Phase I study of AMG 211/MEDI-565 administered as continuous intravenous infusion for relapsed/refractory gastrointestinal (GI) adenocarcinoma.

TPS3097 Background: The bispecific CD19-directed CD3 T-cell engager (BiTE(R)) blinatumomab was recently approved by FDA as single-agent immunotherapy for patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL. The clinical activity of blinatumomab seen with 4-week infusion regimen provides rationale for BiTE administration as continuous intravenous infusion (cIV). Experience with an EpCAM-directed BiTE first-in-human study (FIH) suggests that in solid tumor indications dose levels achieving exposure comparable to 50% or even 90% of the maximal effective concentration in in vitro might be needed to observe substantial anti-tumor activity translating into objective response (Fiedler et al, J Clin Oncol 30, 2012, abstr 2504). The CEA-directed BiTE (MEDI-565, AMG 211) inhibited the growth of CEA-expressing cancer cells in various cancer models in the presence of CD3+ T-cells and has been explored as an intermittent 3-hour infusion for 5 subsequent days in a FIH study (NCT01...