An open-label, multicenter, phase Ib study to evaluate RC48-ADC in patients with HER2-positive metastatic breast cancer.

• DOI: 10.1200/jco.2018.36.15_suppl.1028
• Publication Date: 2018-09-05T14:14:13Z
• Authors: Binghe Xu; Jiayu Wang; Qingyuan Zhang; Yunjiang Liu; Ji Feng Feng; Wenxiang Wang; Jianmin Fang
• Keywords: Refractory (planetary science)

1028 Background: RC48-ADC is a novel HER2-targeting antibody–drug conjugate (ADC) that selectively delivers anticancer agent MMAE into HER2-overexpressing tumor cells. A Phase I study (NCT02881138) has preliminary demonstrated well tolerated and clear clinical activity in patients (pts) with metastatic breast cancer (MBC). Methods: This was phase Ib, open-label, multicenter 3 dose cohorts (1.5, 2.0 2.5mg/kg, Q2W). Eligible pts (18-70 years) were assessed HER2-positive (IHC 2+/FISH +, or IHC 3+) MBC, relapsed/refractory to prior standard treatment. Results: From Dec, 2016 Jan, 2018, 30 female (6 IHC2+/FISH+; 24 pretreated trastuzumab/chemotherapy enrolled for 1.5 mg/kg cohorts. Median age 53 years (range: 26-62). 19 (63.3%) received agents. 16 (53.3%) three more previous chemotherapy regimens setting. Disease control (CR+PR+SD) observed 29 of evaluable who RECIST 1.1 assessment (96.7%), 11 PR (ORR: 36.7%; 30-76% regression) 18 SD (60.0%) regression. CBR (CR + ≥6 months) presented 14 (46.7%). ORR 26.7% 46.7% the 1.5mg/kg cohorts, respectively; it 57.1% trastuzumab-naive 33.3% trastuzumab-pretreated (12 treated with≥3 chemotherapy). The common treatment-related adverse events (TRAEs) reported AST elevation (50.0%), ALT (43.3%), leucopenia (33.3%), neutropenia numbness (23.3%); most Grade 1-2 severity. Only (10%) Grade≤2 thrombocytopenia. TRAEs occurred 4 (13.3%), including (10%), (6.7%), (3.3%), (3.3%). No ≥4 AE observed. Pharmacokinetic analyses showed dose-dependent exposure 1-1.5 d half-life. Conclusions: manageable safety encouraging efficacy profiles MBC. Investigation 2.5 expansion cohort not yet been started. Results obtained from will determine whether 2.5mg/kg performed. Clinical trial information: NCT03052634.