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IngenOx Therapeutics –26th February 2025, the Oxford-based biopharmaceutical company, announced today positive interim results from its Phase 2 clinical trial investigating zabadinostat in combination with a PD-1 inhibitor for advanced hepatocellular carcinoma (HCC). The findings were presented at The Lancet Summit 2025 in Shanghai, China.
Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced HCC. While some patients experience lasting responses, resistance to therapy is a common challenge. Collaborative preclinical research has shown that IngenOx’s zabadinostat reversed resistance to immune checkpoint inhibition in a clinically relevant orthotopic mouse HCC model (Tu et al., 2024). This study provided a strong scientific rationale for the clinical development of zabadinostat in combination with an ICI as a treatment for HCC patients who have become resistant to checkpoint blockade.
IngenOx is supporting a randomised Phase 2 clinical trial conducted by the Chinese University of Hong Kong (CUHK) to evaluate the safety and efficacy of zabadinostat combined with geptanolimab in ICI-resistant HCC patients (Experimental Arm), compared with a tyrosine kinase inhibitor such as lenvatinib or sorafenib (Control Arm). Geptanolimab is an ICI that targets the programmed cell death-1 (PD-1) receptor.
Interim results were presented by investigators at The Lancet Summit on Cancer Control in China, recently held in Shanghai (https://thelancetsummit.com/cancer-control-china/index.html). The results showed that the experimental combination with zabadinostat was associated with a higher disease stabilisation rate (61.5%; 95% CI 35–88%; n = 13) compared to the control group (46.2%; 95% CI 19–73%; n = 13). No difference in progression-free survival was observed between the groups. Median overall survival was 13.9 months (95% CI 8–14) in the Experimental Arm, compared to 9.3 months (95% CI 2–NR) in the Control Arm (HR 0.16, 95% CI 0.08–1.36, p = 0.12). These preliminary findings indicate that the combination therapy is well tolerated, associated with a higher disease control rate, and suggests a trend towards improved outcomes. The positive clinical results support the continued development of zabadinostat combinations for advanced cancer treatment.
David Kerr, CMO of IngenOx and Professor of Cancer Medicine at the University of Oxford commented:
“These promising clinical trial findings give us great confidence that we can recapitulate in patients the extraordinary results seen in mice models and deliver a telling blow to this awful disease. Our sophisticated trial design gives us the necessary clinical data to continue recruitment and stays true to our commitment to precision medicine as we interrogate the serial biopsies from our patients to discover potentially predictive biomarkers to further improve clinical outcomes.”
Nick La Thangue, CEO of IngenOx and Professor of Cancer Biology at the University of Oxford commented:
“These encouraging early results continue to endorse zabadinostat as a potentially significant drug in resistant liver cancer. We are pleased to support this trial and look forward to continuing our important collaboration with colleagues in Hong Kong.”
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About IngenOx Therapeutics
IngenOx Therapeutics is a biopharmaceutical company focused on delivering new precision medicine drugs and vaccines to treat the most difficult cancers, often referred to as cold tumours. It is a spinout from the University of Oxford and is located in the Oxford Science Park, UK. Its pipeline comprises early to late-stage products that work in different ways to activate the immune response against cold tumours, which are generally poorly recognised by the immune system. An exciting proprietary platform technology focuses on precision cancer vaccines that act by targeting the immune response to a novel source of cancer antigens.
The company has secured multiple rounds of investment and has numerous license and partnership agreements in place.
For more information see www.ingenox.com
About the Chinese University of Hong Kong
Founded in 1963, The Chinese University of Hong Kong (CUHK) is a forward-looking comprehensive research university with a global vision and a mission to combine tradition with modernity, and to bring together China and the West. CUHK teachers and students hail from all around the world. CUHK graduates are connected worldwide through an extensive alumni network.
For more information see www.cuhk.edu.hk
About The Lancet
The Lancet began as an independent, international weekly general medical journal founded in 1823 by Thomas Wakley. Since its first issue (Oct 5, 1823), the journal has strived to make science widely available so that medicine can serve and transform society as well as positively impact the lives of people.
For more than two centuries, The Lancet has sought to address urgent topics in our society, initiate debate, put science into context, and influence decision makers around the world. The Lancet Group has evolved as a family of journals but retains at its core the belief that medicine must serve society, knowledge must transform society, and the best science must lead to better lives.
For more information see www.thelancet.com
References
Tu, Y., Wu, H., Zhong, C., Liu, Y., Xiong, Z., Chen, S., Wang, J., Wong, P. P., Yang, W., Liang, Z., Lu, J., Chen, S., Zhang, L., Feng, Y., Si-Tou, W. W., Yin, B., Lin, Y., Liang, J., Liang, L., Vong, J. S. L., … Cheng, A. S. (2024). Pharmacological activation of STAT1-GSDME pyroptotic circuitry reinforces epigenetic immunotherapy for hepatocellular carcinoma. Gut, gutjnl-2024-332281. Advance online publication. https://doi.org/10.1136/gutjnl-2024-332281