Clinical trial NCT06600321: A Study to Evaluate ALN-BCAT in Patients With Hepatocellular Carcinoma
Official title: A Phase 1 Study of ALN-BCAT as Monotherapy and in Combination With Pembrolizumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Hepatocellular Carcinoma
Metastatic Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma (HCC)
Pembrolizumab
CTNNB1
Liver disease
Liver cancer
Liver neoplasms
Carcinoma, hepatocellular
WNT pathway activating
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Frequency of Adverse Events (AEs)
timeFrame: From the time of first dose of study drug administration to 30-37 days after the last dose
measure: Severity of AEs
timeFrame: From the time of first dose of study drug administration to 30-37 days after the last dose
measure: Dose Escalation: Occurrence of Dose-limiting Toxicities (DLTs)
timeFrame: From the time of first dose of study drug administration up to 21 days
measure: Dose Expansion: Antitumor Activity as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: Up to 30-37 Days after the last dose
Secondary outcomes:
measure: Concentrations of ALN-BCAT in Plasma
timeFrame: Up to the end of the last study drug administration
measure: Percent Change in Gene that Encodes ß-catenin Protein (CTNNB1) Messenger Ribonucleic Acid (mRNA) Expression Comparing Pre- treatment with On-treatment Tumor Samples
timeFrame: Up to 30 days
measure: Dose Escalation: Antitumor Activity as assessed by RECIST v1.1
timeFrame: Up to 30-37 Days after the last dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Ann Arbor
country: United States
facility: Clinical Trial Site
state: Michigan
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Cleveland
country: United States
facility: Clinical Trial Site
state: Ohio
city: Pittsburgh
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Dallas
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: San Antonio
country: United States
facility: Clinical Trial Site
state: Texas
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: