Top line data from this trial, being conducted in Italy, Israel, Greece and Turkey, is expected in Q4 2018. The primary objective of this multi-centre, multi-country and dose-ranging phase IIa clinical study is to evaluate the safety of milciclib in HCC patients who fail to respond to or are intolerant to the existing standard of care treatment.
Subsequently, a phase IIb is planned with the combination of milciclib with the standard of care treatment sorafenib in HCC patients.
Milciclib is an inhibitor of several cyclin-dependent kinases (CDKs), which are commonly overexpressed in tumours resistant to chemotherapy. Accordingly, the investigational therapy will be tested in patients who have failed to respond to the standard of care treatment, sorafenib (NexavarÒ).
Preclinical studies conducted strongly suggest that milciclib acts primarily through downregulation of microRNA (miR) 221 and 222, which are known to be associated with hepatocarcinogenesis and overexpression of these miRs is also believed to be associated with development of resistance to sorafenib in HCC patients.
In previous phase I clinical studies, oral treatment with milciclib was found to be safe and well-tolerated in patients with advanced solid tumours such as thymoma and thymic carcinoma, pancreatic carcinoma and colon cancer.1 The combination of milciclib with gemcitabine, a well-known nucleoside analogue, in a phase I dose-escalation study showed favourable clinical responses in approximately 36% of patients with advanced/metastatic tumours, including patients previously considered to be resistant to gemcitabine.
Gabriele Cerrone, Chairman of Tiziana Life Sciences, commented: "HCC is a real unmet medical need due to its growing incidence and lack of effective therapy. It is the fifth most common cancer worldwide and the second most common cause of death from cancer worldwide."
Kunwar Shailubhai, CEO & CSO of Tiziana Life Sciences, commented: "Oral treatment with milciclib has been well-tolerated in previous studies with cancer patients. We strongly believe, based on its unique mechanism of action, that the drug may have potential to be developed either as a monotherapy or combo-therapy with sorafenib for treatment of HCC."
Dr. Ilan Yaron, Director of the Department of Medicine at Hebrew University Hadassah Medical Center, Israel and Chief Medical Officer of Tiziana Life Sciences, added: "The prognosis for liver cancer is very poor due to lack of effective therapy. We believe that milciclib holds promise as an effective anti-cancer treatment with a high safety profile."