A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Plus Lenvatinib in First-line Advanced Hepatocellular Carcinoma
- Registration Number
- NCT04444167
- Lead Sponsor
- Akeso
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 59
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AK104 and Lenvatinib AK104 AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight\<60kg,PO QD AK104 and Lenvatinib Lenvatinib AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight\<60kg,PO QD
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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
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.
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.
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).
Trial Locations
- Locations (1)
Chinese PLA General Hospital
🇨🇳Beijing, Beijing, China