Milciclib Phase 2a Trial - Tolerability Update
Released : May 16, 2018
Tiziana Life Sciences plc
("Tiziana" or the "Company")
Tiziana Life Sciences Announces Interim Analysis Data from an Ongoing Phase 2a Trial of Milciclib Safety and Tolerability in Sorafenib-refractory or -intolerable, Unresectable or Metastatic Hepatocellular Carcinoma (HCC) Patients
Treatment with Milciclib (100 mg once daily; 4 day On/3 day Off every four weeks defining each cycle) was well-tolerated for up to 6 cycles in this population of HCC patients
London, 16 May, 2018 - Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology company developing targeted drugs for cancer and inflammatory diseases, today announces that the independent data monitor committee (IDMC) completed a second, interim analysis of tolerability data from the first eleven treated patients and recommended expansion of the initial cohort to continue enrolment of an additional 20 patients to complete the trial.
This phase 2a multi-centre and multi-country clinical trial (CDKO-125A-010) in sorafenib-refractory or -intolerable patients with unresectable or metastatic HCC is being conducted in Greece, Italy and Israel. Since, this was the first trial with milciclib in HCC patients, a second, interim analysis was scheduled following completion of treatment for the first 11 patients before initiating enrolment of the next 20 patients. Thus, demonstration of good tolerability with acceptable incidence of serious adverse events is an important milestone to initiate a phase 2b trial evaluating combination of milciclib with sorafenib (NexavarÒ; Bayer Germany (BAYN.GR)) in HCC patient.
Major findings were as follows:
·Milciclib treatment was well-tolerated with manageable drug-related toxicities. The IDMC concluded that there were no major signals of tolerability concerns and therefore favours proceeding to expand enrolment.
·Four patients have completed the study per protocol (6 cycles of treatment in 6 months). Two of these patients and their care provider opted to continue receiving milciclib at full dose as part of compassionate use. A third patient is awaiting ethical committee (EC) approval.
Gabriele Cerrone, Chairman of Tiziana Life Sciences, commented: "Establishment of tolerability of milciclib as a single agent in HCC patients is a key pre-requisite to initiate the phase 2b trial to evaluate dosing, tolerability and clinical activity of milciclib in combination with sorafenib (NexavarÒ; Bayer Germany) in HCC patients.
Kunwar Shailubhai, CEO & CSO of Tiziana Life Sciences, commented: "we are pleased with the conclusion of IDMC that milciclib treatment showed no major signals of tolerability concerns in sorafenib-refractory or -intolerable HCC patients. These findings are consistent with the findings reported earlier on the long-term tolerability and clinical activity of milciclib in thymic carcinoma, thymoma1 and other solid cancers2. Results from these clinical studies strongly warrant further clinical development of milciclib for treatments of HCC and other cancers".
1. Press Release on announcement of clinical data in thymoma and thymic carcinoma.
2 . Aspeslagh, S., Shailubhai, K., Bahleda, R. et al. (2017). Phase I dose-escalation study of Milciclib in combination with gemcitabine in patients with refractory solid tumors. Cancer Chemother Pharmacol. 79:1257-1265
About Hepatocellular Carcinoma
Hepatocellular cancer is the 5th most common cancer and the 3rd cause of cancer mortality worldwide. In 2007 the approval by the European Medical Agency (EMA) and Food and Drug Administration (FDA) of sorafenib in HCC represented the first systemic therapy for improving outcome in patients unsuitable for loco-regional and surgical therapies and created a new standard of treatment for the disease. However, although significant in respect to placebo, the benefits of sorafenib are modest; the response rate is less than 3%, the improvement in median survival is 2-3 months and the drug-related symptoms are not ordinary. Therefore, more effective systemic therapy is required for both naive patients presenting with unresectable, advanced stage and those who suffer recurrence after curative treatments (resection, ablation and transplantation).
Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases (CDKs) such as CDK1, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signalling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. In a phase I study, oral treatment with Milciclib was found to be well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in thymic carcinoma, pancreatic carcinoma and colon cancer.
Sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar) is a small molecular multi tyrosine kinase inhibitor drug approved for the treatment of primary kidney cancer (advanced renal cell carcinoma), advanced primary liver cancer (HCC), and radioactive iodine resistant advanced thyroid carcinoma. Treatment with sorafenib induces autophagy, which may suppress tumor growth. However, autophagy can also cause drug resistance.
About Tiziana Life Sciences
Tiziana Life Sciences plc is a UK biotechnology company that focuses on the discovery and development of novel molecules that treat human disease in oncology and immunology. The Company is focused on its lead compound Milciclib. The Company is also in clinical development of foralumab. Foralumab is the only fully human engineered anti-CD3 antibody in clinical development. This phase 2 compound has potential application in a wide range of autoimmune and inflammatory diseases, such as non-alcoholic steatohepatitis (NASH), primary biliary cholangitis (PBS), ulcerative colitis, multiple sclerosis, type-1 diabetes (T1D), inflammatory bowel disease (IBD), psoriasis and rheumatoid arthritis, where modulation of a T-cell response is desirable.
For more information go to http://www.tizianalifesciences.com
This announcement contains inside information for the purposes of Article 7 of EU Regulation 596/2014.
The content of this announcement has been reviewed and approved for publication by Dr Kunwar Shailubhai, CEO & CSO of the Company.
Tiziana Life Sciences plc
Gabriele Cerrone, Chairman and founder
+44 (0)20 7493 2853
Cairn Financial Advisers LLP (Nominated adviser)
Liam Murray / Jo Turner
+44 (0)20 7213 0880
This information is provided by RNS