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BCLC Stage B Hepatocellular CarcinomaPhase 2NCT05199285

A Phase II Study of Nivolumab + Ipilimumab in Advanced HCC Patients Who Have Progressed on First Line Atezolizumab + Bevacizumab

A Phase 2 study testing Ipilimumab and Nivolumab in people with BCLC Stage B Hepatocellular Carcinoma and BCLC Stage C Hepatocellular Carcinoma, run by Academic and Community Cancer Research United at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial tests whether nivolumab and ipilimumab works to shrink tumors in patients with liver cancer that has spread to nearby tissue or lymph nodes (locally advanced), has spread to other places in the body (metastatic), or cannot be removed by surgery (unresectable). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ipilimumab and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
5 sitesUnited States
Study dates
19 Jan 2023to 1 Feb 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >= 18 years.
  • HCC diagnosis confirmed by histology/cytology or clinically by American Association for Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
  • Locally advanced, metastatic, or unresectable disease.
  • Child Pugh class A.
  • Barcelona clinic liver cancer (BCLC) stage B (not amenable to liver directed therapy) or stage C.
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  • Prior treatment with atezolizumab and bevacizumab combination with radiographic progression that necessitates change in treatment per treating physician. Patients with rapid progression on atezolizumab and bevacizumab (defined as patients who progressed radiographically in the first restaging scan that necessitates change in treatment) are excluded.
  • Washout period >= 4 weeks prior to registration is required since last atezolizumab and bevacizumab dose.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. (Form is available on the Academic and Community Cancer Research United [ACCRU] website).
  • Absolute neutrophil count (ANC) >= 1000/mm ^ 3 (obtained =< 28 days prior to registration).
  • Platelet count >= 60,000/mm^3 (obtained =< 28 days prior to registration).
  • Hemoglobin >= 8.5 g/dL (obtained =< 28 days prior to registration).
  • Total bilirubin =< 3 x upper limit of normal (ULN) (obtained =< 28 days prior to registration).
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 5 x ULN (obtained =< 28 days prior to registration).
  • International normalized ratio (INR) =< 2.3 or Prothrombin time (PT) =< 6 seconds above control OR if patient is receiving anticoagulant therapy and INR is within target range of therapy creatinine =< 1.5x ULN (obtained =< 28 days prior to registration).
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only.
  • Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Provide informed written consent =< 28 days prior to registration.
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study).
  • Note: During the active monitoring phase of a study (i.e., active treatment), participants must be willing to return to the consenting institution for follow-up.
  • Willing to provide mandatory tissue specimens and blood specimens for correlative research purposes.

Who cannot join

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception.
  • Major surgery =< 4 weeks prior to registration.
  • Liver directed therapy (transarterial chemoembolization [TACE], Y-90, liver directed radiation) =< 28 days prior to registration. Prior liver directed therapy > 28 days prior to registration is allowed as long as patient has at least one measurable untreated lesion by RECIST v1.1.
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  • Patients with rapid progression on atezolizumab and bevacizumab (who progressed radiographically in the first restaging scan that necessitates change in treatment) are excluded.
  • Prior treatment =< 4 weeks prior to registration with anti-CTLA-4 antibody for HCC.
  • Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy.
  • Note: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
  • Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection excluding hepatitis C virus (HCV)
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Unstable cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients with chronic HBV infection as evidenced by detectable HBV surface antigen or HBV deoxyribonucleic acid (DNA) are eligible if on antiviral therapy and have HBV DNA < 100 IU/mL. Patients with active or resolved hepatitis C (HCV) infection as evidenced by detectable HCV ribonucleic acid (RNA) or antibody are eligible.
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 4 weeks prior to registration.
  • Other active malignancy =< 2 years prior to registration. Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
  • History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
  • History of allogenic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • History of leptomeningeal carcinomatosis.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Current or prior use of immunosuppressive medication =< 14 days prior to registration. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication).
  • Receipt of live attenuated vaccine =< 30 days prior to registration; Note: Patients, if enrolled, should not receive live vaccine whilst on study treatment and up to 30 days after the last dose of study treatment.
  • Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
  • History of grade 3 or 4 immunotherapy related toxicity NCI CTCAE v5.0 due to prior regimen attributed to atezolizumab.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Alabama- Birmingham

