On February 26, 2025 IngenOx Therapeutics the Oxford-based biopharmaceutical company, reported positive interim results from its Phase 2 clinical trial investigating zabadinostat in combination with a PD-1 inhibitor for advanced hepatocellular carcinoma (HCC) (Press release, IngenOx Therapeutics, FEB 26, 2025, https://ingenox.com/interim-phase-2-results-suggest-zabadinostat-combination-improves-overall-survival-in-advanced-liver-cancer [SID1234650630]). The findings were presented at The Lancet Summit 2025 in Shanghai, China.
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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."