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

NCT05199285 | Terminated Phase 2 DMC FDA Drug

• 3 other identifiers: ACCRU-GI-2017NCI-2021-13335P30CA015083
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 5

Brief 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). 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.

Conditions

BCLC Stage B Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma; Locally Advanced Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v8; Stage IIIA Hepatocellular Carcinoma AJCC v8; Stage IIIB Hepatocellular Carcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8; Stage IVA Hepatocellular Carcinoma AJCC v8; Stage IVB Hepatocellular Carcinoma AJCC v8; Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (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.

  Up to 6 months

Secondary Outcomes (4)

• Overall survival (OS)

  Assessed up to 2 years

• Progression-free survival (PFS)

  Assessed up to 2 years

• Disease control

  Up to 2 years

• Incidence of adverse events

  Up to 2 years

Study Arms (1)

Treatment (nivolumab, ipilimumab)

EXPERIMENTAL

Patients 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.

Biological: Ipilimumab; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Treatment (nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (nivolumab, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

University of Alabama- Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

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; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Mehmet Akce

  Academic and Community Cancer Research United

  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: SPONSOR

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: January 20, 2022
• Study Start: January 19, 2023
• Primary Completion: September 4, 2025
• Study Completion: September 4, 2025
• Last Updated: October 3, 2025

Record last verified: 2025-09

Locations

US (5)