Hepatocellular carcinoma: an update on investigational drugs in phase I and II clinical trials

ABSTRACT

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the burden of disease is increasing globally. Until recently, systemic therapies for HCC were limited and prognosis for advanced disease generally poor.

Area covered: This article describes some recent phase I and II clinical trials for the treatment of HCC. We performed a search on Pubmed with keywords hepatocellular carcinoma, phase I clinical trial, phase II clinical trial, and immunotherapy. We also searched https://clinicaltrials.gov and identified relevant trials listed as active. Studies in progress or recently reported were conducted using novel therapies based on targets identified through molecular profiling of tumors or based on insights into immune system dysregulation in HCC. We also identified studies using drugs targeting recently discovered biomarkers such as endoglin or aldo-keto reductase 1c3. The major outcomes were safety and efficacy as measured by response rate, progression-free survival or overall survival.

Expert opinion: HCC is a heterogeneous disease resulting from aberrations in intracellular signaling and immune system dysregulation. Thus, a multisystem approach will be required to deliver personalized therapy. Combination therapies are likely to be future options; it is also possible that modulation of the microbiome might form part of future treatment paradigms.

KEYWORDS:

• Hepatocellular carcinoma
• phase I clinical trial
• phase II clinical trial
• immunotherapy

Article Highlights

• Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the burden of disease is increasing globally.

• Sorafenib was the only approved therapy from 2007 to 2017.

• Regorafenib was the first new FDA approved agent for the treatment of HCC in the second line setting.

• Since 2017, two tyrosine kinase inhibitors – lenvatinib, and cabozantanib, two PD-1 inhibitors – nivolumab and pembrolizumab, as well as a monoclonal antibody ramucirumab, have all received FDA approval.

• Multiple recent phase I and II clinical trials of investigational drugs for the treatment of HCC are ongoing.

• A multisystem approach will be required to deliver personalized therapy.

• Combination therapies are likely to become future options for patients and it is possible that modulation of the microbiome might form part of future treatment paradigms.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.