VSC), a drug discovery and development company focused on autoimmune and cancer indications, will today present initial clinical data for resminostat (4SC-201), a pan-histone deacetylase (HDAC) inhibitor, from the ongoing, two-arm, Phase II SHELTER study in hepatocellular carcinoma (HCC). The data will be presented by the lead investigator, Prof. Dr.
Michael Bitzer, at the "Viszeralmedizin 2010" Symposium, organized by the German Gastroenterology (DGVS) and Visceral Surgery Associations (DGAV) in Stuttgart, Germany. The SHELTER trial is evaluating the efficacy, safety and tolerability of resminostat as a monotherapy or in combination with the current first line therapy standard, sorafenib, in sorafenib-refractory HCC patients.
The poster presentation highlights safety and tolerability data from the first nine patients from this clinical study, which aims to recruit about 60 HCC patients including the dose escalation of the combination of resminostat and sorafenib. Resminostat was safe and well tolerated in the combination arm of the study with doses of up to 400 mg of sorafenib applied continuously every day and 400 mg of resminostat using its Phase I tested "5 + 9" dosing schedule, resulting in 14 day treatment cycles, as well as in the second study arm in which resminostat is applied as monotherapy at a daily dose of 600 mg using again the "5 + 9" dosing schedule.
Furthermore, no pharmacokinetic interactions were observed between resminostat and sorafenib.
At the time of study entry, patients had documented progressive disease under sorafenib therapy.
Following initiation of the trial therapy, a considerable portion of patients showed stabilisation of their disease (Stable Disease according to RECIST criteria) after 6 or 12 weeks of study treatment. Six out of nine patients examined for their tumour disease status after 6 weeks showed Stable Disease, and three out of four patients examined after 12 weeks of therapy displayed continued disease stabilisation. Patients may remain on therapy as long as a clinical benefit is recorded. In certain cases, patients remained stable for more than 12 weeks of study treatment. One patient in the combination arm, receiving 400 mg of resminostat and 400 mg of sorafenib has been treated for 36 weeks with documented Stable Disease.
Prof. Dr. Michael Bitzer, the lead investigator from the University Hospital Tübingen, Germany, commented: "Advanced HCC is an aggressive form of cancer for which there is an especially high medical need for new treatments as there are currently no approved second line therapies for HCC patients. The SHELTER trial provides the evaluation for a new mechanism of action in this indication, which may hold promise for these patients who have no treatment options left."
Dr. Bernd Hentsch, Chief Development Officer at 4SC, commented: "This is the first of three indications where we evaluate the potential of the pan-HDAC Inhibitor resminostat in cancer.
The initial clinical data of the SHELTER study is very encouraging as it supports our earlier Phase I results and leads us to believe this drug could be a viable option for HCC patients."
More information about the trial can be found on www.clinicaltrials.gov.
About Resminostat (4SC-201)
Resminostat or 4SC-201 is an oral pan-histone-deacetylase (HDAC) inhibitor. HDAC inhibitors epigenetically modify the chromatin structure of tumour cells to cause their differentiation and programmed cell death (apoptosis) and are therefore considered to offer a mechanism of action that has the particular potential to halt tumour progression and induce tumour regression.
Resminostat is currently in a Phase II study as a second line treatment for advanced hepatocellular carcinoma (HCC) and in a Phase II study in Hodgkin's lymphoma. In addition, a further Phase I/II study is planned in colon cancer, investigating resminostat as a second-line treatment option in patients with KRAS tumour mutations in combination with the FOLFIRI regimen. In a previous Phase I study with resminostat in patients with various cancer types, stable disease was achieved in over 50% of the patients, whilst the treatment was well tolerated and showed a positive, differentiating pharmacological profile to other drugs in this class.
About the SHELTER study
The "Shelter" study, "A proof-of-concept Phase II study to evaluate efficacy, safety and pharmacokinetics of 4SC-201 and of the treatment combination of Sorafenib plus 4SC-201 in patients with hepatocellular carcinoma exhibiting progressive disease under sorafenib treatment", is examining whether treatment with resminostat (4SC-201) alone or in combination with sorafenib (Nexavar®, the current standard of care in advanced HCC), can improve progression free survival or induces tumour responses in HCC patients. This two-arm, proof-ofconcept study is performed at oncology-experienced University hospitals in Germany.
In the first study arm, 15 patients are being treated with the maximum tolerated dose of the combination therapy which was determined through an initial dose-escalation part of the study, testing sorafenib in combination with resminostat. In the second study arm 15 patients discontinue sorafenib treatment prior to inclusion and then receive 600 mg of resminostat as a mono-therapy. Resminostat is orally administered, once daily, over five consecutive days, followed by a nine day treatment free period. In the combination arm sorafenib is administered every day. In both study arms, the resulting 14 day cycle for the treatment with resminostat (a "5 + 9" dosing schedule) is repeated until there is evidence of progressive disease or until the patient leaves the study for other reasons. The first two radiological tumour stagings will be performed after six and 12 weeks. Patients who experience a clinical benefit, e.g., a stabilization of their progressive disease or tumour regression, may extend the study treatment. Based on the data of the first 15 patients treated in each study arm, an optional extension phase comprising ten additional patients may be included into each study arm. The primary endpoint of the study is to determine the progression free survival rate (PFSR) after twelve weeks of study treatment.
The secondary endpoints include the analysis of time-to-progression (TTP), PFSR estimated at six weeks of treatment, overall survival, analysis of drug safety, tolerability, pharmacokinetics and the investigation of biomarkers.
About Hepatocelluar Carcinoma (HCC)
Hepatocellular carcinoma is the most prevalent form of liver cancer. HCC is the sixth most common cancer in the world and the third leading cause of cancer-related deaths globally.
HCC is most prevalent in Southeast Asia and is also very common in sub-Saharan Africa (an estimated 20 cases per 100,000 population by the World Health Organisation (WHO)). This is because in these geographies there is a high rate of Hepatitis B virus (HBV) infection, which may cause liver cancer as its genetic material disrupts the normal genetic material in the liver cells, thereby causing the liver cells to become cancerous.
Historically, North America and Western Europe, has had less incidence (