ACE-Breast-02: a randomized phase III trial of ARX788 versus lapatinib plus capecitabine for HER2-positive advanced breast cancer

This phase III trial aimed to compare ARX788, a site-specific, construct-homogeneous antibody-drug conjugate, with lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) who had progressed on one line of trastuzumab based regimen. Eligible patients were randomized (1:1) to receive ARX788 (1.5 mg/kg, IV, Q3W) or lapatinib plus capecitabine (LC: lapatinib 1250 mg QD; capecitabine 1000 mg/m<sup>2</sup> BID, days 1-14, Q3W) and stratified by prior chemotherapy lines (0-1 versus >1) and visceral metastasis (yes versus no). The primary outcome was progression-free survival (PFS) assessed by a blinded independent central review (BICR). A total of 441 patients were randomly assigned to receive either ARX788 (n = 221) or LC (n = 220). The median PFS was 11.3 (95% confidence interval [CI], 8.4-13.8) months with ARX788 compared with 8.2 (95% CI, 6.9-8.7) months with LC, as per BICR (hazard ratio [HR] 0.64, p = 0.0006). Frequencies of treatment-related adverse events (TRAEs) of any grade were 98.6% and 99.1% for ARX788 and LC, respectively. Grade ≥3 TRAEs were 41.4% and 40.0%, respectively, the most common adverse events were blurred vision (12.3%), dry eye (9.1%), keratopathy (5.9%), and interstitial lung disease (ILD, 5.9%) with ARX788; hand-foot syndrome (18.1%) and hypokalemia (5.1%) with LC; all the hematological and gastrointestinal events of grade ≥3 with ARX788 were less than 3%. Six treatment-related deaths occurred, with three cases possibly related to ILD. ARX788 significantly improved PFS compared with LC in patients with HER2-positive ABC with a distinct toxicity profile, supporting it as a potential treatment option.

Authors

Institutions

Publication Details

Journal
Signal Transduction and Targeted Therapy
Published
2025-02-16
DOI
https://doi.org/10.1038/s41392-025-02149-3
Citations
24
Primary Topic
HER2/EGFR in Cancer Research
Type
article
Field-Weighted Citation Impact
25.09
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

ACE-Breast-02: a randomized phase III trial of ARX788 versus lapatinib plus capecitabine for HER2-positive advanced breast cancer

Zhongsheng Tong, Jingfen Wang, Leiping Wang, Feilin Cao et al.
24 citations
Signal Transduction and Targeted Therapy
HER2/EGFR in Cancer Research
25.09
article

ACE-Breast-02: a randomized phase III trial of ARX788 versus lapatinib plus capecitabine for HER2-positive advanced breast cancer

Zhongsheng Tong, Jingfen Wang, Leiping Wang, Feilin Cao, Ping Lu, Weimin Xie, Xinshuai Wang, Min Yan, Xiaojia Wang, Zhendong Chen, Tao Sun, Xichun Hu, Aimin Zang, Lilin Chen, Ruiwen Zhang, Jian Zhang, Haixia Wang, Wei Li, Shusen Wang, Qingyuan Zhang, Xiuqing Nie, Sanyuan Sun, Yingying Du, Jinsheng Wu, Lei Yuan, Yongqiang Zhang, Wei Liu, Faliang Xu, Quchang Ouyang, Ying Wang
article en
24 citations

Abstract

This phase III trial aimed to compare ARX788, a site-specific, construct-homogeneous antibody-drug conjugate, with lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) who had progressed on one line of trastuzumab based regimen. Eligible patients were randomized (1:1) to receive ARX788 (1.5 mg/kg, IV, Q3W) or lapatinib plus capecitabine (LC: lapatinib 1250 mg QD; capecitabine 1000 mg/m<sup>2</sup> BID, days 1-14, Q3W) and stratified by prior chemotherapy lines (0-1 versus >1) and visceral metastasis (yes versus no). The primary outcome was progression-free survival (PFS) assessed by a blinded independent central review (BICR). A total of 441 patients were randomly assigned to receive either ARX788 (n = 221) or LC (n = 220). The median PFS was 11.3 (95% confidence interval [CI], 8.4-13.8) months with ARX788 compared with 8.2 (95% CI, 6.9-8.7) months with LC, as per BICR (hazard ratio [HR] 0.64, p = 0.0006). Frequencies of treatment-related adverse events (TRAEs) of any grade were 98.6% and 99.1% for ARX788 and LC, respectively. Grade ≥3 TRAEs were 41.4% and 40.0%, respectively, the most common adverse events were blurred vision (12.3%), dry eye (9.1%), keratopathy (5.9%), and interstitial lung disease (ILD, 5.9%) with ARX788; hand-foot syndrome (18.1%) and hypokalemia (5.1%) with LC; all the hematological and gastrointestinal events of grade ≥3 with ARX788 were less than 3%. Six treatment-related deaths occurred, with three cases possibly related to ILD. ARX788 significantly improved PFS compared with LC in patients with HER2-positive ABC with a distinct toxicity profile, supporting it as a potential treatment option.

Signal Transduction and Targeted TherapyVol. 10(1)
Xinjiang Medical University (CN), Harbin Medical University (CN), Sun Yat-sen University (CN), Chongqing University (CN), Shaoxing University (CN), Jilin University (CN), Anhui Medical University (CN), Wenzhou Medical University (CN), Tianjin Medical University Cancer Institute and Hospital (CN), Zhengzhou University (CN), First Affiliated Hospital of Xiamen University (CN), Xian Central Hospital (CN), Fudan University Shanghai Cancer Center (CN), Sun Yat-sen Memorial Hospital (CN), Zhejiang Cancer Hospital (CN), Tumor Hospital of Xinjiang Medical University (CN), Third Affiliated Hospital of Harbin Medical University (CN), Hunan Cancer Hospital (CN), Beijing Hospital (CN), First Hospital of Jilin University (CN), Hainan General Hospital (CN), Xuzhou Central Hospital (CN), First Affiliated Hospital of Henan University of Science and Technology (CN), First Affiliated Hospital of Anhui Medical University (CN), Affiliated Hospital of Hebei University (CN), Henan Cancer Hospital (CN), Sun Yat-sen University Cancer Center (CN), Second Affiliated Hospital of Anhui Medical University (CN), Chongqing Cancer Hospital (CN), Tumor Hospital of Guangxi Medical University (CN), Liaoning Cancer Hospital & Institute (CN), Hainan Medical University (CN), Henan Medical University (CN), China Medical University (CN)
Good health and well-being
Openalex Percentile: Top 0%
HER2/EGFR in Cancer Research
25.09
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.