Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Ramucirumab and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (AFP) Following First-Line Therapy With Sorafenib

• A diagnosis of HCC based on histopathologic findings, or a diagnosis of cirrhosis and a tumor with classical HCC imaging characteristics.

• Sorafenib was the only systemic therapy for HCC and was discontinued for disease progression or intolerance (Main Global and MEE Cohorts only).

• The participant received ≤2 prior systemic therapy regimen, excluding prior sorafenib or chemotherapy, for the treatment of HCC (OLE Cohort only).

• ≥1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 that has not been previously treated with locoregional therapy. A participant with a lesion(s) that has previously been treated with locoregional therapy is also eligible, if the lesion has documented progression after locoregional treatment and is measureable.

• Child-Pugh score \<7 (Child-Pugh Class A).

• Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy.

• Baseline AFP ≥400 nanograms/milliliter.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Resolution of all clinically significant toxic effects of prior therapy.

• Total bilirubin ≤1.5 times upper limit of normal value (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤5 × ULN.

• Creatinine clearance ≥60 milliliters/minute.

• Urinary protein is ≤1+ on dipstick or routine urinalysis or 24-hour urine demonstrating \<1 gram of protein.

• Absolute neutrophil count ≥1.0 × 10\^9/Liter, hemoglobin ≥9 grams/deciliter, and platelets ≥75 × 10\^9/Liter.

• International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) ≤5 seconds above the ULN.

• Surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method.

• If a woman of childbearing potential, a negative serum pregnancy test prior to randomization.

• Willing to provide blood for research. The participant has provided signed informed consent prior to any study specific procedures and is amenable to compliance with protocol schedules and testing.