Back to resultsA Study of Anti-PD-1/CTLA-4 Bispecific AK104 Alone or in Combination With Lenvatinib in Advanced Hepatocellular Carcinoma
Primary Purpose
Hepatocellular Carcinoma
Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
AK104 lenvatinib
AK104
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Anti-PD-1, Anti-CTLA-4, Bispecific
Eligibility Criteria
Inclusion Criteria:
- Signed written informed consent form voluntarily.
- Histologically or cytologically documented hepatocellular carcinoma.
- BCLC stage C, and non-resectable BCLC stage B .
- At least one measurable lesion according to RECIST criteria.
- ECOG of 0 or 1.
- Adequate organ function.
- Estimated life expectancy of ≥3 months.
- For women of childbearing potential: agreement to remain abstinent; For men: agreement to remain abstinent
Exclusion Criteria:
- Histologically or cytologically documented fibrolamellar hepatocellular carcinoma, sarcoma-like hepatocellular carcinoma, cholangiocarcinoma, etc.
- History of hepatic encephalopathy or liver transplantation.
- Clinical significance of hydrothorax, ascites or pericardial effusion.
- Central nervous system metastases and/or carcinomatous meningitis.
- Any risk of bleeding; severe bleeding tendency or coagulation dysfunction, or under thrombolytic therapy.
- Occurred arteriovenous thromboembolic events within 6 months before the first administration.
- Tumor volume > 50% liver volume; portal vein tumor thrombus or inferior vena cava tumor thrombus.
- Inadequately controlled arterial hypertension.
- Attack of symptomatic congestive heart failure (LVEF<50%); History of congenital long QT syndrome.
- Known presence or history of interstitial lung disease or required hormone treatment interstitial lung disease.
- Severe infections.
- Receipt of any anti-tumor treatment, chemotherapy, targeted therapy, immunotherapy,
- Enrollment of another clinical study within 4 weeks prior to the first administration of study drugs.
- Unable to receive an enhanced CT or MRI scan of the liver.
Sites / Locations
- The first affilited hospital zhejiang university school of medcine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
AK104
AK104 and Lenvatinib
Arm Description
AK104 15mg/kg IV every 3weeks (Q3W)
AK104 15 mg/kg IV every 3 weeks (Q3W) Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD
Outcomes
Primary Outcome Measures
Objective response rate (ORR)
ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.
Secondary Outcome Measures
Disease control rate (DCR)
The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
Duration of response (DoR)
Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first
Progression-free survival (PFS)
Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first
Number of participants with adverse events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment
Full Information
NCT ID
NCT04728321
First Posted
January 24, 2021
Last Updated
October 17, 2022
Sponsor
Akeso
Collaborators
Akeso Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04728321
Brief Title
A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Alone or in Combination With Lenvatinib in Advanced Hepatocellular Carcinoma
Official Title
An Open-Label Multi-Center Phase II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 Alone or in Combination With Lenvatinib in Patients With Advanced Hepatocellular Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 27, 2021 (Actual)
Primary Completion Date
March 30, 2022 (Actual)
Study Completion Date
March 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akeso
Collaborators
Akeso Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
An open-label multi-center phase II study to evaluate the efficacy and safety of anti-PD-1/CTLA-4 bispecific antibody AK104 alone or in combination with lenvatinib in patients with advanced hepatocellular carcinoma.
Detailed Description
This is a multi-center, multi-cohort, open-label phase 2 clinical study to evaluate the anti-tumor activity, safety, PK profile, immunogenicity and potential biomarkers of AK104 alone or in combination with for the treatment of advanced hepatocellular carcinoma
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Anti-PD-1, Anti-CTLA-4, Bispecific
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AK104
Arm Type
Experimental
Arm Description
AK104 15mg/kg IV every 3weeks (Q3W)
Arm Title
AK104 and Lenvatinib
Arm Type
Experimental
Arm Description
AK104 15 mg/kg IV every 3 weeks (Q3W) Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD
Intervention Type
Biological
Intervention Name(s)
AK104 lenvatinib
Intervention Description
Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months
Intervention Type
Biological
Intervention Name(s)
AK104
Intervention Description
Subjects will receive AK104 until disease progression or for a maximum of 24 months
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Disease control rate (DCR)
Description
The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
Time Frame
Up to 2 years
Title
Duration of response (DoR)
Description
Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first
Time Frame
Up to 2 years
Title
Progression-free survival (PFS)
Description
Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first
Time Frame
Up to 2 years
Title
Number of participants with adverse events (AEs)
Description
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment
Time Frame
the time of informed consent signed through 90 days after the last dose of AK104 and Lenvatinib
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed written informed consent form voluntarily.
Histologically or cytologically documented hepatocellular carcinoma.
BCLC stage C, and non-resectable BCLC stage B .
At least one measurable lesion according to RECIST criteria.
ECOG of 0 or 1.
Adequate organ function.
Estimated life expectancy of ≥3 months.
For women of childbearing potential: agreement to remain abstinent; For men: agreement to remain abstinent
Exclusion Criteria:
Histologically or cytologically documented fibrolamellar hepatocellular carcinoma, sarcoma-like hepatocellular carcinoma, cholangiocarcinoma, etc.
History of hepatic encephalopathy or liver transplantation.
Clinical significance of hydrothorax, ascites or pericardial effusion.
Central nervous system metastases and/or carcinomatous meningitis.
Any risk of bleeding; severe bleeding tendency or coagulation dysfunction, or under thrombolytic therapy.
Occurred arteriovenous thromboembolic events within 6 months before the first administration.
Tumor volume > 50% liver volume; portal vein tumor thrombus or inferior vena cava tumor thrombus.
Inadequately controlled arterial hypertension.
Attack of symptomatic congestive heart failure (LVEF<50%); History of congenital long QT syndrome.
Known presence or history of interstitial lung disease or required hormone treatment interstitial lung disease.
Severe infections.
Receipt of any anti-tumor treatment, chemotherapy, targeted therapy, immunotherapy,
Enrollment of another clinical study within 4 weeks prior to the first administration of study drugs.
Unable to receive an enhanced CT or MRI scan of the liver.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tingbo Liang, MD
Organizational Affiliation
The First Affiliated Hospital Zhejiang University School of Medcine
Official's Role
Principal Investigator
Facility Information:
Facility Name
The first affilited hospital zhejiang university school of medcine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
12. IPD Sharing Statement
Learn more about this trial
A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Alone or in Combination With Lenvatinib in Advanced Hepatocellular Carcinoma
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