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

Trial Summary

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.

What data supports the effectiveness of the drug Cadonilimab for liver cancer?

Research shows that Cadonilimab, when combined with another drug called lenvatinib, has been studied for treating advanced liver cancer, showing potential benefits. Additionally, Cadonilimab has shown antitumor activity in other advanced cancers, suggesting it might be effective for liver cancer as well. ^{1 2 3 4 5}

Is the combination of Ligufalimab and Cadonilimab safe for humans?

Cadonilimab, used alone or with other treatments, has been generally well tolerated in studies for various cancers, with common side effects being mild infusion-related reactions. However, there is a potential risk for serious skin reactions, as seen in a case of toxic epidermal necrolysis (a severe skin condition), which was successfully treated with another medication. ^{1 4 5 6 7}

What makes the drug Ligufalimab + Cadonilimab unique for liver cancer?

The drug Ligufalimab + Cadonilimab is unique because it combines two components: Ligufalimab and Cadonilimab, a bispecific antibody that targets both PD-1 and CTLA-4 proteins, potentially enhancing the immune system's ability to fight liver cancer more effectively than treatments targeting these proteins individually. ^{1 4 5 6 8}

What is the purpose of this trial?

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.

Research Team

David Hsieh, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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, 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]

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]

References

1. Switzerland 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. [2023]

2. New Zealand 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. [2020]

4. England 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. [2023]

5. Ireland 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). [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Cadonilimab-related toxic epidermal necrolysis-like reactions successfully treated with supplemental Adalimumab. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Cadonilimab: First Approval. [2022]