Teclison Announces Publication of Phase 1 Data Demonstrating the Safety and Therapeutic Potential of Tirapazamine Chemoembolization for Patients with Unresectable Liver Cancer
— Tirapazamine (TPZ) with conventional trans-arterial chemoembolization had a good safety profile and promising efficacy signals in early- and intermediate-stage liver cancer, including in patients who had progression or recurrence after standard therapy —
— Of the 17 evaluable patients, including 10 who progressed despite prior therapy, 47% achieved complete response, with a median time to progression of 12.6 months and a median overall survival of 29.3 months —
— Results are consistent with the response rates seen in previous treatment-nai¨ve patient cohort, and support the theory that TPZ chemoembolization could induce complete tumor necrosis —
— The dose was selected for a randomized Phase 2 study to compare TPZ with doxorubicin, a current therapy, using the same embolization protocol —
PRINCETON, N.J., and TAIPEI, Taiwan, June 21, 2022 (GLOBE NEWSWIRE) -- Teclison, a clinical-stage biotechnology company developing innovative cancer therapeutics to induce tumor necrosis and enhance anti-tumor immunity, today announced the peer-reviewed publication of a study demonstrating the safety, tolerability and preliminary efficacy of its trans-arterial tirapazamine chemoembolization (TATE) therapy in patients with unresectable early- and intermediate-stage hepatocellular carcinoma (HCC), also known as liver cancer. The clinical data, published in The Journal of Vascular and Interventional Radiology titled “Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma,” establishes tirapazamine, a hypoxia-activated anti-cancer drug, as safe when administered in conjunction with trans-arterial embolization with promising efficacy in patients with liver cancer, including those with progression or recurrence after treatment with conventional trans-arterial chemoembolization (TACE).
“The current standard of care for unresectable liver cancer is conventional trans-arterial chemoembolization with the chemotherapeutic agent doxorubicin. Though well established, TACE with doxorubicin has limited efficacy because chemotherapy does not effectively kill cancer stem cells, a root cause for tumor recurrence after TACE. Additioally, embolization-induced tumor hypoxia is thought to dampen the cytotoxic effects of doxorubicin,” said Chang-Hsien Liu, MD, principal investigator of the study. “The results of this study support tirapazamine as an alternative to doxorubicin in trans-arterial chemoembolization. A future randomized study is warranted to compare tirapazamine and doxorubicin under embolization.”
Ray Lee, MD, PhD, Founder and CEO of Teclison, added, “We are encouraged by the potential of trans-arterial tirapazamine chemoembolization to improve the clinical response and extend overall survival when administered to patients with liver cancer. This data reinforces findings from our previous first-in-human study published in the Journal of Hepatocellular Carcinoma and establishes the tirapazamine dose for subsequent Phase 2 clinical trials.”
Seventeen patients with unresectable early-stage HCC or unresectable intermediate-stage HCC were enrolled in this non-randomized, open-label Phase 1 study. Prior treatment such as surgery, radiofrequency ablation, and TACE, was permitted. Following a 3 + 3 dose escalation design, patients were assigned to three cohorts with a tirapazamine dose of 5mg/m2, 10mg/mg2 and 20mg/m2, respectively. As no dose-limiting toxicity was observed, the 20mg/m2 dose was converted to a fixed 35mg dose in the expansion cohort. The primary outcomes of the study were safety and tolerability. No serious adverse side effect was reported during the study. Most common adverse effects included transiently elevated liver enzymes, abdominal pain, fever, elevated bilirubin level, and transient ECG abnormality. The secondary endpoint was efficacy of TATE therapy. Of the 17 enrolled patients, 8 achieved complete response (CR 47.1%) as measured radiographically. Three patients achieved a partial response (PR 17.6%) for an overall response rate of 65%. CR rates were comparable between subgroups with and without prior TACE. The six-month progression-free survival rate was 72.6% and the median overall survival (OS) was 29.3 months.
Trans arterial chemoembolization (TACE) is the common therapeutic modality recommended by the Barcelona Clinic Liver Cancer (BCLC) staging system for patients with intermediate or advanced HCC. The overall response rate of TACE is 52% and median OS of about 20 months in a recent systemic review of 10,000 patients. A Phase 2 randomized study comparing efficacy of TATE vs TACE in patients with intermediate liver cancer is underway.