Second-line Treatment With CAdonilimab and LEnvatinib for Unresectable HCC

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Cadonilimab+Lenvatinib

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangzhou, China
    • Sun Yat-sen University Cancer Center)
  • Shanghai, China
    • Eastern Hepatobiliary Surgery Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadonilimab+Lenvatinib	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Overall survival Overall survival (OS)	Defined as the time between the first dose to death due to any causes.	Up to three years
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

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Sun Yat-sen University; Eastern Hepatobiliary Surgery Hospital
• Investigators: Principal Investigator: Huichuan Sun, Study Principal Investigator

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: cadonilimab (anti PD-1/CTLA-4 bispecific antibody)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: B2023-326(2)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No