A phase 1 multicenter, dose expansion study of ARX788 as monotherapy in patients with HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma (ACE-Gastric-01).

person Yang Zhang Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Yang Zhang, Miaozhen Qiu, Jufeng Wang, Yanqiao Zhang, Xianglin Yuan, Tao Zhang, Jinchun Yan, Gaozhun Xiong, Yanping Ji, Xuejun Liang, Gang Xia, Rui-hua Xu

Authors person Yang Zhang Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Yang Zhang, Miaozhen Qiu, Jufeng Wang, Yanqiao Zhang, Xianglin Yuan, Tao Zhang, Jinchun Yan, Gaozhun Xiong, Yanping Ji, Xuejun Liang, Gang Xia, Rui-hua Xu Organizations Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China, Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China, Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong Universtiy of Science and Technology, Wuhan, China, Ambrx, Inc, Princeton Junction, NJ, NovoCodex Biopharmaceuticals, Shaoxing, China, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Novocodex Biopharmaceuticals Background: ARX788 is a novel antibody drug conjugate (ADC) that consists of human epidermal growth factor receptor 2 (HER2) targeted monoclonal antibody (mAb) linked to a cytotoxic payload, AS269, a highly potent tubulin inhibitor. In a phase 1 study of ARX788 in HER2-positive advanced breast cancer (CTR20171162/ACE-Breast-01), the objective response rate (ORR) was 74 % (14/19) at 1.5 mg/kg Q3W. Here we present the safety, tolerability, and antitumor activity of ARX788 in HER2-positive advanced gastric and gastroesophageal junction (GEJ) cancer in the phase 1 (ACE-Gastric-01) study. Methods: participants with HER2+ gastric/GEJ cancer were administrated with ARX788 intravenously at dose levels of 1.3, 1.5, and 1.7 mg/kg Q3W to determine the maximum tolerated dose and recommended phase 2 dose; and to evaluate the antitumor activity. Efficacy endpoints included objective response rate (ORR) and disease control rate (DCR) per RECIST v1.1. Results: As of Jan 29, 2021, a total of 23 participants including 9 at the 1.3 mg/kg and 14 at the 1.5 mg/kg received at least one dose of ARX788. All patients were heavily treated previously. The confirmed ORR was 42.9% and 46.2% at the 1.3 and 1.5 mg/kg, respectively. As of the cut-off date, six participants were still under treatment with two of them were treated for longer than 12 months. Most AEs were grade 1 or 2 and were manageable. There were 2 drug-related grade 3 AEs and no grade 4 or 5 AEs occurred. No DLT was observed and the MTD was not reached. The dose expansion at the 1.7 mg/kg Q3W cohort is still ongoing and the mature data will be presented later. Conclusions: ARX788 was well tolerated with promising antitumor activity in patients with HER2-positive advanced gastric and GEJ adenocarcinoma. Clinical trial information: CTR20190639. Efficacy [n (%)] 1.3 mg/kg N=7 1.5 mg/kg N=13 All N=20 Confirmed ORR 3 (42.9) 6 (46.2) 9 (45.5) DCR 4 (57.1) 6 (46.2) 10 (50.0) Safety [n (%)] N=9 N=14 N=23 TEAE (Grade 1-2) 9 (100) 13 (92.2) 22 (95.7) TEAE (≥Grade 3) 3 (33.3) 3 (21.4) 6 (26.1) ----- Drug-related AE (≥Gr3) 2 (22.2) 0 2 (8.7) SAE 4 (44.4) 2 (14.3) 6 (26.1) ----- Drug-related SAE 2 (22.2%) 0 2 (8.7)