Second-line Treatment With CAdonilimab and LEnvatinib for Unresectable HCC

Hepatocellular Carcinoma Clinical Trial

Official title:

Second-line Treatment With CAdonilimab and LEnvatinib for Unresectable HCC: A Single Arm, Multicenter, Phase II Trial. (SCALE)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06361758
• Other study ID #: B2023-326(2)
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 31, 2024
• Est. completion date: May 31, 2027

Study information

• Verified date: April 2024
• Source: Shanghai Zhongshan Hospital
• Contact: Huichuan Sun
• Phone: +86-21-64041990
• Email: sun.huichuan[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multi-center, single-arm, phase II study to evaluate the efficacy and safety of lenvatinib in combination with cadonilimab as second-line therapy in subjects with advanced hepatocellular carcinoma (HCC) who failed first-line standard therapy of immunotheray and antiangiogenic therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Sign a written informed consent and be able to comply with the visit and related procedures required by the study protocol
• Age 18-75 years old, Male of Female
• ECOG PS 0-1
• histologically/cytologically or clinically (according to Chinese guidelines for primary liver cancer diagnosis and treatment (2022) criteria) confirmed initial diagnosis of HCC
• Not suitable for radical surgery and/or local treatment, BCLC stage C or stage B who failed local treatment
• Patients who progressed on first-line standard system therapy (Atezolizumab plus bevacizumab, sintilimab combined with bevacizumab, or Camrelizumab and Apatinib, only these three regimenes) or with intolerable toxicity ( except for immunotherapy intolerance)
• Child Pugh A-B7
• Expected survival time=12 weeks
• At least one measurable lesion (RECIST 1.1)
• Enough organ and bone marrow function

Exclusion Criteria:

• Fibrolamellar sarcomatoid or mixed cholangiocarcinoma-hepatocellular carcinoma.
• Other anti-tumor therapies have been received after first-line systemic anti-tumor therapy.
• Have history of hepatic encephalopathy, or a history of liver transplantation.
• There are clinical symptoms requiring drainage of pleural fluid, ascites, pericardial effusion.
• People with acute or chronic active hepatitis B or hepatitis C, hepatitis B virus (HBV) DNA > 2000IU/ml or 10^4 copies /ml; Hepatitis C virus (HCV) RNA > 10^3 copies /ml; Hepatitis B surface antigen (HbsAg) and anti-HCV antibodies were both positive.
• Central nervous system metastasis.
• Previous bleeding from esophageal or fundus varices due to portal hypertension occurred within 6 months.
• Autoimmune immune disease.
• HIV infection.
• Pregnant women.
• The presence of any serious or uncontrolled systemic disease.
• Other acute or chronic diseases, psychiatric disorders or abnormal laboratory test values that may lead to the following results: increasing the risk associated with research or drug administration, or interfering with the interpretation of research results. The Investigator considers that there are other potential risks that are not suitable for participation in the study.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Cadonilimab+Lenvatinib
Cadonilimab (AK104): 15mg/kg Q3W iv D1 + Lenvatinib: 8 mg (body weight <60 kg) or 12mg (body weight =60 kg) orally QD. Eligible patients will receive AK104 plus Lenvatinib until disease progression or withdrawn ICF or death, whichever comes first.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center)	Guangzhou
China	Eastern Hepatobiliary Surgery Hospital	Shanghai
China	Zhongshan Hospital, Fudan University	Shanghai	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital	Eastern Hepatobiliary Surgery Hospital, Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) per RECIST v1.1	Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.	Up to two years
Secondary	Objective Response Rate (ORR) per mRECIST	Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to mRECIST.	Up to two years
Secondary	Disease control Rate (DCR)	Defined as the proportion of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) according to RECIST v1.1 and mRECIST respectively.	Up to two years
Secondary	Duration of response (DoR)	Defined as the time from the first dose to disease progression or death in patients who achieve complete or partial response.	Up to two years
Secondary	Progression-Free-Survival (PFS)	Defined as the time between signing the informed consent form to the disease progression (according to RECIST v1.1 criteria) or death due to any cause.	Up to two years
Secondary	Overall survival Overall survival (OS)	Defined as the time between the first dose to death due to any causes.	Up to three years
Secondary	Incidence of Adverse Events	Adverse events (AEs) ; serious adverse events (SAEs); Treatment related Adverse events (TRAEs); Use NCI-CTCAE version 5.0 for classification and grading.	Up to two years