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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: ATG-008

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Changchun, China
    • The First Hospital of Jilin University
  • Changsha, China
    • Hunan Province Oncology Hospital
  • Chongqing, China
    • Daping Hospital
  • Chongqing, China
    • The first hospital of Chongqing medical university
  • Fuzhou, China
    • Xiehe Hospital of Fujian Medical University
  • Guangzhou, China
    • Nanfang Hospital of Nanfang Medical University
  • Hangzhou, China
    • The First Affiliated Hospital of Zhejiang University
  • Hangzhou, China
    • Zhejiang Province Oncology Hospital
  • Hefei, China
    • The First Affiliated Hospital of Anhui Medical University
  • Hefei, China
    • The Second Affiliated Hospital of Anhui Medical University
  • Nanning, China
    • The First Affiliated Hospital of Guangxi Medical University
  • Shanghai, China
    • Zhongshan Hospital of Fudan University
  • Shanghai, China
    • Oncology Hospital of Fudan University
  • Shenyang, China
    • General Hospital of the Northern War Zone of the Chinese People's Liberation Army
  • Xi'an, China
    • Tangdu Hospital of China PLA fourth medical university
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Oncology Hospital of Haerbin Medical University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • China People PLA 81 Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital Sichuan University
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Yunnan Cancer Hospital
• Korea, Republic of
  • Busan, Korea, Republic of
    • Dong-A University Hospital
  • Busan, Korea, Republic of
    • Pusan National Univ. Hospital
  • Daegu, Korea, Republic of
    • Kyungpook National Univ. Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • Taipei Medical University Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital-Linkuo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged from 18 to 70 years (inclusive) at the time when the ICF is signed.
2. Confirmed diagnosis of HCC.
3. Unresectable stage B or C HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging.
4. HBV positive by serum test.
5. Received at least one prior line of systemic therapy.
6. ECOG performance status score of 0 or 1.
7. Satisfactory serum chemistry results
8. Adequate bone marrow function
9. Child-Pugh A without encephalopathy.
10. 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:

1. Symptomatic central nervous system metastases.
2. Locoregional HCC therapy, systemic chemotherapy, hormonal therapy or investigational therapy within 4 weeks prior to Screening.
3. Life expectancy of less than 3 months.
4. Prior therapy with mTOR inhibitors.
5. Prior organ transplant.
6. Persistent diarrhea or malabsorption.
7. Clinically significant bleeding.
8. Known history of human immunodeficiency virus (HIV) infection.
9. Uncontrolled intercurrent illness.
10. Any condition that confounds the ability to interpret data from the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: ATG-008; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Potential biomarkers in plasma and tumor tissues	The changes in potential biomarkers including but not limited to TORC1/TORC2 activity in peripheral blood samples and tumor tissue following treatment with ATG-008	365 DAYS
Additional metabolites of ATG-008 in plasma and urine	Additional metabolites of ATG-008 in plasma and urine, and the extent of their urinary excretion/clearance	Day 1 - Day 15

Collaborators and Investigators

• Sponsor: Antengene Therapeutics Limited
• Investigators: Study Director: Stephen Xie, PhD, Medical Monitor

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2018
• Primary Completion (Actual): August 3, 2022
• Study Completion (Actual): August 3, 2022

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: HCC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: ATG-008-HCC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No