A promising avenue of clinical research in liver cancer is the use of immune checkpoint inhibitors. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses. Several checkpoint inhibitors, targeting multiple different checkpoints, are currently in development. These trials may not be available for patients who have past or present hepatitis due to viral infection. This is because activation of the immune system in the presence of viral hepatitis may cause damage to normal liver cells.
- A phase III trial testing nivolumuab (Opdivo®) versus sorafenib (Nexavar®) as a first-line treatment for patients with advanced liver cancer (NCT02576509).
- A phase I/II study testing nivolumab (Opdivo®) and/or ipilimumab (Yervoy®) in advanced liver cancer with or without chronic hepatitis (NCT01658878).
- A phase I/II trial of nivolumab (Opdivo®) and galunisertib, a TGF-beta receptor 1 kinase inhibitor, in patients with advanced cancers, including liver cancer (NCT02423343).
- Tremelimumab, an antibody targeting the CTLA-4 molecule, is being tested along with chemoembolization or ablation in a phase I clinical trial for patients with liver cancer (NCT01853618).
- MEDI4736, a PD-L1-targeting antibody, and/or tremelimumab are being tested in a phase I/II trial for patients with unresectable liver cancers (NCT02519348).
- A phase I trial of BMS-986016 (an anti-LAG-3 antibody) with or without nivolumab (Opdivo®) for patients with solid tumors, including liver cancer (NCT01968109).
Monoclonal antibodies (mAbs) are molecules, generated in the lab, that target specific antigens on tumors. Many antibodies are currently used in cancer treatment, and some appear to generate an immune response. Several antibodies are currently being tested in clinical trials:
- A phase III trial testing ramucirumab (Cyramza®), an antibody targeting epidermal growth factor receptor (EGFR), a molecule that often appears in high amounts on the surface of cancer cells and helps them grow, in patients with liver cancer following first-line therapy with sorafenib (Nexavar®) (NCT02435433).
- A phase I/II trial testing IMMU-132, an antibody-drug conjugate targeting Τrop-2, in patients with liver and other cancers, and without hepatitis B or C (NCT01631552).
- A phase I/II trial of TRC105, a monoclonal antibody to CD105/endoglin, which is essential for angiogenesis, in patients with liver cancer (NCT01306058, NCT02560779).
Another major avenue of immunotherapy for liver cancer is adoptive T cell transfer. In this approach, T cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response.
- A phase II trial taking enriched tumor-infiltrating immune cells and re-infusing them in patients with metastatic digestive tract cancers, including liver cancer without hepatitis B or C (NCT01174121).
Oncolytic virus therapy uses a modified virus that can cause tumor cells to self-destruct and generate a greater immune response against the cancer.
- A phase III trial of pexastimogene devacirepvec (Pexa-Vec), a vaccina virus-based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells, followed by sorafenib (Nexavar®) in patients with advanced liver cancer who have not received prior systemic therapy (NCT02562755).
Go to our Clinical Trial Finder to find clinical trials of immunotherapies for liver cancer that are currently enrolling patients.