Dual TORC1/TORC2 Inhibitor ATG-008 (CC-223) in HBV Positive Advanced Hepatocellular Carcinoma (HCC) Subjects

Study Overview
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Brief Summary
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This is an Asian multi-regional clinical trial (MRCT) in which ATG-008 will be administered orally to hepatitis B positive (HBV+) HCC subjects who have received at least one prior line of systemic therapy. It is designed as an open-label phase 2 trial evaluating the pharmacokinetics (PK), safety, tolerability and efficacy of oral ATG-008 administered daily until the radiologic disease progression (according to RECIST 1.1) or intolerable toxicity.

Official Title
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An Open-label Phase 2 Trial of Dual TORC1/TORC2 Inhibitor ATG-008 in HBV+ Advanced Hepatocellular Carcinoma (HCC) Subjects Who Have Received at Least One Prior Line of Systemic Therapy (TORCH)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: ATG-008


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged from 18 to 70 years (inclusive) at the time when the ICF is signed. Confirmed diagnosis of HCC. Unresectable stage B or C HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging. HBV positive by serum test. Received at least one prior line of systemic therapy. ECOG performance status score of 0 or 1. Satisfactory serum chemistry results Adequate bone marrow function Child-Pugh A without encephalopathy. All subjects who participated in the study had to take reliable contraceptive measures within the trial and 3 months of after the trial. Exclusion Criteria: Symptomatic central nervous system metastases. Locoregional HCC therapy, systemic chemotherapy, hormonal therapy or investigational therapy within 4 weeks prior to Screening. Life expectancy of less than 3 months. Prior therapy with mTOR inhibitors. Prior organ transplant. Persistent diarrhea or malabsorption. Clinically significant bleeding. Known history of human immunodeficiency virus (HIV) infection. Uncontrolled intercurrent illness. Any condition that confounds the ability to interpret data from the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATG-008<br>To enroll approximately 40 hepatitis B virus (HBV) positive, unresectable HCC subjects who have previously received at least one prior line of systemic therapy. Among which, approximately 20 subjects will receive oral ATG-008 at an initial dose of 45 mg, once daily (QD) and another approximately 20 subjects will receive oral ATG-008 at an initial dose of 20 mg, twice daily (BID). The pharmacokinetic (PK) samples will be collected from 10 subjects each in the two dose groups. | Drug: ATG-008<br>* Approximately 20 subjects will receive oral ATG-008 at an initial dose of 45 mg/QD and another 20 subjects will receive oral ATG-008 at an initial dose of 20mg/BID for 28 days each cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Peak Plasma Concentration (Cmax) | Day 1 - Day 15 | 
| AUC | Area under the plasma concentration versus time curve (AUC) | Day 1 - Day 15 | 
| The incidence of treatment emergent adverse events (TEAEs) & SAE assessed by CTCAE v4.03 | The treatment emergent adverse events (TEAEs) & SAE case No. in total subject No. | 365 DAYS | 
| ORR | Percentage of subjects with PR, or CR | 365 DAYS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Kaplan-Meier estimate of Overall Survival | 365 DAYS | 
| TTP | The time from the first dose date until disease progression | 365 DAYS | 
| PFS | The time from the first dose date until disease progression or death from any cause | 365 DAYS | 
| DCR | The percentage of subjects with CR, or PR or stable disease (SD) | 365 DAYS | 
| DOR | The time from the criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented | 365 DAYS | 
| TTR | The time from the first dose date to the first documentation of response of PR or better. | 365 DAYS | 
| 6, 9 and 12 month of survival rate | Percentage of patients alive | 365 DAYS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC