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

July 6, 2023 updated by: Antengene Therapeutics Limited

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
73

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cmax
Time Frame: Day 1 - Day 15
Peak Plasma Concentration (Cmax)
Day 1 - Day 15
AUC
Time Frame: Day 1 - Day 15
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
Time Frame: 365 DAYS
The treatment emergent adverse events (TEAEs) & SAE case No. in total subject No.
365 DAYS
ORR
Time Frame: 365 DAYS
Percentage of subjects with PR, or CR
365 DAYS

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
OS
Time Frame: 365 DAYS
Kaplan-Meier estimate of Overall Survival
365 DAYS
TTP
Time Frame: 365 DAYS
The time from the first dose date until disease progression
365 DAYS
PFS
Time Frame: 365 DAYS
The time from the first dose date until disease progression or death from any cause
365 DAYS
DCR
Time Frame: 365 DAYS
The percentage of subjects with CR, or PR or stable disease (SD)
365 DAYS
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
365 DAYS
TTR
Time Frame: 365 DAYS
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
Time Frame: 365 DAYS
Percentage of patients alive
365 DAYS

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
365 DAYS
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
Day 1 - Day 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Antengene Therapeutics Limited

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Stephen Xie, PhD, Medical Monitor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 7, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 3, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 3, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 20, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 19, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 10, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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