Domvanalimab + Zimberelimab 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, Immunosuppressives

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: Unknown

Duration: up to 24 months

58 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn about advanced liver and bile duct cancers. The main question it aims to answer is: If the combination of Domvanalimab and Zimberelimab are effective in treating advanced hepatobiliary cancers that have failed prior treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antiviral therapy for hepatitis B, you should continue it throughout the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Domvanalimab + Zimberelimab for liver cancer?

While there is no direct data on Domvanalimab + Zimberelimab for liver cancer, similar immunotherapy combinations like durvalumab-tremelimumab have shown promise in treating advanced liver cancer, suggesting potential effectiveness. ^{1 2 3 4 5}

Research Team

David Hsieh, MD

Principal Investigator

Assistant Professor

Eligibility Criteria

This trial is for adults with advanced liver or bile duct cancer that's not suitable for surgery or has come back after treatment. They must have tried anti-PD-1/L1 therapy before, be in fairly good health (ECOG score 0-1), and have a certain level of liver function (Child-Pugh Score A/B7-B8). Pregnant women, HIV-positive individuals, those with recent major surgeries or trauma, autoimmune diseases requiring treatment within the past two years, severe allergies to monoclonal antibodies, active infections like tuberculosis, and anyone on high-dose steroids can't join.

Inclusion Criteria

I had treatment targeting a specific area of my cancer and met all required conditions.

My cancer can be measured by scans.

My diagnosis is liver or bile duct cancer, but not fibrolamellar HCC or combined HCC-cholangiocarcinoma.

Exclusion Criteria

Underlying medical conditions that, in the investigator's opinion, will make the administration of study drugs hazardous

I do not have dementia or any mental condition that affects my ability to consent.

I have not had any autoimmune diseases requiring systemic treatment in the past 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Zimberelimab (AB122) 360 mg IV and Domvanalimab (AB154) 1200 mg IV every three weeks until disease progression, unacceptable toxicity, or other discontinuation criteria

up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Domvanalimab
• Zimberelimab

Trial Overview The study tests if Domvanalimab combined with Zimberelimab helps treat advanced hepatobiliary cancers that haven't responded to previous treatments. Participants will receive both drugs and their effectiveness against these types of cancers will be evaluated.

Participant Groups

Group I: Zimberelimab and Domvanalimab Experimental Treatment 2 Interventions

Individual will be given Zimberelimab (AB122) 360 mg IV in a 1 hour infusion + 30 minute rest + Domvanalimab (AB154) 1200 mg IV in a 1 hour infusion every three weeks. Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

Arcus Biosciences, Inc.

Industry Sponsor

Trials

44

Recruited

7,500+

Findings from Research

The combination of tremelimumab and durvalumab (T300 + D) showed the highest overall survival rate (18.7 months) and objective response rate (24.0%) among patients with unresectable hepatocellular carcinoma, indicating its potential as an effective treatment option.

All treatment regimens were generally well-tolerated, but T300 + D had the most favorable safety profile, with a significant association between early CD8+ lymphocyte expansion and treatment response, suggesting a promising mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. Kelley, RK., Sangro, B., Harris, W., et al.[2022]

In a study of patients with hepatocellular carcinoma (HCC) treated with the checkpoint inhibitor tremelimumab, there was a notable increase in various activated T cell populations, indicating a robust immune response.

Patients with higher baseline levels of CD4+PD-1+ T cells were more likely to respond positively to tremelimumab therapy, suggesting this could serve as a potential biomarker for predicting treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of anti-CTLA4 treatment on peripheral and intra-tumoral T cells in patients with hepatocellular carcinoma. Agdashian, D., ElGindi, M., Xie, C., et al.[2023]

In a phase 2 study involving 41 patients with previously treated advanced hepatocellular carcinoma (HCC), the combination of serplulimab and HLX04 demonstrated a manageable safety profile, with 70% of patients in one group experiencing grade ≥3 adverse events, primarily immune-related but mostly grade ≤3.

The treatment showed promising antitumor activity, with an objective response rate of 30% in one group and a median overall survival of 11.6 months in that group, indicating potential benefits for patients who have not responded to prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of the PD-1 Inhibitor Serplulimab plus the Bevacizumab Biosimilar HLX04 in Patients with Previously Treated Advanced Hepatocellular Carcinoma. Ren, Z., Shao, G., Shen, J., et al.[2023]

In a phase Ib clinical study involving 50 patients with advanced hepatocellular carcinoma (HCC), the combination of sintilimab and IBI305 showed an overall response rate of 34% and a median overall survival of 20.2 months, indicating its efficacy as a treatment.

Biomarker analysis revealed that higher serum levels of CD137 and greater infiltration of M1 macrophages in tumors were associated with better clinical outcomes, suggesting these could be potential predictive biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum Concentration of CD137 and Tumor Infiltration by M1 Macrophages Predict the Response to Sintilimab plus Bevacizumab Biosimilar in Advanced Hepatocellular Carcinoma Patients. Zhang, W., Gong, C., Peng, X., et al.[2023]

The IMbrave150 trial has established the atezolizumab-bevacizumab combination as a superior first-line treatment for advanced hepatocellular carcinoma (HCC) compared to sorafenib, marking a significant shift in treatment protocols after more than a decade.

Other emerging immunotherapy combinations, such as durvalumab-tremelimumab and lenvatinib-pembrolizumab, are also showing promise in phase III studies, indicating a potential for further changes in the standard of care for HCC and highlighting the need for careful selection of first-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Challenges Facing Systemic Therapies of Advanced HCC in the Era of Different First-Line Immunotherapy-Based Combinations. Edeline, J., Meyer, T., Blanc, JF., et al.[2023]

References

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

Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

The effect of anti-CTLA4 treatment on peripheral and intra-tumoral T cells in patients with hepatocellular carcinoma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Phase 2 Study of the PD-1 Inhibitor Serplulimab plus the Bevacizumab Biosimilar HLX04 in Patients with Previously Treated Advanced Hepatocellular Carcinoma. [2023]

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

Serum Concentration of CD137 and Tumor Infiltration by M1 Macrophages Predict the Response to Sintilimab plus Bevacizumab Biosimilar in Advanced Hepatocellular Carcinoma Patients. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

New Challenges Facing Systemic Therapies of Advanced HCC in the Era of Different First-Line Immunotherapy-Based Combinations. [2023]