Advanced Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular carcinoma (HCC), Pembrolizumab, CTNNB1, Liver disease, Liver cancer, Liver neoplasms, Carcinoma, hepatocellular, WNT pathway activating
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.
Interventions
DRUGALN-BCAT
Administered by intravenous (IV) infusion
DRUGPembrolizumab
Administered by intravenous (IV) infusion
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy 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 /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Italy, South Korea, United States
Contacts
CONTACTAlnylam Clinical Trial Information Line
STUDY_DIRECTORMedical Director
Alnylam Pharmaceuticals
Outcome results
None listed