An open-label, dose-escalation phase I study to evaluate RC48-ADC, a novel antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer.

1030Background: There is still urgent medical needs for new therapeutics in the patients with metastatic breast cancer (MBC) and other solid tumors with HER2 overexpression. RC48-ADC is an antibody-drug conjugate drug with a novel humanized anti-HER2 antibody conjugated to monomethyl auristatin E (MMAE) through a cleavable linker. Preclinical data in various animal models, including breast cancer, gastric cancer and ovarian cancer, suggested excellent antitumor efficacy. Methods: It was an open-label, single-center, phase I study. Eligible pts (18-65 years) were confirmed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) as HER2-positive (IHC 2+/FISH+ or IHC 3+) MBC. A 3+3 dose-escalation was conducted with a 28-day window to evaluate dose limiting toxicity (DLT). DLT was mainly defined as Grade 4 neutropenia effectively managed with symptomatic treatment, Grade 3 neutropenia accompanied by infection and Grade 3 non-hematological toxicity. Tumor response was accessed per RECIST 1...