Ligufalimab and Cadonilimab in Advanced Liver Cancers

NCT06789848 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SCCC-15224; STU-2024-1210
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to find out if the combination of Ligufalimab and Cadonilimab are effective in treating advanced hepatobiliary cancers that have failed prior therapy.

Conditions

Refractory Hepatocellular Carcinoma; Biliary Tract Cancer; Advanced Hepatocellular Carcinoma

Keywords

liver; other digestive organs

Outcome Measures

Primary Outcomes (1)

• Objective Response rate of combination ligufalimab and cadonilimab

  To determine the best objective response rate assessed by RECIST guidelines (version 1.1) of combination ligufalimab and cadonilimab in patients with advanced hepatobiliary cancers previously exposed to anti-PD-1/L1 antibody treatments.

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

Secondary Outcomes (4)

• Overall survival of combination ligufalimab and cadonilimab

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

• Progression-free survival of combination ligufalimab and cadonilimab

  udy treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

• Duration of response of combination ligufalimab and cadonilimab

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

• Overall safety profile of combination ligufalimab and cadonilimab.

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

Study Arms (2)

Cohort A: Hepatocellular carcinoma (HCC) / Liver Cancer

EXPERIMENTAL

Ligufalimab and Cadonilimab are given via intravenous (through the veins) infusion in the clinic. Each clinic visit will last 4-5 hours. Infusions of study drugs will be given on the first day of every 21-day cycle. Study medications will continue if evaluations show that disease has not gotten worse.

Drug: Ligufalimab; Drug: Cadonilimab

Cohort B: Bile duct cancer

EXPERIMENTAL

Ligufalimab and Cadonilimab are given via intravenous (through the veins) infusion in the clinic. Each clinic visit will last 4-5 hours. Infusions of study drugs will be given on the first day of every 21-day cycle. Study medications will continue if evaluations show that disease has not gotten worse.

Drug: Ligufalimab; Drug: Cadonilimab

Interventions

Ligufalimab DRUG

Ligufalimab (AK117) 45 mg/kg IV over 120 minutes on Day 1 every 3 weeks

Cohort A: Hepatocellular carcinoma (HCC) / Liver Cancer; Cohort B: Bile duct cancer

Cadonilimab DRUG

Cadonilimab (AK104) 10 mg/kg IV over 60 minuets at least 30 minutes after Ligufalimab on Day 1 every 3 weeks

Cohort A: Hepatocellular carcinoma (HCC) / Liver Cancer; Cohort B: Bile duct cancer

Eligibility Criteria

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

You may qualify if:

• Histological confirmation of specific disease -Cohort A (HCC): Patient must have a diagnosis confirmed by histology or clinically by the American Association for the Study of Liver Diseases (AASLD) criteria in patients with cirrhosis. Known fibrolamellar HCC will be excluded.
• Cohort B (BTC, biliary tract cancers): Patients must have histologically confirmed biliary tract cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancers). Patients with combined HCC-cholangiocarcinoma may be enrolled in Cohort B.
• Locally advanced or metastatic disease
• Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
• Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).
• Refractory to or relapsed after prior anti-PD-1/L1 antibody therapy. May have received anti-PD-1/L1 monotherapy or combination therapy as any line of therapy including in the neoadjuvant or adjuvant setting. Patients who discontinued prior immune checkpoint inhibitor treatment due to a high-grade toxicity (Grade 4) are not eligible.
• For patients in cohort A who do not have a clinical diagnosis of HCC according to the AASLD criteria, formalin-fixed, paraffin-embedded (FFPE) tumor diagnostic tissue samples must have been obtained within 4 years from the time of consent. Baseline tissue will be requested any time after consent. It is strongly recommended that tissue is obtained from standard-of-care biopsies confirming progression of disease on prior therapy so that the patient has not received any intervening systemic anti-cancer treatment from the time that the baseline tissue was obtained.
• Prior locoregional therapy is allowed provided the following are met: 1) at least 2 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation; 2) target lesion has increased in size ≥25% since the cessation of locoregional therapy or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion and radiotherapy will be completed at least 2 weeks prior to study drug administration.
• Age ≥ 18 years
• Child-Pugh Score A or B7 (only applicable for Cohort A)
• ECOG Performance score of 0-1
• Adequate organ and marrow function (without chronic, ongoing growth factor support or transfusion in the last 2 weeks) as defined below:
• Platelet count ≥ 50,000/mm3
• Hgb ≥ 9 g/dl
• Absolute neutrophil ≥ 1,000 cells/mm3

You may not qualify if:

• Prior liver transplant.
• Known human immunodeficiency virus (HIV) positive (testing not required).
• Use of any live vaccines against infectious diseases within 28 days of first dose of study drug administration.
• History of trauma or major surgery within 28 days prior to the first dose of study drug administration. (Tumor biopsy or placement of central venous access catheter (eg, port or similar) is not considered a major surgical procedure).
• Underlying medical conditions that, in the investigator's opinion, will make the administration of study drugs hazardous, including but not limited to:
• Interstitial lung disease, including history of interstitial lung disease or non infectious pneumonitis (lymphangitic spread of cancer is not disqualifying),
• Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of study drugs,
• Clinically significant cardiovascular disease,
• A condition that may obscure the interpretation of toxicity determination or AEs,
• History of prior solid-organ transplantation.
• Hypersensitivity to IV contrast; not suitable for pre-medication.
• Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
• Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study.
• Known history of active bacillus tuberculosis.

Sponsors & Collaborators

• Josephine Hughes Sterling Foundation: collaborator
• University of Texas Southwestern Medical Center: lead
• Akesobio: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Biliary Tract Neoplasms

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; Biliary Tract Diseases

Study Officials

• David Hsieh, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carrie Manwaring

CONTACT

214-648-7097; Carrie.Manwaring@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Internal Medicine

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: January 23, 2025
• Study Start: February 18, 2025
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2030
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)