Ligufalimab + Cadonilimab for Liver Cancer

Overseen By Carrie Manwaring

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Antivirals

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Liver transplant, HIV, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

Duration: Up to 24 months

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, Ligufalimab and Cadonilimab, to determine their effectiveness in treating advanced liver and bile duct cancers unresponsive to previous treatments. Participants receive these medications through an IV every three weeks at a clinic. Suitable candidates for this trial include those with advanced liver or bile duct cancer that has not improved with other treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants cannot be on certain treatments like systemic corticosteroids above a specific dose or other immunosuppressive medications within 14 days of starting the study drugs. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of Ligufalimab and Cadonilimab is being tested for safety and effectiveness in treating advanced liver and bile duct cancers. Previous patients have demonstrated that these two drugs together may help the immune system better recognize and attack cancer cells.

Other clinical trials suggest that this combination has led to better results than standard treatments. Although detailed safety data is not available here, the study is at a stage where treatments are usually well-tolerated, meaning serious side effects are less common, though some mild to moderate side effects might still occur.

Cadonilimab has also shown promise in treating other types of cancer, indicating it is generally safe for humans. Prospective participants should consult a healthcare provider about possible side effects and safety before joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Ligufalimab and Cadonilimab because, unlike traditional treatments for liver cancer, such as surgery, radiation, or chemotherapy, these drugs are designed to work with your immune system. Cadonilimab is a bispecific antibody that targets both PD-1 and CTLA-4 pathways, potentially enhancing the immune response against cancer cells. Ligufalimab targets the TIGIT pathway, another immune checkpoint, which may further boost the body’s ability to fight the tumor. By combining these mechanisms, these treatments offer a novel approach that could improve outcomes for patients by potentially controlling the cancer more effectively and with fewer side effects than current options.

What evidence suggests that this trial's treatments could be effective for liver cancer?

In this trial, participants will receive a combination of Ligufalimab and Cadonilimab. Research has shown that using these drugs together may enhance the immune system's ability to identify and destroy cancer cells. Studies have found that combinations with Cadonilimab are promising in overcoming the body's resistance to fighting various tumors. When used together, these drugs have produced better results than standard treatments. Additionally, Cadonilimab has demonstrated effectiveness against other advanced cancers, suggesting potential for liver cancer treatment as well. Overall, early results are promising for treating advanced liver and bile duct cancers with this combination. ^{1 3 4 5 6}

Who Is on the Research Team?

David Hsieh, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with advanced liver or biliary tract cancers, including hepatocellular carcinoma and skin cancer of the liver area, who have not responded to previous treatments. Specific eligibility details are not provided.

Inclusion Criteria

Ability to understand and sign a written informed consent

Willingness and ability to comply with protocol requirements and restrictions

My cancer is a type of biliary tract cancer.

Exclusion Criteria

I have not received any live vaccines in the last 28 days.

I haven't had cancer treatment in the last 2 years, except for treatable local cancers.

Pregnant or nursing women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ligufalimab and Cadonilimab via intravenous infusion every 21 days

Up to 24 months

Infusions on the first day of every 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cadonilimab
• Ligufalimab

Trial Overview The effectiveness of combining two drugs, Ligufalimab and Cadonilimab, is being tested on patients with certain types of advanced liver cancers that haven't improved after prior therapy.

How Is the Trial Designed?

Group I: Cohort B: Bile duct cancer Experimental Treatment 2 Interventions

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.

Group II: Cohort A: Hepatocellular carcinoma (HCC) / Liver Cancer Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Akesobio

Industry Sponsor

Trials

4

Recruited

200+

Akesobio

Collaborator

Trials

4

Recruited

200+

Josephine Hughes Sterling Foundation

Collaborator

Trials

1

Recruited

60+

Published Research Related to This Trial

Cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, was found to be well tolerated in a phase 1 study with 119 participants, establishing a recommended dose of 6 mg/kg every two weeks and showing only one dose-limiting toxicity event.

The treatment demonstrated promising efficacy with a confirmed overall response rate of 13.4% and a median duration of response of 12.9 months in patients with advanced solid tumors, despite a notable incidence of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors. Frentzas, S., Gan, HK., Cosman, R., et al.[2023]

Cadonilimab, a bi-specific antibody approved for certain cancers, has been associated with a rare case of toxic epidermal necrolysis (TEN) during treatment for hepatocellular carcinoma, highlighting a potential safety concern.

The patient's TEN-like reaction was successfully managed with supplemental Adalimumab, suggesting that this treatment could be an effective option for addressing Cadonilimab-related adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Cadonilimab-related toxic epidermal necrolysis-like reactions successfully treated with supplemental Adalimumab. Chen, PY., Li, ZY., Cai, SQ.[2023]

In a study involving 59 patients with advanced hepatocellular carcinoma, the combination of cadonilimab and lenvatinib showed an objective response rate of approximately 35.5% to 35.7%, with a median duration of response around 13.6 months, indicating promising efficacy as a first-line treatment.

