Phase 1b Study Of R05137382/Gc33 In Combination With Sorafenib In Patients With Advanced Hepatocellular Carcinoma (Hcc) (Nct00976170).

4100 Background: GC33 is a recombinant humanized monoclonal antibody against Glypican-3 (GPC3) which is highly expressed in HCC. GC33 elicits antibody-dependent cellular cytotoxicity against human HCC cell lines in vitro. GC33 and sorafenib showed an additive anti-tumor effect in xenograft mouse model. This is a phase I dose escalation study to evaluate safety/tolerability and pharmacokinetics (PK) of combination therapy in HCC. Methods: In a 3+3 design dose escalation design GC33 given intravenously 2.5, 5 and 10 mg/kg weekly, then 1,600 mg every 2 weeks, and then 1,600mg weekly, all in combination with sorafenib 400mg twice daily. Patients with advanced HCC patients, age ≥18, ECOG 0-1, Child-Pugh A, adequate organ functions (platelets ≥ 100 x109/L, ANC ≥ 1500, AST/ALT ≤ 5 x ULN, Bilirubin ≤ 1.5 mg/dL, and creatinine ≤ 2 x ULN), and no prior therapy with sorafenib were eligible. Primary endpoints were safety and tolerability and secondary endpoints PK of GC33 and sorafenib and efficacy. Tumor assessment ...