Phase I evaluation of the safety of conatumumab (AMG 655) in combination with AMG 479 in patients (pts) with advanced, refractory solid tumors.

3102 Background: Preclinical studies show that evasion of death receptor (DR)-mediated apoptosis may depend on intact growth factor signaling. DR agonists have not previously been combined with IGF-1R inhibitors in published clinical studies. The combination may yield synergistic targeted antitumor activity without added toxicity. This study combined 2 investigational, fully human monoclonal antibodies: conatumumab, a human DR5 agonist; and AMG 479, an IGF-1R antagonist. Methods: Eligible pts had locally advanced or metastatic chemotherapy refractory solid tumors, ECOG PS of 0 or 1, and adequate glycemic control if diabetic. Pts enrolled into 3 sequential dose cohorts and received conatumumab 1, 3, or 15 mg/kg IV and AMG 479 18 mg/kg IV on day 1 of each Q3W cycle. Dose escalation was based on <33% incidence of dose-limiting toxicities (DLT) during the first cycle. Study endpoints included: dose determination, adverse event (AE) incidence, DLT, anti-drug antibodies, and pharmacokinetics (PK) of both drugs....