Clinical trial NCT04444167: A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Plus Lenvatinib in First-line Advanced Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: VEGF
Anti-PD-1
Tyrosine Kinase Inhibitor (TKI)
Anti-CTLA-4
Lead sponsor: Akeso
Sponsor class: INDUSTRY
Collaborators: name: Akeso Pharmaceuticals, Inc.
First posted: 2020-06-23
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Duration of response (DoR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Number of participants with adverse events (AEs)
timeFrame: the time of informed consent signed through 90 days after the last dose of AK104 and
measure: Observed concentrations of AK104
timeFrame: From first dose of AK104 through 90 days after last dose of AK104
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of AK104 through 90 days after last dose of AK104
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Li Bai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA General Hospital
name: Shunchang Jiao, MD
role: PRINCIPAL_INVESTIGATOR
References: