A phase Ib study to assess the safety of lexatumumab, a human monoclonal antibody that activates TRAIL-R2, in combination with gemcitabine, pemetrexed, doxorubicin or FOLFIRI

14006 Background: Lexatumumab (HGS-ETR2) is a fully-human agonistic monoclonal antibody that targets and activates the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 2 (TRAIL-R2). TRAIL-R2 is a member of the Tumor Necrosis Factor Receptor (TNFR) superfamily that, when activated, induces apoptosis via the extrinsic pathway. Lexatumumab shows promising anti-tumor activity in preclinical models, particularly in combination with chemotherapeutic agents. Single-agent lexatumumab was well-tolerated in phase I trials. This is the first study of the safety of a TRAIL-R2 agonist in combination with chemotherapy. Methods: Patients for whom gemcitabine, pemetrexed, doxorubicin or FOLFIRI was considered an appropriate treatment received one of the full-dose chemotherapy regimens plus lexatumumab every 2 weeks (for gemcitabine and FOLFIRI) or 3 weeks (for pemetrexed and doxorubicin). Four to 6 patients were treated with 5 mg/kg lexatumumab in each chemotherapy cohort prior to dose escalation to 10 mg...