Atezolizumab in Combination With a Multi-Kinase Inhibitor for the Treatment of Unresectable, Locally Advanced, or Metastatic Liver Cancer

Recruiting now · Phase 2

Conditions studied: 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

In brief

This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib and lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cabozantinib or lenvatinib may kill more tumor cells in patients with liver cancer.

Key facts

Study ID

NCT05168163

Run by

Academic and Community Cancer Research United

People needed

122

Starts

2022-05-27

Expected to finish

2026-12-31

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Provide written informed consent =< 28 days prior to randomization
• 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 and clinical follow-up), participants must be willing to return to the consenting institution for follow-up
• Age >= 18 years
• Hepatocellular carcinoma (HCC) confirmed by histological/cytological diagnosis or clinically per the American Association for the Study of Liver Diseases (AASLD) or WASL 2018 criteria
• Locally advanced, metastatic and/or unresectable disease that is not amendable to curative treatment
• Previously progressed on atezolizumab in combination with bevacizumab as first line systemic therapy for advanced disease
• NOTE: 2nd line patients only
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Child Pugh class A
• Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) serology tests.
• For subjects with active HBV, HBV deoxyribonucleic acid (DNA) < 500 IU/mL obtained ≤ =< 28 days prior to randomization, and anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study
• At least one measurable untreated malignant lesion per RECIST v1.1. Subjects who previously received local therapy (e.g., ablation, percutaneous ethanol injection, trans-arterial embolization/chemo-embolization) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1
• Consent to using archival tumor tissues, if available
• NOTE: Non-availability of tumor tissue does not exclude the subject.
• Willingness to provide mandatory blood specimens for correlative research
• Willingness to provide mandatory tissue specimens for correlative research for the first 10 patients per arm (Mayo Clinic Rochester and Mayo Clinic Arizona ONLY)
• Absolute neutrophil count (ANC) >= 1.5 x 10\^9/L (1500/uL) without granulocyte colony-stimulating factor support (obtained =< 28 days prior to randomization)
• Lymphocyte count >= 0.5 x 10\^9/L (500/uL) (obtained =< 28 days prior to randomization)
• Platelet count >= 75 x 10\^9/L (75,000/uL) (obtained =< 28 days prior to randomization)
• Hemoglobin >= 90 g/L (9 g/dL) (obtained =< 28 days prior to randomization)
• Subjects may be transfused to meet this criterion
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =< 5 x upper limit of normal (ULN) (obtained =< 28 days prior to randomization)
• Total bilirubin =< 3 x ULN (obtained =< 28 days prior to randomization)
• Serum albumin >= 30 g/L (3.0 g/dL) (obtained =< 28 days prior to randomization)

You may not qualify if…

• Known diagnosis of fibrolamellar carcinoma, sarcomatoid carcinoma or mixed hepatocellular cholangiocarcinoma
• Prior multi-kinase inhibitor treatment for advanced disease (e.g., cabozantinib, lenvatinib, sorafenib, regorafenib)
• NOTE: Use of multi-kinase inhibitor(s) for adjuvant or as part of loco-regional therapies is allowed as long as the therapy was completed >= 6 months prior to randomization
• Any of the following prior therapies:
• Major surgery =< 4 weeks prior to randomization; Minor surgery =< 7 days prior to randomization (e.g., simple excision, tooth extraction, insertion of central lines/Mediport). Subjects with clinically relevant complications from prior surgery are not eligible
• Any anti-cancer agent =< 2 weeks prior to randomization
• Radiation therapy =< 4 weeks (1 week for palliative radiation for bone metastases and/or for pain control) or radionuclide treatment (e.g., I-131 or Y-90) =< 6 weeks prior to randomization
• Treatment with investigational therapy =< 28 days prior to randomization
• Known brain or leptomeningeal metastasis
• Known co-infection of HBV and HCV. Subjects with a history of HCV infection but who are negative for HCV ribonucleic acid (RNA) by polymerase chain reaction (PCR) will be considered non-infected with HCV
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
• Subjects with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
• Subjects with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• Subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., subjects with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
• Rash must cover < 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the subject at high risk from treatment complication
• Treatment with a live, attenuated vaccine =< 4 weeks prior to randomization, or anticipation of need for such a vaccine during atezolizumab treatment or =< 5 months after the last dose of atezolizumab
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
• Subjects with untreated or incompletely treated esophageal/gastric varices with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to local institutional standards) without any episodes of recurrent gastrointestinal bleeding requiring transfusion or hospitalization for > 28 days prior to randomization are eligible
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) =< 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to randomization

Where it is running

• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (enrolling)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (enrolling)
• Roswell Park Cancer Institute — Buffalo, New York, United States (enrolling)
• Allegheny General Hospital — Pittsburgh, Pennsylvania, United States (enrolling)
• Rapid City Regional Hospital — Rapid City, South Dakota, United States (enrolling)
• Froedtert and the Medical College of Wisconsin LAPS — Milwaukee, Wisconsin, United States (enrolling)
• Mayo Clinic in Arizona — Scottsdale, Arizona, United States (enrolling)
• Carle Cancer Center NCI Community Oncology Research Program — Urbana, Illinois, United States (enrolling)
• University Medical Center New Orleans — New Orleans, Louisiana, United States (enrolling)
• Michigan Cancer Research Consortium NCORP — Ann Arbor, Michigan, United States (enrolling)
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• Cleveland Clinic Weston Florida — Weston, Florida, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• Duke University Medical Center — Durham, North Carolina, United States
• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States

Full record on ClinicalTrials.gov

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