A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Plus Lenvatinib in First-line Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

An Open-Label Multi-Center Phase Ib/II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in Combination With Lenvatinib As the First-Line Therapy for Patients With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04444167
• Other study ID #: AK104-206
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 7, 2020
• Est. completion date: November 20, 2023

Study information

• Verified date: April 2024
• Source: Akeso
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: November 20, 2023
• Est. primary completion date: November 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• AK104
Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months

Drug:
• Lenvatinib
Subjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Akeso	Akeso Pharmaceuticals, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	the time of informed consent signed through 90 days after the last dose of AK104 and
Secondary	Observed concentrations of AK104	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.	From first dose of AK104 through 90 days after last dose of AK104
Secondary	Number of subjects who develop detectable anti-drug antibodies (ADAs)	The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).	From first dose of AK104 through 90 days after last dose of AK104