    Birmingham, Alabama, 35233

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

This phase II trial tests whether nivolumab and ipilimumab works to shrink tumors in patients with liver cancer that has spread to nearby tissue or lymph nodes (locally advanced), has spread to other places in the body (metastatic), or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab and ipilimumab may be effective in killing tumor cells in patients with liver cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To investigate the confirmed objective response rate (ORR) of nivolumab and ipilimumab in patients with hepatocellular carcinoma (HCC) who have progressed radiographically on atezolizumab/bevacizumab that necessitates change in treatment.

SECONDARY OBJECTIVES:

  1. To determine the overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with nivolumab and ipilimumab who have progressed radiographically on atezolizumab / bevacizumab that necessitates change in treatment.

II. To determine the progression free survival (PFS) in hepatocellular carcinoma (HCC) patients treated with nivolumab and ipilimumab who have progressed radiographically on atezolizumab/bevacizumab that necessitates change in treatment.

III. To determine the disease control rate in hepatocellular carcinoma (HCC) patients treated with nivolumab and ipilimumab who have progressed radiographically on atezolizumab/bevacizumab that necessitates change in treatment.

IV. To assess the frequency and severity of adverse events in hepatocellular carcinoma (HCC) patients treated with nivolumab and ipilimumab who have progressed radiographically on atezolizumab/bevacizumab that necessitates change in treatment.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 2 years from registration.

Being tested
Ipilimumab, Nivolumab
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010

    Given IV

  • NivolumabBiological

    Also called BMS-936558, CMAB819, MDX-1106, NIVO

    Given IV

Study groups in NCT05199285
Study groupRoleWhat they receive
Treatment (nivolumab, ipilimumab)ExperimentalPatients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Ipilimumab; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Confirmed objective response rate (ORR)

    A confirmed response is defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Disease status will be assessed using response evaluation criteria in solid tumors (RECIST) version (v.) 1.1 criteria. Overall Response Rate (ORR) is defined as the proportion of evaluable patients who achieve confirmed response (CR or PR) while on treatment. The final ORR point estimate and corresponding 95% confidence interval will be reported according to the method of Clopper-Pearson.

    Measured: Up to 6 months

Secondary outcomes (4)

  1. Overall survival (OS)

    Overall survival (OS) is defined as the time from registration to death from any cause. OS will be estimated using the Kaplan-Meier method. Patients who are alive will be censored at the last follow-up date. The median OS and corresponding 95% confidence interval will be reported.

    Measured: Assessed up to 2 years

  2. Progression-free survival (PFS)

    Progression-free survival (PFS) is defined as the time from registration to the first disease progression or death from any cause, where disease progression is determined based on RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. Patients who do not experience disease progression or death while on protocol will be censored at the last disease assessment date. The median PFS and corresponding 95% confidence interval will be reported.

    Measured: Assessed up to 2 years

  3. Disease control

    Disease control is defined as achieving CR, PR, or maintaining SD for at least 6 months while on treatment. Objective status will be assessed using RECIST v. 1.1 criteria. Disease control rate will be calculated as the proportion of evaluable patients who achieve disease control. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper Pearson.

    Measured: Up to 2 years

  4. Incidence of adverse events

    All patients who have initiated treatment will be considered evaluable for adverse event analyses. The rate of patients experiencing a grade 3+ adverse event will be reported using Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2022
  2. Study start19 Jan 2023
  3. Primary completion1 Feb 2026
  4. Study completion1 Feb 2026

Why it stopped: Sponsor has withdrawn support for the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05199285
Sponsor's protocol ID
ACCRU-GI-2017
Other IDs
NCI-2021-13335, ACCRU-GI-2017, P30CA015083
Status last verified
Aug 2026
First submitted
6 Jan 2022
Last updated
4 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab and Nivolumab in people with BCLC Stage B Hepatocellular Carcinoma and BCLC Stage C Hepatocellular Carcinoma, run by Academic and Community Cancer Research United at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor has withdrawn support for the study.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed objective response rate (ORR) (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05199285.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2026.

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