Clinical Trials List
Protocol NumberATG-008-HCC-001
NCT Number(ClinicalTrials.gov Identfier)NCT03591965
2018-05-30 - 2022-12-31
Phase II
Recruiting5
ICD-10C22.0
Liver cell carcinoma
ICD-10C22
Malignant neoplasm of liver and intrahepatic bile ducts
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)
-
Trial Applicant
TAIWAN TIGERMED CONSULTING CO
-
Sponsor
Antengene Therapeutics Limited
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Rheun-Chuan Lee Division of Radiology
- Chung-Pin Li Digestive System Department
- San-Chi Chen Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Hung-Yao Chen Digestive System Department
- 蘇文邦 Digestive System Department
- Po-Heng Chuang Digestive System Department
- Cheng-Yuan Peng Digestive System Department
- 陳昇弘 Digestive System Department
- Wei-Fan Hsu Digestive System Department
- Hung-Wei Wang Digestive System Department
- Hsueh-Chou Lai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
楊再勝
Co-Principal Investigator
- Jen-Shi Chen Division of Hematology & Oncology
- Mengting Peng Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- Cheng-Lung Hsu Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
2 Recruiting
Audit
None
Co-Principal Investigator
- JA-DER LIANG Digestive System Department
- Chien-Hung Chen Division of General Internal Medicine
- 施怡倫 Division of Radiology
- YU-YUN SHAO Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Yu-Min Huang Division of Gastroenterological Surgery
- Long-Sheng Lu Division of Radiation Therapy
- Cheng-I Hsieh Division of Hematology & Oncology
- 夏和雄 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Hepatocellular Carcinoma (HCC)
Objectives
The primary objectives of the trial are:
To evaluate pharmacokinetics (PK), safety, tolerability and overall response rate (ORR) of ATG-008
in HBV+ HCC subjects who have received at least one prior line of systemic therapy.
The secondary objectives of the trial are:
To evaluate overall survival (OS)
To evaluate time to progression (TTP)
To evaluate progression-free survival (PFS)
To evaluate disease control rate (DCR)
To evaluate duration of response (DOR)
To evaluate time to response (TTR)
To evaluate survival rate
Test Drug
ATG-008
Active Ingredient
C21H27N5O3
Dosage Form
Oral tablet
Dosage
15 mg/tablet ,20 mg/tablet及30 mg/tablet
Endpoints
Primary Outcome Measures :
Cmax [ Time Frame: Day 1 - Day 15 ]
Peak Plasma Concentration (Cmax)
AUC [ Time Frame: 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 [ Time Frame: 365 DAYS ]
The treatment emergent adverse events (TEAEs) & SAE case No. in total subject No.
ORR [ Time Frame: 365 DAYS ]
Percentage of subjects with PR, or CR
Secondary Outcome Measures :
OS [ Time Frame: 365 DAYS ]
Kaplan-Meier estimate of Overall Survival
TTP [ Time Frame: 365 DAYS ]
The time from the first dose date until disease progression
PFS [ Time Frame: 365 DAYS ]
The time from the first dose date until disease progression or death from any cause
DCR [ Time Frame: 365 DAYS ]
The percentage of subjects with CR, or PR or stable disease (SD)
DOR [ Time Frame: 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 [ Time Frame: 365 DAYS ]
The time from the first dose date to the first documentation of response of PR or better.
6, 9 and 12 month of survival rate [ Time Frame: 365 DAYS ]
Percentage of patients alive
Other Outcome Measures:
Potential biomarkers in plasma and tumor tissues [ Time Frame: 365 DAYS ]
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
Additional metabolites of ATG-008 in plasma and urine [ Time Frame: Day 1 - Day 15 ]
Additional metabolites of ATG-008 in plasma and urine, and the extent of their urinary excretion/clearance
Cmax [ Time Frame: Day 1 - Day 15 ]
Peak Plasma Concentration (Cmax)
AUC [ Time Frame: 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 [ Time Frame: 365 DAYS ]
The treatment emergent adverse events (TEAEs) & SAE case No. in total subject No.
ORR [ Time Frame: 365 DAYS ]
Percentage of subjects with PR, or CR
Secondary Outcome Measures :
OS [ Time Frame: 365 DAYS ]
Kaplan-Meier estimate of Overall Survival
TTP [ Time Frame: 365 DAYS ]
The time from the first dose date until disease progression
PFS [ Time Frame: 365 DAYS ]
The time from the first dose date until disease progression or death from any cause
DCR [ Time Frame: 365 DAYS ]
The percentage of subjects with CR, or PR or stable disease (SD)
DOR [ Time Frame: 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 [ Time Frame: 365 DAYS ]
The time from the first dose date to the first documentation of response of PR or better.
6, 9 and 12 month of survival rate [ Time Frame: 365 DAYS ]
Percentage of patients alive
Other Outcome Measures:
Potential biomarkers in plasma and tumor tissues [ Time Frame: 365 DAYS ]
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
Additional metabolites of ATG-008 in plasma and urine [ Time Frame: Day 1 - Day 15 ]
Additional metabolites of ATG-008 in plasma and urine, and the extent of their urinary excretion/clearance
Inclution Criteria
Inclusion Criteria：
1. Male or female, ≥ 18 years of age at the time the ICF is signed. (Taiwan: ≥ 20 years)
2. Confirmed pathologic or radiologic diagnosis of HCC according to the American Association for the
Study of Liver Disease (AASLD) guidelines.
3. Unresectable stage B (intermediate) or C (advanced) HCC according to the Barcelona Clinic Liver
Cancer (BCLC) staging. If stage B, the subject must have progressed after, or not be eligible for,
surgical or locoregional therapy.
4. HBV+ is defined as chronic HBV infection or a history of HBV infection, based on any of the
following serologic results: HBcAb+, HBsAg+, HBV-DNA+.
5. Received at least one prior line of systemic therapy (with radiologic disease progression during or
following sorafenib and/or chemotherapy). Subjects with alternative treatments such as regorafenib
and/or anti PD-1 antibodies etc. approved by local health authorities are allowed to enter study if
they meet all other inclusion/exclusion criteria.
a. Chemotherapy includes FOLFOX (fluorouracil, leucovorin and oxaliplatin) or any other
platinum-containing regimen.
b. Chemotherapy ≥ two cycles.
6. ECOG performance status score of 0 or 1.
7. Satisfactory serum chemistry results, evidenced by the following:
a. AST (SGOT) and ALT (SGPT) ≤ 5x upper limit of normal (ULN).
b. Total bilirubin ≤ 2 × ULN.
c. Creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min.
8. Adequate bone marrow function, evidenced by the following:
a. Absolute neutrophil count (ANC) ≥ 1.5 × 109
cells/L.
b. Platelets ≥ 75 × 109
cells/L.
c. Hemoglobin ≥ 9 g/dL.
9. Child-Pugh A (score 5 or 6 only) without encephalopathy.
10. Male subjects (including those who have had a vasectomy) must agree to use a condom during
sexual intercourse with females of child-bearing potential, and shall not conceive a child starting
from the time of ICF signature, while on study medication, and for 3 months after the last dose of
study drug.
11. Female subjects of child-bearing potential must have both of the following:
a. Agree to the use of two study physician-approved contraceptive methods simultaneously,
or practice complete abstinence starting at the time of ICF signature, while on study
medication, and for 28 days following the last dose of study drug.
i. True abstinence: When this is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception.
ii. Acceptable contraceptive methods include: Oral, injectable, or implantable hormonal
contraceptive; intra-uterine device; barrier contraceptive with spermicide; or
vasectomized partner, together with at least one barrier method.
b. Have negative serum pregnancy test result at screening, confirmed by negative urine
pregnancy test within 72 hours prior to first dose of study drug (if serum test occurred >
72 hours from first dose); pregnancy test must have a sensitivity of at least 25 mIU/mL.
1. Male or female, ≥ 18 years of age at the time the ICF is signed. (Taiwan: ≥ 20 years)
2. Confirmed pathologic or radiologic diagnosis of HCC according to the American Association for the
Study of Liver Disease (AASLD) guidelines.
3. Unresectable stage B (intermediate) or C (advanced) HCC according to the Barcelona Clinic Liver
Cancer (BCLC) staging. If stage B, the subject must have progressed after, or not be eligible for,
surgical or locoregional therapy.
4. HBV+ is defined as chronic HBV infection or a history of HBV infection, based on any of the
following serologic results: HBcAb+, HBsAg+, HBV-DNA+.
5. Received at least one prior line of systemic therapy (with radiologic disease progression during or
following sorafenib and/or chemotherapy). Subjects with alternative treatments such as regorafenib
and/or anti PD-1 antibodies etc. approved by local health authorities are allowed to enter study if
they meet all other inclusion/exclusion criteria.
a. Chemotherapy includes FOLFOX (fluorouracil, leucovorin and oxaliplatin) or any other
platinum-containing regimen.
b. Chemotherapy ≥ two cycles.
6. ECOG performance status score of 0 or 1.
7. Satisfactory serum chemistry results, evidenced by the following:
a. AST (SGOT) and ALT (SGPT) ≤ 5x upper limit of normal (ULN).
b. Total bilirubin ≤ 2 × ULN.
c. Creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min.
8. Adequate bone marrow function, evidenced by the following:
a. Absolute neutrophil count (ANC) ≥ 1.5 × 109
cells/L.
b. Platelets ≥ 75 × 109
cells/L.
c. Hemoglobin ≥ 9 g/dL.
9. Child-Pugh A (score 5 or 6 only) without encephalopathy.
10. Male subjects (including those who have had a vasectomy) must agree to use a condom during
sexual intercourse with females of child-bearing potential, and shall not conceive a child starting
from the time of ICF signature, while on study medication, and for 3 months after the last dose of
study drug.
11. Female subjects of child-bearing potential must have both of the following:
a. Agree to the use of two study physician-approved contraceptive methods simultaneously,
or practice complete abstinence starting at the time of ICF signature, while on study
medication, and for 28 days following the last dose of study drug.
i. True abstinence: When this is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception.
ii. Acceptable contraceptive methods include: Oral, injectable, or implantable hormonal
contraceptive; intra-uterine device; barrier contraceptive with spermicide; or
vasectomized partner, together with at least one barrier method.
b. Have negative serum pregnancy test result at screening, confirmed by negative urine
pregnancy test within 72 hours prior to first dose of study drug (if serum test occurred >
72 hours from first dose); pregnancy test must have a sensitivity of at least 25 mIU/mL.
Exclusion Criteria
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
1. Intolerant to sorafenib/regorafenib, e.g., the subject must have discontinued either drug due to
toxicity.
2. Symptomatic central nervous system metastases. Brain Metastases that have previously been treated
and are stable for 4 weeks before the first dose date are allowed.
3. Received sorafenib/regorafenib within 14 days prior to Screening.
4. Locoregional HCC therapy (e.g., TACE, RFA), systemic chemotherapy, hormonal therapy (e.g.,
tamoxifen) or investigational therapy within 4 weeks (or 5 half-lives, whichever is shorter) prior to
Screening.
5. Tested positive for both HBV and hepatitis C virus (HCV).
a. HCV positive is defined as anti-HCV or HCV-RNA positive
6. Life expectancy of less than 3 months.
7. Prior therapy with mTOR (TORC1 and/or TORC2) inhibitors including sirolimus, temsirolimus,
everolimus, and other investigational or approved mTOR/PI3K/AKT inhibitors.
8. Major surgery or significant trauma within 28 days prior to Screening.
9. Not recovered from the acute toxic effects of prior anticancer therapy, radiation or major
surgery/significant trauma at Screening.
10. Minor surgery within 7 days prior to Screening (excluding the placement of central/peripheral lines
or skin biopsy).
11. Receiving active, ongoing treatment with systemic corticosteroids at a prednisone equivalent dose
of ≥ 10 mg daily or other systemic immune system modulators.
12. Uncontrolled diabetes, defined as HbA1c > 8%.
13. Prior organ transplant.
14. Persistent diarrhea or malabsorption ≥ National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE, Version 4.03) grade 2, despite medical management, or any
significant gastrointestinal disorder that could affect the absorption of study drug.
