A phase 1 study of ACE-Breast-01 [ZMC-ARX788111 (CTR20171162)] to test the safety, PK, and antitumor activity of ARX788 in patients in China with HER2-positive metastatic breast cancer (MBC) whose disease had progressed on prior anti-HER2 treatments. The study includes dose escalation(N=69) to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) in patients with HER2-positive MBC.

The MTD of ARX788 was not reached at doses of up to 1.50 mg/kg every 3 weeks. the RP2D in breast cancer studies was determined to be 1.50 mg/kg every 3 weeks. 33 of the 69 (47.83%) patients had an objective partial tumor response. For ARX788 1.50 mg/kg every 3 weeks, the objective response rate was 65.52% [19/29, 95% confidence interval (CI), 45.70-82.10], the disease control rate was 100.00% (95% CI, 81.20-100.00), and the median progression-free survival was 17.02 months (95% CI, 10.09-not reached).

A phase 1 study in HER2-positive advanced ug/GEJ adenocarcinoma was initiated to evaluate the safety and efficacy of ARX788. There were 22 males (73.3%) and 8 females (26.7%). Twenty-two (73.3%) had gastric adenocarcinoma,and the rest (26.7%) had GEJ adenocarcinoma. Twenty-seven patients (90%) underwent prior trastuzumab-containing therapy,eight of whom progressed within 6 months in the adjuvant or neoadjuvant phase. Twelve (40%) were treated with 2 or more lines of therapy (26) and eight of whom had 3 or more lines. All patients were treated with platinum-based and fluorouracil regimens,and eight with taxanes and three with irinotecan. Most participants (73.3%) had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1. All of them had at least one dose of ARX788,of whom 9 patients received 1.3 mg/kg,14 received 1.5 mg/kg,and 7 received 1.7 mg/kg ARX788.

Incurable, locally advanced, or metastatic HER2-positive (immunohistochemistry [IHC] 3+ and/or fluorescence in situ 1 hybridization [FISH]-positive) breast cancer that progressed on greater and or 2 equal to two prior anti-HER2 treatment(s) in the advanced disease setting and 3 who provided written informed consent, patients had an Eastern 4 Cooperative Oncology Group (ECOG) performance status of 0-1.

Patients with HER2-positive MBC received ARX788 at doses of 0.33, 0.66, 0.88, 1.10, 1.30, or 1.50 mg/kg every 3 weeks, or 0.88, 1.10, or 1.30 mg/kg every 4 weeks. The dose-limiting toxicity (DLT) was assessed for 84 days for pulmonary toxicity and at a duration of one cycle (21 or 28 days) for other toxicities. In total, 69 patients were enrolled. No DLT or drug-related deaths occurred.