Second-line Treatment With CAdonilimab and LEnvatinib for Unresectable HCC

NCT06361758 | Withdrawn Phase 2 DMC

• 1 other identifier: B2023-326(2)
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Hepatocellular Carcinoma

Keywords

cadonilimab (anti PD-1/CTLA-4 bispecific antibody)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Objective Response Rate (ORR) per mRECIST

  Up to two years

• Disease control Rate (DCR)

  Up to two years

• Duration of response (DoR)

  Up to two years

• Progression-Free-Survival (PFS)

  Up to two years

• Overall survival Overall survival (OS)

  Up to three years

Study Arms (1)

Cadonilimab+Lenvatinib

EXPERIMENTAL

Drug: Cadonilimab+Lenvatinib

Interventions

Cadonilimab+Lenvatinib DRUG

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 Eligible patients will receive AK104 plus Lenvatinib until disease progression or withdrawn ICF or death, whichever comes first.

Cadonilimab+Lenvatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Sun Yat-sen University: collaborator
• Eastern Hepatobiliary Surgery Hospital: collaborator

Study Sites (3)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Sun Yat-sen University Cancer Center)

Guangzhou, China

Location

Eastern Hepatobiliary Surgery Hospital

Shanghai, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Huichuan Sun

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 12, 2024
• Study Start: May 31, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)