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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments: Domvanalimab and Zimberelimab, both experimental, to determine their effectiveness in treating liver and bile duct cancers unresponsive to previous treatments. The main goal is to assess whether these drugs can slow or halt cancer growth. Individuals with advanced liver or bile duct cancer, who did not improve with earlier treatments and are not eligible for surgery, may be suitable for this trial. Participants should have measurable disease and must not have had a liver transplant. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to potentially benefit from new therapies.

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.

Is there any evidence suggesting that the combination of Domvanalimab and Zimberelimab is likely to be safe for humans?

Research has shown that the combination of Domvanalimab and Zimberelimab has been tested for safety in other types of cancer. These studies indicate that this combination is generally well-tolerated. Some patients have experienced side effects, but they are usually manageable. Common side effects include fatigue, nausea, or reactions at the injection site. More serious side effects are less common.

Since this trial is in an earlier phase, the treatment has already passed initial safety tests in humans. Researchers remain confident about its safety but continue to learn more about patient tolerance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Domvanalimab and Zimberelimab for liver cancer because they represent a new way to tackle this tough-to-treat condition. Unlike traditional treatments like surgery, chemotherapy, or targeted therapies, these drugs are monoclonal antibodies that work by boosting the body's immune response against cancer cells. Domvanalimab targets the TIGIT pathway, a novel mechanism, while Zimberelimab inhibits PD-1, helping to unleash immune cells to attack the tumor more effectively. This combination has the potential to enhance the immune system's ability to fight liver cancer, offering hope for improved outcomes.

What evidence suggests that the combination of Domvanalimab and Zimberelimab could be effective for advanced liver cancer?

Research has shown that the combination of Domvanalimab and Zimberelimab, which participants in this trial will receive, may help treat certain advanced cancers. In one study with patients who had various advanced cancers, about 17 out of every 100 patients experienced tumor shrinkage or disappearance, known as an objective response rate (ORR) of 17.2%. The study also found that patients lived for about 4.4 months on average without disease progression, referred to as median progression-free survival (PFS). These findings suggest that this drug combination could help manage advanced liver and bile duct cancers after other treatments have failed. ^{1 2 3 5 6}

Who Is on the Research Team?

David Hsieh, MD

Principal Investigator

Assistant Professor

Are You a Good Fit for This Trial?

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 advanced cancer cannot be treated with surgery or localized therapies, or it has worsened after such treatments.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

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clinicaltrials.gov

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NCT05724563 | Domvanalimab and Zimberelimab in ...

If the combination of Domvanalimab and Zimberelimab are effective in treating advanced hepatobiliary cancers that have failed prior treatment. Official Title.

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Study Details | NCT04791839 | Safety and Efficacy of ...

Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small ...

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withpower.com

withpower.com/trial/phase-2-liver-neoplasms-6-2023-4540f

Domvanalimab + Zimberelimab for Liver Cancer

The combination of tremelimumab and durvalumab (T300 + D) showed the highest overall survival rate (18.7 months) and objective response rate (24.0%) among ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12219336/

Dual TIGIT and PD-1 blockade with domvanalimab plus ...

Among the 29 patients enrolled, the confirmed ORR was 17.2% (95% CI 5.8%-35.8%) and the median PFS was 4.4 months (95% CI, 4.1–4.6 months).

5.

clinicaltrials.eu

clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-domvanalimab-and-zimberelimab-for-adults-with-advanced-rare-cancers-resistant-to-standard-treatment/

Study on the Safety and Effectiveness of Domvanalimab ...

This study investigates the safety and effectiveness of Domvanalimab and Zimberelimab for adults with advanced rare cancers, ...

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io.nihr.ac.uk

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Health Technology Briefing April 2025

Domvanalimab with zimberelimab, administered through an injection into a vein, could provide a new treatment for patients with previously.