RecruitingInterventionalPhase 1

A Phase 1 Study of ALN-BCAT as Monotherapy and in Combination With Pembrolizumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma

NCT ID: NCT06600321Sponsor: Alnylam PharmaceuticalsLast updated: 2026-06-17

Summary

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.

Arms & interventions

DrugALN-BCAT
Administered by intravenous (IV) infusion
DrugPembrolizumab
Administered by intravenous (IV) infusion

Outcome measures

Primary

Frequency of Adverse Events (AEs)
Time frame: From the time of first dose of study drug administration to 30-37 days after the last dose
Severity of AEs
Time frame: 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)
Time frame: 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)
Time frame: Up to 30-37 Days after the last dose

Secondary

Concentrations of ALN-BCAT in Plasma
Time frame: Up to the end of the last study drug administration
Percent Change in Gene that Encodes ß-catenin Protein (CTNNB1) Messenger Ribonucleic Acid (mRNA) Expression Comparing Pre- treatment with On-treatment Tumor Samples
Time frame: Up to 30 days
Dose Escalation: Antitumor Activity as assessed by RECIST v1.1
Time frame: Up to 30-37 Days after the last dose

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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

Study locations (16)

Clinical Trial Site

Phoenix, Arizona, 85054

Recruiting

Clinical Trial Site

La Jolla, California, 92037

Recruiting

Clinical Trial Site

Los Angeles, California, 90033

Recruiting

Clinical Trial Site

Jacksonville, Florida, 32224

Recruiting

Clinical Trial Site

Atlanta, Georgia, 30322

Recruiting

Clinical Trial Site

Chicago, Illinois, 60637

Recruiting

Clinical Trial Site

Ann Arbor, Michigan, 48109

Recruiting

Clinical Trial Site

Rochester, Minnesota, 55905

Recruiting

Clinical Trial Site

New York, New York, 10029

Recruiting

Clinical Trial Site

New York, New York, 10032

Completed

Clinical Trial Site

Cleveland, Ohio, 44106

Recruiting

Clinical Trial Site

Pittsburgh, Pennsylvania, 15232

Recruiting

Clinical Trial Site

Dallas, Texas, 75390

Recruiting

Clinical Trial Site

Houston, Texas, 77030

Recruiting

Clinical Trial Site

San Antonio, Texas, 78229

Recruiting

Clinical Trial Site

Richmond, Virginia, 23298

Recruiting