Domvanalimab and Zimberelimab in Advanced Liver Cancers

NCT05724563 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SCCC-20Y22; STU-2022-1076
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatobiliary Cancer; Liver Cancer; Cholangiocarcinoma; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response rate of combination zimberelimab and domvanalimab.

  To determine the best objective response rate assessed by RECIST guidelines (version 1.1) of combination zimberelimab and domvanalimab in patients with advanced hepatobiliary cancers previously exposed to anti-PD-1/L1 antibody treatments.

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

Secondary Outcomes (5)

• Disease Control Rate of combination zimberelimab and domvanalimab

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

• Overall survival of combination zimberelimab and domvanalimab

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

• 6-month progression-free survival of combination zimberelimab and domvanalimab

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

• Duration of response of combination zimberelimab and domvanalimab

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

• Number of participants with Adverse Events (AEs) (serious / non-serious) as defined by CTCAE v5.0

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

Study Arms (1)

Zimberelimab and Domvanalimab

EXPERIMENTAL

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

Drug: Zimberelimab; Drug: Domvanalimab

Interventions

Zimberelimab DRUG

Zimberelimab 360 mg IV every 3 weeks until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

Also known as: AB122

Zimberelimab and Domvanalimab

Domvanalimab DRUG

Domvanalimab 1200 mg IV every 3 weeks until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

Also known as: AB154

Zimberelimab and Domvanalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have a histologically confirmed diagnosis consistent with HCC or bile duct cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancers); known fibrolamellar HCC, or combined HCC-cholangiocarcinoma will be excluded.
• Locally advanced or metastatic disease
• a. Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
• b. Measurable disease, as defined as lesions that can accurately be measured in at east one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).
• Refractory to or relapsed after prior anti-PD-1/L1 antibody therapy. May have received anti-PD-1/L1 monotherapy or combination therapy as any line of therapy including in the neoadjuvant or adjuvant setting. Patients who discontinued prior immune checkpoint inhibitor treatment due to toxicity are not eligible.
• Availability of recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or slides in which the biopsy or resection was performed within 3 years. Baseline tissue can be obtained after consent but must be prior to initiation of zimberelimab and domvanalimab. It is strongly recommended that tissue is obtained from biopsies confirming progression of disease on prior therapy so that the patient has not received any intervening systemic anti-cancer treatment from the time that the baseline tissue was obtained.
• Prior locoregional is allowed provided the following are met: 1) at least 2 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation; 2) target lesion has increased in size ≥25% or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion and radiotherapy will be completed at least 2 weeks prior to study drug administration.
• Age ≥ 18 years
• Child-Pugh Score A or B7-8 (only for Cohort A)
• ECOG Performance score of 0-1
• Adequate organ and marrow function (without chronic, ongoing growth factor support or transfusion in the last 2 weeks) as defined below:
• a. Platelet count ≥ 50,000/mm\^3
• b. Hgb ≥ 8.5 g/dl
• c. Absolute neutrophil ≥ 1,000 cells/mm\^3
• d. Total bilirubin ≤ 3.0 mg/ml (This will not apply to subjects with Gilbert's syndrome who have persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis, and such patients may be enrolled based in consultation with the principal investigator).

You may not qualify if:

• Prior liver transplant.
• Known human immunodeficiency virus (HIV) positive (testing not required).
• Use of any live vaccines against infectious diseases within 28 days of first dose of study drug administration.
• History of trauma or major surgery within 28 days prior to the first dose of study drug administration. (Tumor biopsy or placement of central venous access catheter (eg, port or similar) is not considered a major surgical procedure).
• Underlying medical conditions that, in the investigator's opinion, will make the administration of study drugs hazardous, including but not limited to:
• a. Interstitial lung disease, including history of interstitial lung disease or non infectious pneumonitis (lymphangitic spread of cancer is not disqualifying),
• b. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of study drugs,
• c. Clinically significant cardiovascular disease,
• d. A condition that may obscure the interpretation of toxicity determination or AEs,
• e. History of prior solid-organ transplantation.
• Hypersensitivity to IV contrast; not suitable for pre-medication.
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
• Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
• a. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• b. Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Arcus Biosciences, Inc.: collaborator
• Cancer Prevention Research Institute of Texas: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Related Publications (1)

• Hsiehchen D, Kainthla R, Kline H, Siglinsky E, Ahn C, Zhu H. Dual TIGIT and PD-1 blockade with domvanalimab plus zimberelimab in hepatocellular carcinoma refractory to anti-PD-1 therapies: the phase 2 LIVERTI trial. Nat Commun. 2025 Jul 1;16(1):5819. doi: 10.1038/s41467-025-60757-7.

  PMID: 40592848 DERIVED

MeSH Terms

Conditions

Liver Neoplasms; Cholangiocarcinoma; Carcinoma, Hepatocellular

Interventions

zimberelimab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• David Hsieh, MD

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Internal Medicine

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 13, 2023
• Study Start: June 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)