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

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