Adaptive Dosing of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma

NCT07689175 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU20261069
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if immunotherapy including nivolumab plus ipilimumab is effective and safe in treating hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• Disease control rate after immunotherapy nivolumab plus ipilimumab

  To determine the proportion of patients with imaging evidence of subsequent disease control (stable disease, partial response, or complete response); Per RECIST v.1.1. among subjects who attained an initial favorable imaging response.

  From time of initial treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

Secondary Outcomes (6)

• Overall response rate of combination nivolumab plus ipilimumab

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

• Favorable response rate combination immunotherapy nivolumab plus ipilimumab

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

• Objective response rate of combination immunotherapy nivolumab plus ipilimumab

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

• Progression-free survival of combination immunotherapy nivolumab plus ipilimumab

  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 to immunotherapy nivolumab plus ipilimumab

  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)

Nivolumab plus ipilimumab

EXPERIMENTAL

Administration: * Route: Intravenous (IV) infusion only. * Schedule and Dose: * Cycles 1-4: Nivolumab 1 mg/kg IV every 3 weeks Ipilimumab 3 mg/kg mg IV every 3 weeks o Subsequent cycles: Nivolumab 480 mg IV every 4 weeks

Drug: Nivolumab; Drug: Ipilimumab (3 mg/kg)

Interventions

Nivolumab DRUG

Nivolumab 1 mg/kg every 3 weeks for a maximum of 4 doses as part of combination therapy; then 240 mg every 2 weeks or 480 mg every 4 weeks as single agent.

Nivolumab plus ipilimumab

Ipilimumab (3 mg/kg) DRUG

ipilimumab 3 mg/kg for a maximum of 4 doses as part of combination therapy, for a maximum of 4 doses.

Nivolumab plus ipilimumab

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 diagnosis confirmed by histology or clinically by the American Association for the Study of Liver Diseases (AASLD) criteria in patients with cirrhosis. Known fibrolamellar HCC or combined HCC-cholangiocarcinoma will be excluded.
• Patients may not have received any prior anti-PD-1/L1 or anti-CTLA-4 therapies for the treatment of advanced HCC.
• 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.
• Child-Pugh Score B7-8
• Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST v.1.1.
• Prior locoregional therapy is allowed provided the target lesion has increased in size ≥25% since the cessation of locoregional therapy 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.
• Age ≥ 18 years.
• ECOG performance score 0-2
• Adequate organ and marrow function as defined below:
• Platelet count ≥ 40,000/mm3
• Hgb ≥ 8 g/dl
• INR ≤ 2
• AST, ALT ≤ 5 times ULN
• Calculated creatinine clearance (CrCl) ≥ 35 mL/min. CrCl can be calculated using the Cockcroft-Gault method.
• Albumin ≥ 2.0 g/dl

You may not qualify if:

• Prior solid organ transplant.
• Hypersensitivity to IV contrast; not suitable for pre-medication.
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Active autoimmune disease that requires current systemic treatment (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for conditions that, in the investigator's opinion, do not have a substantial hazardous risk such as asthma, and cutaneous and musculoskeletal rheumatologic conditions.
• Known human immunodeficiency virus infection (testing not required) in a patient not on antiretroviral therapy and detectable viral load.
• Prior malignancy that required systemic treatment within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer. Preneoplastic or malignant diagnoses that are indolent in nature and do not require active systemic treatment are not excluded.
• If a participant has symptomatic or clinically active brain metastases including leptomeningeal disease, they must be excluded if:
• Has evidence of progression by neurologic symptoms
• Has metastatic brain lesions that require immediate intervention.
• Has carcinomatous meningitis, regardless of clinical stability
• Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Prisoners or subjects who are involuntarily incarcerated.
• Has significant dementia or other mental condition that precludes the participant's ability to consent to the study.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Hsieh, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carrie Manwaring, BS

CONTACT

214-648-7097; carrie.manwaring@utsouthwestern.edu

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: Associate Professor, Internal Medicine

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 8, 2026
• Study Start (Estimated): October 31, 2026
• Primary Completion (Estimated): October 31, 2031
• Study Completion (Estimated): October 31, 2032
• Last Updated: July 8, 2026

Record last verified: 2026-06

Locations

US (1)