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

Phase 1
Recruiting
Conditions
Advanced Hepatocellular Carcinoma
Metastatic Hepatocellular Carcinoma
Interventions
Registration Number
NCT06600321
Lead Sponsor
Alnylam Pharmaceuticals
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
158
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Monotherapy: Dose ExpansionALN-BCATPatients will be administered multiple doses of ALN-BCAT.
Monotherapy: Dose EscalationALN-BCATPatients will be administered multiple doses of ALN-BCAT.
Combination Therapy: Dose EscalationALN-BCATPatients will be administered multiple doses of ALN-BCAT in combination with pembrolizumab.
Combination Therapy: Dose ExpansionALN-BCATPatients will be administered multiple doses of ALN-BCAT in combination with pembrolizumab.
Combination Therapy: Dose ExpansionPembrolizumabPatients will be administered multiple doses of ALN-BCAT in combination with pembrolizumab.
Combination Therapy: Dose EscalationPembrolizumabPatients will be administered multiple doses of ALN-BCAT in combination with pembrolizumab.
Primary Outcome Measures
NameTimeMethod
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 AEsFrom 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 Outcome Measures
NameTimeMethod
Concentrations of ALN-BCAT in PlasmaUp 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 SamplesUp to 30 days
Dose Escalation: Antitumor Activity as assessed by RECIST v1.1Up to 30-37 Days after the last dose

Trial Locations

Locations (1)

Clinical Trial Site

🇺🇸

San Antonio, Texas, United States

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