Phase I study of anti-mesothelin antibody drug conjugate anetumab ravtansine (AR).

2509Background: AR (BAY 94-9343) comprises a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DMR. A phase I study was conducted in patients (pts) with advanced solid tumors. Methods: Eligible pts with solid tumors refractory to standard treatment, adequate organ function, and ECOG performance status (PS) ≤ 1 were enrolled. AR was administered IV on 2 schedules: every 21 days (q3w) in 45 pts (21 mesothelioma [Meso], 9 pancreatic, 5 breast, 4 ovarian cancer [OC], 6 other) at doses ranging from 0.15 to 7.5 mg/kg and in an expansion cohort at 6.5 mg/kg (12 Meso and 20 OC); and weekly (qw) in 71 pts (31 Meso and 40 OC) randomized to either 1.8 mg/kg or 2.2 mg/kg. Pts were assessed for AEs weekly C1-C3 and on D1 in subsequent cycles. Tumor response was assessed q6w C1-C8 and q12w thereafter. Mesothelin expression in archival tumor samples was assessed by IHC (SP74, Ventana). Results: A total of 147 pts were evaluable: 64% female, mean age 61 yrs (range 18-88), PS...