Domvanalimab + Zimberelimab for Liver Cancer

Recruiting in Palo Alto (17 mi)

Overseen by David Hsieh, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Texas Southwestern Medical Center Dallas, TX

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center Lead Sponsor

Cancer Prevention Research Institute of Texas Collaborator

Arcus Biosciences, Inc. Industry Sponsor

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] This phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a single, priming dose of tremelimumab (ClinicalTrials.gov identifier: NCT02519348).

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] Checkpoint inhibitors have recently been approved for the treatment of patients with hepatocellular carcinoma (HCC). However, biomarkers, which will help identify patients responding to therapy, are missing. We recently tested the combination of anti-CTLA4 treatment (tremelimumab) with loco-regional therapy in patients with HCC and reported a partial response rate of 26%.

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] Current treatments for patients with previously treated advanced hepatocellular carcinoma (HCC) provide modest survival benefits. We evaluated the safety and antitumor activity of serplulimab, an anti-PD-1 antibody, plus the bevacizumab biosimilar HLX04 in this patient population.

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] This study aimed to investigate the biomarkers of sintilimab (anti-PD-1) plus IBI305 (a bevacizumab biosimilar) in advanced hepatocellular carcinoma (HCC), as well as their safety and efficacy.

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] The standard of care of first-line systemic therapy for advanced hepatocellular carcinoma (HCC) is currently changing with the results of the IMbrave150 trial which are demonstrating superiority of the atezolizumab-bevacizumab combination over sorafenib, modifying this line of treatment for the first time in over 10 years. Recently, other immunotherapy-based combinations (durvalumab-tremelimumab, lenvatinib-pembrolizumab, cabozantinib-atezolizumab, and camrelizumab-rivoceranib) reported results in phase III studies, and might challenge this new standard of care. This revolution will lead to a considerable change in practice, and highlight challenges for future drug development. In this review, we will, firstly, describe results of the different combinations, and discuss the difficulties in selecting the first-line treatment. We will then present the different recommendations about second-line treatment following the first-line immunotherapy-based combination, discussing the rationale for the differences in existing recommendations. We will finally discuss the challenges for future drug development in advanced HCC.