A Study of RO5137382 (GC33) in Patients With Advanced or Metastatic Hepatocellular Carcinoma

• Overall survival [ Time Frame: approximately 32 months ] [ Designated as safety issue: No ]
• Time to progression (TTP): Time from randomization to first documented disease progression [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
• Disease control rate (DCR): Complete response, partial response or stable disease lasting at least 6 weeks [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
• Pharmacokinetics: Serum concentrations (Cmax,Cmin) [ Time Frame: Multiple sampling pre- and post-dose Days 1 and 8 Cycle 1, Day 1 Cycle 6, pre-dose Day 1 Cycles 2-11 ] [ Designated as safety issue: No ]
• GPC-3 expression in tumor tissue (biopsy) by immunohistochemistry (IHC) assay [ Time Frame: at screening ] [ Designated as safety issue: No ]

This randomized, placebo-controlled, multicenter study will evaluate the efficacy and safety of RO5137382 (GC33) in previously treated patients with unresectable advanced or metastatic hepatocellular carcinoma. Patients will be stratified according to the level of GPC-3 expression in tumors and randomized to receive either RO5137382 (1600 mg intravenously) or placebo on Days 1 and 8 of Cycle 1 and every 2 weeks thereafter. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

• Drug: RO5137382
  1600 mg iv Day 1 and 8, and every 2 weeks thereafter
  Other Name: GC33
• Drug: Placebo
  iv Days 1 and 8, and every 2 weeks thereafter

• Experimental: RO5137382 (GC33)
  Intervention: Drug: RO5137382
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Histologically confirmed hepatocellular carcinoma (without fibro-lamellar subtype)
• Prior treatment with at least 1 systemic agent, with documented progressive disease after systemic agent(s), or documented adverse event(s) associated with prior systemic agent(s) that resulted in discontinuance of that (those) agent(s)
• Not a candidate for curative treatments (e.g. resection, transplantation)
• Child-Pugh A (score of 5-6)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate hematologic, hepatic and renal function
• Ability to provide, for central review, a tumor tissue sample to determine the level of GPC-3 expression by IHC
• Measurable disease by RECIST criteria

Exclusion Criteria:

• Child Pugh B or C
• Known hepatocellular carcinoma with fibro-lamellar histology
• Known brain or leptomeningeal metastases
• Active infectious diseases requiring treatment except for hepatitis B and C
• History of organ allograft including liver transplant
• Anticipated or ongoing administration of anticancer therapies other than those administered in this study
• Anticancer treatment within 2 weeks prior to entering the study
• Patients who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies
• Patients receiving interferon therapy
• Pregnant or lactating women
• Known HIV positivity or AIDS-related illness
• History of significant hypersensitivity to similar agents (monoclonal antibody, protein-included drugs, Chinese hamster ovary products)