Abstract PS10-57: A randomized, multicenter, open-label phase II/III study of ARX788 vs Lapatinib and Capecitabine in patients with HER2-positive locally advanced or metastatic breast cancer (ZMC-ARX788-211)
Authors: Hu Xichun , Zhang Jian , Wang Leiping , Xia Gang , Ji Yanping , Xiong Gaozhun , Liang Xuejun , Yao Sulan , Tian Feng 
Published: February 2021

Abstract
Background: ARX788 is a novel antibody drug conjugate (ADC) that consists of a human epidermal growth factor receptor 2 (HER2) targeting monoclonal antibody (mAb) site-specifically conjugated with payload AS269, a highly potent tubulin inhibitor. Results from a phase 1 study (CTR20171162) in cohorts dosing from 1.1 mg/kg to 1.5 mg/kg demonstrated promising antitumor activity with an objective response rate (ORR) of 52.0% (26 of 50) in heavily pretreated patients (median 5 prior regimens) with HER2-positive metastatic breast cancer. Among patients with tyrosine-kinase inhibitors (TKIs) prior treatment, the ORR was 48.5% (16 of 33). In 1.5mg/kg Q3W cohort, ORR was 68.4% (13 of 19) and median progression-free survival (PFS) was not reached due to majority subjects were still under ARX788 treatment. Here we describe a phase II/III study evaluating the efficacy and safety of ARX788 vs Lapatinib and Capecitabine in patients with HER2-positive advanced breast cancer.
Study Description: ZMC-ARX788-211 (CTR20200713) is a randomized, multicenter, open-label, phase II/III trial comparing ARX788 vs Lapatinib and Capecitabine in patients with HER2-positive locally advanced or metastatic breast cancer. Approximately 440 patients (IHC3+ or ISH+) from 45 centers in China will be 1:1 randomized to receive ARX788 1.5 mg/kg every 3 weeks or Lapatinib plus Capecitabine until disease progression, intolerable toxicity, or death. Patients must have progression on ≥1 prior lines of HER2 therapy. Randomization will be stratified by therapy line (1 vs. &gt;1) and visceral metastasis (yes vs. no). The primary outcome measure is PFS per Independent Review Committee (IRC). Secondary outcome measures are overall survival (OS), PFS per investigators, ORR, disease control rate (DCR), duration of response (DOR), safety, immunogenicity and population pharmacokinetic. Two interim analyses are planned for the study. The first interim analysis will be performed when 160 patients have completed Cycle 4 assessment to detect potential early futility trends. The second interim analysis will be performed when 2/3 of the IRC assessed PFS events have occurred, in which early superiority will be declared if the P-value crossed the O’Brien Fleming boundary, and sample size will be recalculated if the conditional power is promising but below 80%. Global phase II/III trial of ARX788 to include sites in US and other regions is under planning.
Citation Format: Xichun Hu, Jian Zhang, Leiping Wang, Gang Xia, Yanping Ji, Gaozhun Xiong, Xuejun Liang, Sulan Yao, Feng Tian. A randomized, multicenter, open-label phase II/III study of ARX788 vs Lapatinib and Capecitabine in patients with HER2-positive locally advanced or metastatic breast cancer (ZMC-ARX788-211) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-57.