While the treatment was effective, it also had a significant safety profile, with 66.1% of patients experiencing grade ≥ 3 treatment-related adverse events, including common issues like decreased platelet count and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial. Qiao, Q., Han, C., Ye, S., et al.[2023]

Cadonilimab, a bispecific PD-1/CTLA-4 antibody, demonstrated a manageable safety profile with 28% of patients experiencing grade 3-4 treatment-related adverse events, indicating it can be safely administered to patients with advanced solid tumors.

In a phase 2 trial, cadonilimab showed promising antitumor activity, with an objective response rate of 32.3% in cervical cancer patients, suggesting its potential effectiveness in treating advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Gao, X., Xu, N., Li, Z., et al.[2023]

In a phase 1b study involving 223 patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab resulted in a significantly longer median progression-free survival of 5.6 months compared to 3.4 months for atezolizumab alone, indicating enhanced efficacy of the combination treatment.

The most common serious treatment-related adverse events included hypertension and proteinuria, with a treatment-related death rate of 3% in the combination group, suggesting that while the combination therapy is effective, it does carry some safety risks that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lee, MS., Ryoo, BY., Hsu, CH., et al.[2020]

The combination of a PD-1 inhibitor and regorafenib as second-line treatment for advanced hepatocellular carcinoma (HCC) showed a higher objective response rate (39.5% vs 15.6%) and longer overall survival (median 14.5 months vs 9.5 months) compared to regorafenib alone, based on a study of 38 patients.

The safety profile of the combination therapy was comparable to regorafenib alone, with no significant difference in the incidence of severe adverse events (36.8% vs 28.1%), indicating that this combination is both effective and safe for patients with unresectable HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety of an Immune Checkpoint Inhibitor in Combination with Regorafenib Therapy as Second-Line Regimen for Patients with Unresectable Hepatocellular Carcinoma. Li, J., Jia, Y., Shao, C., et al.[2023]

Cadonilimab, an anti PD-1 and CTLA-4 bispecific antibody, showed limited efficacy in treating previously treated metastatic non-small-cell lung cancer (NSCLC), achieving an objective response rate of only 10% in patients who were immunotherapy naïve after platinum-based chemotherapy.

The treatment was well-tolerated, with only 11.3% of patients experiencing grade 3-4 adverse events, suggesting that cadonilimab could be a viable option for second-line therapy in NSCLC, particularly for those who have not previously received immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study). Zhao, Y., Ma, Y., Fan, Y., et al.[2023]

Cadonilimab is a bi-specific antibody targeting PD-1 and CTLA-4, developed for treating various solid tumors, and was approved in China in June 2022 specifically for patients with relapsed or metastatic cervical cancer who have not responded to platinum-based chemotherapy.

The approval of cadonilimab marks a significant milestone in cancer treatment, providing a new therapeutic option for patients with advanced cervical cancer after standard chemotherapy has failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cadonilimab: First Approval. Keam, SJ.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06789848

Ligufalimab and Cadonilimab in Advanced Liver Cancers Study Overview. The goal of this clinical trial is to find out if the combination of Ligufalimab and Cadonilimab are effective in treating advanced ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-01329

Ligufalimab and Cadonilimab for the Treatment of ... This phase II trial studies how well ligufalimab and cadonilimab work in treating patients with hepatobiliary cancers that may have spread from where it ...

3. akesobio.com akesobio.com/en/media/akeso-news/240906/

Akeso to Present Data from 13 Clinical Studies at ESMO ... When combined with ligufalimab (CD47), the clinical outcome improved further, surpassing current standard treatments. These findings highlight ...

4. prnewswire.com prnewswire.com/news-releases/akeso-to-present-data-from-13-clinical-studies-at-esmo-2024-featuring-its-internally-developed-cadonilimab-ivonescimab-ligufalimab-and-other-io-antibodies-302240123.html

Akeso to Present Data from 13 Clinical Studies at ESMO ... When combined with ligufalimab (CD47), the clinical outcome improved further, surpassing current standard treatments. These findings highlight ...

5. withpower.com withpower.com/trial/ligufalimab-cadonilimab-for-liver-cancer-3c748

Ligufalimab + Cadonilimab for Liver Cancer Additionally, Cadonilimab has shown antitumor activity in other advanced cancers, suggesting it might be effective for liver cancer as well.

6. cancer.gov cancer.gov/clinicaltrials/NCI-2025-01329

Ligufalimab and Cadonilimab for the Treatment of ... Administering these medications together may cause the immune system to recognize and kill tumor cells more effectively than if one drug was used by itself.