Hepatocellular Carcinoma
Conditions
Keywords
VEGF, Anti-PD-1, Tyrosine Kinase Inhibitor (TKI), Anti-CTLA-4
Brief summary
An open-label multi-center phase Ib/II study to evaluate the efficacy and safety of anti-PD-1/CTLA-4 bispecific antibody AK104 plus lenvatinib as the first-line therapy for patients with advanced hepatocellular carcinoma.
Detailed description
This is a multi-center, multi-cohort, open-label phase 1b/2 clinical study to evaluate the anti-tumor activity, safety, PK profile, immunogenicity and potential biomarkers of AK104 plus lenvatinib for the treatment of advanced hepatocellular carcinoma.
Interventions
BIOLOGICALAK104
Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months
DRUGLenvatinib
Subjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months
Sponsors
Akeso Pharmaceuticals, Inc.
Akeso
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 2 years | ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) | Up to 2 years | 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) | Up to 2 years | 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. |
| Disease control rate (DCR) | Up to 2 years | 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. |
| Observed concentrations of AK104 | From first dose of AK104 through 90 days after last dose of AK104 | The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration. |
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | From first dose of AK104 through 90 days after last dose of AK104 | The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs). |
| Number of participants with adverse events (AEs) | the time of informed consent signed through 90 days after the last dose of AK104 and | 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. |
Countries
China
Outcome results
None listed