Hepatocellular carcinoma (HCC)
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and typically arises in the setting of chronic liver disease, including hepatitis B or C infection, alcohol-related liver disease, or nonalcoholic steatohepatitis (NASH). HCC is often diagnosed at an advanced stage and develops within an immunologically tolerant organ, making it particularly challenging to treat. In recent years, immune checkpoint inhibitors—especially anti-PD-L1–based combinations such as PD-L1 plus anti-VEGF therapy—have become standards of care for advanced HCC. However, despite these advances, objective response rates generally remain in the range of ~20–30%, and the majority of patients experience disease progression within the first year of treatment.
Globally, HCC represents a major and growing health burden. It is the sixth most commonly diagnosed cancer worldwide and the third leading cause of cancer-related death. Each year, there are approximately 850,000–900,000 new cases of liver cancer, with hepatocellular carcinoma accounting for the vast majority. Annual deaths from HCC exceed 700,000 worldwide, driven by late diagnosis, limited durable treatment responses, and the complexity of treating cancer in patients with underlying liver dysfunction. These sobering statistics underscore the urgent need for therapies that can meaningfully improve the effectiveness and durability of existing treatments.
Overview of the Adze1.C drug
ADZE1.C is a next-generation oncolytic adenovirus designed to address a fundamental limitation of immunotherapy in HCC: inadequate immune activation within the liver tumor microenvironment. The virus selectively infects and lyses tumor cells, releasing tumor antigens directly in the liver while simultaneously expressing CD40 ligand (CD40L) locally. CD40L activates antigen-presenting cells such as dendritic cells, overcoming immune tolerance in the liver and initiating a stronger anti-tumor immune response. This localized immune activation is designed to increase inflammatory signaling within tumors, including upregulation of PD-L1 expression, a key determinant of responsiveness to checkpoint inhibitors.
By increasing PD-L1 expression and enhancing antigen presentation, ADZE1.C is designed to sensitize hepatocellular carcinoma tumors to existing anti-PD-L1 therapies, improving response rates and potentially extending the durability of benefit. Rather than replacing current standards of care, ADZE1.C is intended to function as an immune-priming partner—strengthening the effectiveness of checkpoint blockade while minimizing the risk of added systemic toxicity. This combination-driven approach offers a promising strategy to improve outcomes for patients with HCC who currently face limited long-term treatment success.
Adze Biotechnology has partnered with Mayo Clinic researchers to advance a Phase 1 clinical trial of ADZE1.C in patients with hepatocellular carcinoma (HCC). This collaboration builds on strong preclinical data demonstrating that ADZE1.C, an oncolytic adenovirus expressing CD40 ligand (CD40L), can significantly enhance anti-tumor immune responses when combined with anti–PD-L1 checkpoint therapy. Mayo Clinic’s leadership in liver cancer research and clinical care provides an ideal setting to translate these findings into the clinic, with the Phase 1 study designed to evaluate the safety, tolerability, and biological activity of ADZE1.C in combination with anti–PD-L1 therapy in patients with advanced HCC.
Based on the robustness of the preclinical combination data, the Mayo Clinic trial will evaluate ADZE1.C administered initially via intratumoral injection, allowing direct immune activation within liver tumors, followed by evaluation of an intravenous route of administration to assess broader applicability and systemic delivery potential. This stepwise clinical approach is intended to characterize immune activation, checkpoint sensitization, and safety across routes of administration while maintaining careful oversight in a patient population with underlying liver disease. Through this partnership, Adze Biotechnology and Mayo Clinic aim to establish a strong clinical foundation for ADZE1.C as an immune-priming partner to anti–PD-L1 therapies, with the goal of improving response rates and durability for patients with hepatocellular carcinoma.
Adze1.C therapy is available in a Phase 1 clinical study in metastatic melanoma in Australia through the Tasman Health Clinic, a specialist centre experienced in advanced and investigational cancer immunotherapies. The clinic focuses on providing personalised care for patients with complex or advanced cancers, including metastatic melanoma, and works within Australian medical and ethical standards.
Patients can access the Tasman Health Clinic by referral or direct enquiry. The clinical team can provide detailed information about eligibility, assessment requirements, and next steps. For Australian melanoma patients exploring additional therapy options, the clinic offers a supportive environment where treatment decisions are made collaboratively and transparently.
For more information, please visit tasmanhealthcare.com.au
For more information on our study, please also see clinicaltrials.gov