Corporate Banner
Satellite Banner
Pharma Outsourcing
Scientific Community
Become a Member | Sign in
Home>News>This Article

4SC Presents Summary of Biomarker and Patient Subgroup Analysis of Prognostic Factors

Published: Tuesday, October 01, 2013
Last Updated: Monday, September 30, 2013
Bookmark and Share
Further information about proposed role of biomarker ZFP64 in HCC tumour progression presented.

4SC AG has presented a detailed summary of results of a patient subgroup analysis of prognostic factors for overall survival and biomarkers in the Phase II SHELTER trial in advanced liver cancer (HCC).

The data will be presented in a poster presentation, 30 September 2013, from 2:00 PM - 4:30 PM (CEDT), at the ECCO 2013 (European Cancer Congress 2013) in Amsterdam). The poster will also be online at when the session begins at 2:00 PM (CEDT).

As previously reported, the SHELTER trial investigated the HDAC inhibitor resminostat both as a monotherapy and in combination with the cancer drug sorafenib (Nexavar®) as a 2nd line treatment of advanced HCC patients that had progressed under 1st line sorafenib therapy.

In the study, the combination of resminostat and sorafenib achieved a median overall survival (OS) of 8.1 months. This constitutes an additional gain of almost 3 months compared to the expected median OS of 5.2 months after progression on 1st line sorafenib therapy (see data from the 1st line HCC SHORE trial with sorafenib).

4SC is currently in preparation of pivotal clinical development plans for resminostat in combination with sorafenib in advanced HCC.

Dr Bernd Hentsch, Chief Development Officer of 4SC AG; comments: 'The identification of a number of most crucial patient characteristics relevant for survival expectations will now be supportive to guide the setup for our planned pivotal clinical development program with resminostat in advanced HCC. Furthermore, in conjunction with the application of our potentially predictive ZFP64 biomarker 4SC aims at developing resminostat into a personalized cancer medicine for this indication.'

Summary of the results presented at ECCO 2013 in further detail:
1) Selected baseline characteristics correlate with overall survival of advanced HCC patients in the SHELTER study

4SC reports results from the analysis of HCC patient baseline characteristics that appear to have an impact on overall survival in advanced HCC patients of the SHELTER study, treated with either resminostat monotherapy or in combination with sorafenib (Nexavar®). In the monotherapy arm, an overall good performance status of the patients (ECOG 0) and pre-treatment with a local ablative therapy (transarterial chemoembolization, TACE) correlated with a longer survival outcome. In the combination therapy arm in addition to ECOG 0 also the absence of liver cirrhosis (Child-Pugh A) and the absence of vascular invasion of the liver tumour was identified to correlate with a prolonged overall survival.

Notably, in both treatment arms the time interval between end of 1st line sorafenib therapy and 2nd line treatment start in the SHELTER study ('drug holidays') had no influence on the median OS of SHELTER patients. These and other factors will be considered as important enrollment and stratification criteria for the currently planned pivotal Phase III studies with resminostat in combination with sorafenib as a novel treatment option for advanced HCC.

2) High baseline expression of ZFP64 correlates with prolonged survival in cancer patients treated with resminostat; pharmacodynamic activity of resminostat (i.e. down-regulation of ZFP64 gene expression) confirmed; proposed role of ZFP64 in tumour progression further elaborated
In the search for suitable biomarkers that allow monitoring the pharmacodynamic activity of resminostat 4SC identified a set of genes that showed a robust and reproducible regulation of expression levels in response to resminostat within hours after drug exposure in peripheral blood of cancer patients. One of these highly regulated genes is the DNA binding transcription factor 'zinc-finger protein 64' (ZFP64). According to the current model of ZFP64 activity, this biomarker is expected to play a role in HCC tumour progression by promoting processes of liver inflammation and tumour progression in a dual way by (i) co-activation of NF-kB-mediated pro-inflammatory TLR signaling, and (ii) by co-activating the pro-tumourigenic Notch1 pathway. ZFP64 levels in peripheral blood samples of HCC patients can be conveniently determined by quantitative PCR technology. ZFP64 blood levels were rapidly reduced approx. 5-fold in comparison to baseline levels within 2-5 hours after drug intake, presumably reflecting a similar response at the patients' tumour site, also suggested by similar results obtained in vitro in a variety of cancer cell lines of different tumour origins.

Moreover, baseline expression of ZFP64 in HCC patients before the start of treatment proved to correlate in a statistically significant manner (p=0.04) with the achieved clinical outcome, i.e. higher baseline expression was indicative of a longer overall survival than lower baseline expression of ZFP64. High ZFP64 expression was observed in about 2/3 of the patients, resulting in a doubling of the median OS value in comparison to the 1/3 of patients with low baseline ZFP64 expression.

