Safety and pharmacokinetics (PK) of AMG 479 in combination with erlotinib (E) or sorafenib (S) in patients (pts) with advanced solid tumors.

3018 Background: AMG 479, a fully human monoclonal antibody antagonist of IGF1R, showed activity in early clinical trials and additive effects with other therapies in preclinical models. This study examined adverse events (AEs), dose limiting toxicities (DLTs), PK, and WHO tumor response of AMG 479 combined with E, S, panitumumab (P), or gemcitabine (G). P and G results were shown previously (JCO 2008;26 abstr 3583). Methods: Eligible pts had advanced solid tumors, ECOG 0-2, and no hyperglycemia. A sequential 3+3 design was used. Pts received E (150 mg po QD) or S (400 mg po BID) with AMG 479 (6 or 12 mg/kg IV Q2W) until progression. CT scans were done every 8 weeks (wks). Results: A total of 25 pts enrolled and received AMG 479 + E (n = 12) or S (n = 13); median age (range) = 58 (41 to 74); 68% had ≥ 3 prior therapies; 44% were male. Most common emergent AEs are shown (Table). The S arm had no DLTs. There was 1 DLT (grade 4 thrombocytopenia) in the E arm at 12 mg/kg AMG 479. AMG 479 clearance (CL, mL/day...