A Study to Evaluate ALN-BCAT in Patients With Hepatocellular Carcinoma

• ALN-BCAT (Drug): Administered by intravenous (IV) infusion
• Pembrolizumab (Drug), also known as Keytruda, MK-3475: Administered by intravenous (IV) infusion

Primary outcomes

• Frequency of Adverse Events (AEs) [From the time of first dose of study drug administration to 30-37 days after the last dose]
• Severity of AEs [From the time of first dose of study drug administration to 30-37 days after the last dose]
• Dose Escalation: Occurrence of Dose-limiting Toxicities (DLTs) [From the time of first dose of study drug administration up to 21 days]
• Dose Expansion: Antitumor Activity as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [Up to 30-37 Days after the last dose]

Secondary outcomes

• Concentrations of ALN-BCAT in Plasma [Up to the end of the last study drug administration]: Area Under the Plasma Concentration-time Curve (AUC), Maximum Observed Plasma Concentration (Cmax) Time to Maximum Plasma Concentration (Tmax)
• Percent Change in Gene that Encodes ß-catenin Protein (CTNNB1) Messenger Ribonucleic Acid (mRNA) Expression Comparing Pre- treatment with On-treatment Tumor Samples [Up to 30 days]
• Dose Escalation: Antitumor Activity as assessed by RECIST v1.1 [Up to 30-37 Days after the last dose]

Sex: All, ages: 18 Years to any

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

• Medical Director, Study director, Alnylam Pharmaceuticals