Importantly, this observation in advanced HCC patients of the SHELTER study treated with either resminostat monotherapy or in combination with sorafenib (Nexavar®) was confirmed in a second Phase II study (SAPHIRE) in advanced Hodgkin Lymphoma (HL) patients treated with resminostat monotherapy, indicating a potential predictive character of this biomarker for response to resminostat treatment and suggesting a common underlying biological background in certain tumours that might be more responsive to treatment with resminostat.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

4SC Receives Funding from the Eurostars Programme
Three-year research programme in cooperation with two other European epigenetics companies funded.
Saturday, October 03, 2015
4SC Strengthens Patent Protection for its Epigenetic Cancer Drug Candidate 4SC-202
A selective inhibitor of LSD1 and HDACs 1, 2, and 3 - in China.
Tuesday, August 18, 2015
4SC's Partner Yakult Honsha Starts Clinical Phase I Study in Pancreatic Tract Cancer Patients
Safety, tolerability and efficacy of resminostat in combination with S-1 chemotherapy will be investigated in various dosing schemes in order to determine dose regimen for potential subsequent Phase II trials in advanced pancreatic and/or biliary tract cancer.
Friday, June 26, 2015
4SC Presents Final Results from Phase I AEGIS Trial at ASCO
Daily dosage of oral, anti-mitotic Eg5 inhibitor shows good safety and tolerability.
Thursday, June 04, 2015
BEYOND RESEARCH Initiative of 4SC Discovery and CRELUX Reaches First Milestone
Compounds for inhibiting oxygen radicals and associated signalling pathways optimized for developing innovative therapies for degenerative diseases.
Tuesday, January 13, 2015
4SC Reports Positive Topline Data from Clinical Phase I Trial with 4SC-205
4SC-205 is the only oral inhibitor of the Eg5 kinesin protein in clinical development worldwide. Eg5 plays a crucial role in cell division and tumour growth.
Friday, December 12, 2014
4SC's Partner Yakult Honsha Completes Phase I Part of Clinical Study with Resminostat in NSCLC Patients
Phase I confirms safety and tolerability of resminostat/docetaxel combination in the planned dose regimen in Asian NSCLC patients.
Saturday, October 11, 2014
CRELUX and 4SC Discovery Awarded Research Grant
Project for identifying new bromodomain inhibitors initiated under the Munich m4 biotech cluster programme.
Thursday, July 24, 2014
4SC Hires Experienced Pharmaceutical Manager and Oncology Expert
Dr Erich Enghofer joins 4SC in the newly created position of Executive Vice President.
Friday, July 04, 2014
4SC Announces Positive Top Line Data from Clinical Phase I TOPAS Study
Company will present data from Phase I trial with epigenetic cancer drug 4SC-202 in patients with haematological tumours at ASCO.
Friday, May 30, 2014
4SC Discovery Receives EU Grant Worth EUR 450,000
Three-year research collaboration with the Medical Clinic of the University of Munich includes a project for identification and optimization of new compounds against a novel epigenetic target molecule.
Thursday, April 17, 2014
4SC Discovery Collaborates with Heidelberg University Hospital
The two-year R&D project is aimed at delivering a lead compound that can be brought to clinical development with the help of potential partners.
Friday, March 21, 2014
4SC Presents Results from Analysis of Biomarkers in Phase II SHELTER Trial in HCC
Oral presentation of detailed results at ILCA conference, 15 Sept. 2013, Washington D.C.
Friday, September 13, 2013
4SC's Partner Yakult Honsha Starts Clinical Phase I/II Study with Resminostat in NSCLC
The Phase I/II study will investigate safety and efficacy of resminostat/docetaxel combination vs. docetaxel alone as a novel treatment option for patients with advanced, metastatic, or recurrent NSCLC.
Thursday, July 25, 2013
4SC Expands Patent Protection for Epigenetic Anti-Cancer Compound
4SC AG announced that the company has significantly expanded international patent protection for 4SC-202 in the USA, China and Hong Kong.
Monday, July 15, 2013
Scientific News
Promising Drug Combination for Advanced Prostate Cancer
A new drug combination may be effective in treating men with metastatic prostate cancer. Preliminary results of this new approach are encouraging and have led to an ongoing international study being conducted in 196 hospitals worldwide.
Lucentis Effective for Proliferative Diabetic Retinopathy
NIH-funded clinical trial marks first major advance in therapy in 40 years.
Blocking the Transmission Of Malaria Parasites
Vaccine candidate administered for the first time in humans in a phase I clinical trial led by Oxford University’s Jenner Institute, with partners Imaxio and GSK.
First Therapy Appearing to Reverse Decline in Parkinson’s
An FDA-approved drug for leukemia improved cognition, motor skills and non-motor function in patients with Parkinson’s disease and Lewy body dementia in a small clinical trial, say researchers at Georgetown University Medical Center (GUMC).
Gene Therapy Staves Off Blindness from Retinitis Pigmentosa in Canine Model
NIH-funded study suggests therapeutic window may extend to later-stage disease.
Treatment for Rare Bleeding Disorder is Effective
Researchers in Manchester have demonstrated for the first time the relative safety and effectiveness of treatment, eltrombopag, in children with persistent or chronic immune thrombocytopenia (ITP), as part of an international duo of studies.
HIV Vaccine Human Trials Begin
Baltimore-based Institute has begun enrolling volunteers for initial phase 1 clinical trials.
New Therapy Reduces Symptoms of Inherited Enzyme Deficiency
A phase three clinical trial of a new enzyme replacement medication, sebelipase alfa, showed a reduction in multiple disease-related symptoms in children and adults with lysosomal acid lipase deficiency, an inherited enzyme deficiency that can result in scarring of the liver and high cholesterol.
Fixing Holes in the Heart Without Invasive Surgery
UV-light enabled catheter is a medical device which represents a major shift in how cardiac defects are repaired.
Atriva Therapeutics GmbH Develops Innovative Flu Drug
Highly effective against seasonal and pandemic influenza.
Scroll Up
Scroll Down

SELECTBIO Market Reports
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos