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

June 16, 2026 updated by: Alnylam Pharmaceuticals

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

158

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Milan, Italy, 20132
        • Recruiting
        • Clinical Trial Site
      • Rozzano, Italy, 20089
        • Recruiting
        • Clinical Trial Site
      • Verona, Italy, 37134
        • Recruiting
        • Clinical Trial Site
  • South Korea
      • Busan, South Korea, 49241
        • Recruiting
        • Clinical Trial Site
      • Seongnam, South Korea, 13496
        • Recruiting
        • Clinical Trial Site
      • Seongnam, South Korea, 13620
        • Recruiting
        • Clinical Trial Site
      • Seoul, South Korea, 03722
        • Recruiting
        • Clinical Trial Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Clinical Trial Site
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • Clinical Trial Site
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Clinical Trial Site
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Clinical Trial Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Clinical Trial Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • Clinical Trial Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • Clinical Trial Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Clinical Trial Site
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Clinical Trial Site
      • New York, New York, United States, 10032
        • Completed
        • Clinical Trial Site
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Clinical Trial Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • Clinical Trial Site
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • Clinical Trial Site
      • Houston, Texas, United States, 77030
        • Recruiting
        • Clinical Trial Site
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • Clinical Trial Site
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Monotherapy: Dose Escalation
Patients will be administered multiple doses of ALN-BCAT.
Drug: ALN-BCAT
Administered by intravenous (IV) infusion
Experimental: Monotherapy: Dose Expansion
Patients will be administered multiple doses of ALN-BCAT.
Drug: ALN-BCAT
Administered by intravenous (IV) infusion
Experimental: Combination Therapy: Dose Escalation
Patients will be administered multiple doses of ALN-BCAT in combination with pembrolizumab.
Drug: ALN-BCAT
Administered by intravenous (IV) infusion
Drug: Pembrolizumab
Administered by intravenous (IV) infusion
Other Names:
  • Keytruda
  • MK-3475
Experimental: Combination Therapy: Dose Expansion
Patients will be administered multiple doses of ALN-BCAT in combination with pembrolizumab.
Drug: ALN-BCAT
Administered by intravenous (IV) infusion
Drug: Pembrolizumab
Administered by intravenous (IV) infusion
Other Names:
  • Keytruda
  • MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
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
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
Up to 30-37 Days after the last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concentrations of ALN-BCAT in Plasma
Time Frame: 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)
Up to the end of the last study drug administration
Dose Escalation: Antitumor Activity as assessed by RECIST v1.1
Time Frame: Up to 30-37 Days after the last dose
Up to 30-37 Days after the last dose
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
Up to 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alnylam Pharmaceuticals

Investigators

  • Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 30, 2024

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

October 31, 2027

Study Registration Dates

First Submitted

September 13, 2024

First Submitted That Met QC Criteria

September 13, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

June 17, 2026

Last Update Submitted That Met QC Criteria

June 16, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-BCAT-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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