The purpose of the dose escalation part of the study is to characterize the safety and tolerability of ALN-BCAT as monotherapy and in combination with pembrolizumab; and to determine the recommended dose(s) for expansion (RDFE) of ALN-BCAT as monotherapy and in combination with pembrolizumab. The purpose of the dose expansion part of the of the study is to evaluate the antitumor activity of ALN-BCAT as monotherapy and in combination with pembrolizumab; to characterize the safety and tolerability of ALN-BCAT as monotherapy and in combination with pembrolizumab.

Inclusion Criteria:

• Has HCC confirmed histologically or cytologically, or, for patients with liver cirrhosis, clinically by the American Association for the Study of Liver Diseases (AASLD) criteria
• Has had at least one line of systemic therapy for unresectable advanced or metastatic disease
• Has at least one wingless-related integration site (WNT)-pathway activating mutation
• Child-Pugh class A or B7

Exclusion Criteria:

• Has fibrolamellar HCC, sarcomatoid HCC, or mixed cholangio-HCC tumors
• Has symptomatic extrahepatic disease
• Has received anti-cancer therapy or investigational drugs ≤3 weeks prior to the first dose of study drug

Note: other protocol defined inclusion / exclusion criteria apply