Dual TORC1/TORC2 Inhibitor ATG-008 (CC-223) in HBV Positive Advanced Hepatocellular Carcinoma (HCC) Subjects
- Registration Number
- NCT03591965
- Lead Sponsor
- Antengene Therapeutics Limited
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 73
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ATG-008 ATG-008 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.
- Primary Outcome Measures
Name Time Method Cmax Day 1 - Day 15 Peak Plasma Concentration (Cmax)
AUC Day 1 - Day 15 Area under the plasma concentration versus time curve (AUC)
The incidence of treatment emergent adverse events (TEAEs) & SAE assessed by CTCAE v4.03 365 DAYS The treatment emergent adverse events (TEAEs) \& SAE case No. in total subject No.
ORR 365 DAYS Percentage of subjects with PR, or CR
- Secondary Outcome Measures
Name Time Method OS 365 DAYS Kaplan-Meier estimate of Overall Survival
TTP 365 DAYS The time from the first dose date until disease progression
6, 9 and 12 month of survival rate 365 DAYS Percentage of patients alive
PFS 365 DAYS The time from the first dose date until disease progression or death from any cause
DCR 365 DAYS The percentage of subjects with CR, or PR or stable disease (SD)
DOR 365 DAYS 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
TTR 365 DAYS The time from the first dose date to the first documentation of response of PR or better.
Trial Locations
- Locations (30)
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Pusan National Univ. Hospital
🇰🇷Busan, Korea, Republic of
China Medical University Hospital
🇨🇳Taichung, Taiwan
Oncology Hospital of Fudan University
🇨🇳Shanghai, China
Tangdu Hospital of China PLA fourth medical university
🇨🇳Xi'an, China
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Kyungpook National Univ. Hospital
🇰🇷Daegu, Korea, Republic of
West China Hospital Sichuan University
🇨🇳Chengdu, Sichuan, China
Yunnan Cancer Hospital
🇨🇳Kunming, Yunnan, China
The first Hospital of Jilin University
🇨🇳Changchun, China
Hunan Province Oncology Hospital
🇨🇳Changsha, China
Xiehe Hospital of Fujian Medical University
🇨🇳Fuzhou, China
Nanfang Hospital of Nanfang Medical University
🇨🇳Guangzhou, China
China People PLA 81 Hospital
🇨🇳Nanjing, Jiangsu, China
The first affiliated Hospital of Zhejiang University
🇨🇳Hangzhou, China
Zhejiang Province Oncology Hospital
🇨🇳Hangzhou, China
The second affiliated hospital of Anhui medical university
🇨🇳Hefei, China
The first affiliated hospital of Guangxi Medical University
🇨🇳Nanning, China
Zhongshan Hospital of Fudan University
🇨🇳Shanghai, China
General Hospital of the Northern War Zone of the Chinese People's Liberation Army
🇨🇳Shenyang, China
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
Oncology Hospital of Haerbin Medical University
🇨🇳Harbin, Heilongjiang, China
Daping Hospital
🇨🇳Chongqing, China
The first hospital of Chongqing medical university
🇨🇳Chongqing, China
The first affiliated hospital of Anhui medical university
🇨🇳Hefei, China
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Chang Gung Memorial Hospital-Linkuo
🇨🇳Taoyuan, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan