percentage points; P = .004). Benefit was consistent across subgroups, including subgroups with hormone receptor–positive disease (77 patients [51.7%] vs 63 patients [44.4%]), hormone receptor–negative disease (87 patients [76.3%] vs 69 patients [59.5%]), early-stage disease (111 patients [63.8%] vs 87 patients [51.8%]), locally advanced disease (53 patients [59.6%] vs 45 patients [50.0%]), with carboplatin treatment (74 patients [66.7%] vs 61 patients [54.5%]), and without carboplatin treatment (90 patients [59.2%] vs 71 patients [48.6%]). Grade 3 or 4 treatment-related adverse events occurred in 77 patients (29.3%) in the investigational group and 73 patients (28.3%) of the control group. No treatment-related deaths occurred. CONCLUSIONS AND RELEVANCE This randomized clinical trial found that neoadjuvant anbenitamab and HB1801 in patients with breast cancer significantly improved the tpCR rate compared with standard therapy with a highly manageable safety profile. This new combination may offer an improved treatment option, although long-term survival follow-up analyses are warranted. Trial Registration ClinicalTrials.gov Identifier: NCT06747338
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Authors: Junjie Li, Tong Liu, Ke-Da Yu, Huawei Yang, Zhen Huang, Yi Zeng, Peng Ji, Xiaoke Hou, Chunping Liu, Yiwen Zhang, Nanlin Li, Zhong Ouyang, Xiaobo Wu, Xiaorong Bai, Yanxiang Guo, Guohui Han, Shien Cui, Zhijun Zhu, Yu Zhang, Xiaobo Hu, Xiaopeng Ma, Peifen Fu, Jinhai Zhu, Yuan Dong, Tao Wu, Hongyan Jia, Fei Xu, Yu Ren, Jianyun Nie, Bing Dai, Qiang Mu, Tao Sun, Jing Luo, Zhenchuan Song, Xiangshun Kong, Hao Zhang, Zhiyong Wu, Zhihong Wang, Dong Song, Haiquan Jia, Tao Wei, Pingming Fan, Fan Yao, Ru Chen, Guie Lai, Xin Zhou, Taolang Li, Chao Deng, Xuemei Jiang, Xiaochun Wang, Jingfen Wang, Dun Xiong, Shuqun Zhang, Hongwei Yang, Yongzhong Yao, Guobing Yin, Guangyu Yao, Li Zhou, Shu Wang, Zhigang Yu, Yang Yu, Ye Lv, Hesheng Qian, Huiping Li, Wenhui Guo, Wei Huang, Silong Xiang, Kai Zou, Hang He, Lei Fan, Zhi-Ming Shao, BCTOP study group
Institutions: First Affiliated Hospital Zhejiang University, Bengbu Medical College, First Affiliated Hospital of Bengbu Medical College, Hebei Medical University, Peking University, Qingdao University, Zhongshan Hospital, Affiliated Hospital of Hebei University, Sun Yat-sen University, Zunyi Medical University, Dalian Medical University, Fourth Hospital of Hebei Medical University, Kunming Medical University, Chongqing Medical University, Fujian Medical University, Hainan General Hospital, First Affiliated Hospital of Kunming Medical University, Southern Medical University, Union Hospital, Harbin Medical University, Guiyang Medical University, Affiliated Hospital of Guizhou Medical University, First Affiliated Hospital of Xiamen University, Second Affiliated Hospital of Chongqing Medical University, Sun Yat-sen University Cancer Center, Shanxi Medical University, Deyang Stomatological Hospital, Xijing Hospital, Guangxi Medical University, China Medical University, Jilin University, Peking University People's Hospital, Shanghai Medical College of Fudan University, Zhejiang Cancer Hospital, Wuhan Union Hospital, Nanjing Drum Tower Hospital, Hainan Medical University, Third Affiliated Hospital of Harbin Medical University, Puer University, Fudan University Shanghai Cancer Center, Sichuan Mianyang 404 Hospital, Yuncheng University, Xingtai People's Hospital, Second Hospital of Shandong University, Jinzhou Medical University, Ningxia Medical University, Ningxia Medical University General Hospital, Suizhou Central Hospital, First Hospital of Shanxi Medical University, Peking University Cancer Hospital, Nanyang Institute of Technology, Guizhou Cancer Hospital, Hunan Cancer Hospital, Chongqing Cancer Hospital, Tumor Hospital of Guangxi Medical University, Fuyang Second People's Hospital, The First People's Hospital of Changde, First Affiliated Hospital of Gannan Medical University, Anhui Provincial Hospital, Chizhou University, Shanxi Provincial Cancer Hospital, Second Affiliated Hospital of Xi'an Jiaotong University, Fujian Provincial Cancer Hospital, Liaoning Cancer Hospital & Institute, Zhongshan People's Hospital, First Affiliated Hospital of Xi'an Jiaotong University, Qingdao Municipal Hospital, First Hospital of Jilin University, Linyi People's Hospital, Shanghai Institute of Pharmaceutical Industry, Shantou Central Hospital, Third People 's Hospital of Chongqing, Jiangmen Central Hospital, Sichuan Provincial Hospital of Traditional Chinese Medicine, Anyang Tumor Hospital, Haikou City People's Hospital, Hainan Provincial Hospital of Traditional Chinese Medicine, Yulin University, The Central Hospital of Shaoyang, Fuyang Maternity and Child Health Care Hospital