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.

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.

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.

A randomized, open label, multi-center phase 2-2i neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer.

A prospective, single-arm, single-center phase 2 clinical study of recombinant humanized anti-HER2 monoclonal antibody-AS269 conjugate (ARX788) in the treatment of HER2-positive breast cancer patients with brain metastases.

A single-arm, single-center phase 2 clinical study of recombinant humanized anti-HER2 monoclonal antibody-AS269 conjugate (ARX788) in the treatment of unresectable and/or metastatic breast cancer with low expression of HER2.

Efficacy and safety of pyrotinib maleate combined with ARX788 neoadjuvant treatment in stage 2-2I HER2-positive breast cancer patients who have poor outcomes after treatment with trastuzumab and pertuzumab.