15. Clinically significant bleeding, especially from esophageal varices, requiring medical intervention
within 28 days prior to Screening.
16. Known history or current diagnosis of human immunodeficiency virus (HIV) infection, regardless
of treatment status.
17. Concurrent active second malignancy for which the subject is receiving therapy, excluding
non-melanomatous skin cancer, non-progressive prostate cancer treated with hormonal therapy, or
carcinoma in situ of the cervix. Any cancer curatively treated >5 years prior to entry is permitted.
18. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (e.g.,
tuberculosis) requiring antibiotic, antifungal, or antiviral therapy (other than anti-HBV therapy),
symptomatic heart failure, cardiac arrhythmia, acute or chronic pancreatitis or psychiatric
illness/social situations that would limit compliance with study requirements.
19. Significant medical conditions, laboratory abnormalities, or psychiatric illnesses that would
prevent the subject from complying fully with this protocol.
20. Any condition including the presence of laboratory abnormalities, which places subjects at
unacceptable risk should they participate in the trial.
21. Any condition that confounds the ability to interpret data from the trial.
The presence of any of the following will exclude a subject from enrollment:
1. Intolerant to sorafenib/regorafenib, e.g., the subject must have discontinued either drug due to
toxicity.
2. Symptomatic central nervous system metastases. Brain Metastases that have previously been treated
and are stable for 4 weeks before the first dose date are allowed.
3. Received sorafenib/regorafenib within 14 days prior to Screening.
4. Locoregional HCC therapy (e.g., TACE, RFA), systemic chemotherapy, hormonal therapy (e.g.,
tamoxifen) or investigational therapy within 4 weeks (or 5 half-lives, whichever is shorter) prior to
Screening.
5. Tested positive for both HBV and hepatitis C virus (HCV).
a. HCV positive is defined as anti-HCV or HCV-RNA positive
6. Life expectancy of less than 3 months.
7. Prior therapy with mTOR (TORC1 and/or TORC2) inhibitors including sirolimus, temsirolimus,
everolimus, and other investigational or approved mTOR/PI3K/AKT inhibitors.
8. Major surgery or significant trauma within 28 days prior to Screening.
9. Not recovered from the acute toxic effects of prior anticancer therapy, radiation or major
surgery/significant trauma at Screening.
10. Minor surgery within 7 days prior to Screening (excluding the placement of central/peripheral lines
or skin biopsy).
11. Receiving active, ongoing treatment with systemic corticosteroids at a prednisone equivalent dose
of ≥ 10 mg daily or other systemic immune system modulators.
12. Uncontrolled diabetes, defined as HbA1c > 8%.
13. Prior organ transplant.
14. Persistent diarrhea or malabsorption ≥ National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE, Version 4.03) grade 2, despite medical management, or any
significant gastrointestinal disorder that could affect the absorption of study drug.
15. Clinically significant bleeding, especially from esophageal varices, requiring medical intervention
within 28 days prior to Screening.
16. Known history or current diagnosis of human immunodeficiency virus (HIV) infection, regardless
of treatment status.
17. Concurrent active second malignancy for which the subject is receiving therapy, excluding
non-melanomatous skin cancer, non-progressive prostate cancer treated with hormonal therapy, or
carcinoma in situ of the cervix. Any cancer curatively treated >5 years prior to entry is permitted.
18. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (e.g.,
tuberculosis) requiring antibiotic, antifungal, or antiviral therapy (other than anti-HBV therapy),
symptomatic heart failure, cardiac arrhythmia, acute or chronic pancreatitis or psychiatric
illness/social situations that would limit compliance with study requirements.
19. Significant medical conditions, laboratory abnormalities, or psychiatric illnesses that would
prevent the subject from complying fully with this protocol.
20. Any condition including the presence of laboratory abnormalities, which places subjects at
unacceptable risk should they participate in the trial.
21. Any condition that confounds the ability to interpret data from the trial.
The Estimated Number of Participants
-
Taiwan
50 participants
-
Global
126 participants
