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

4SC Reports Positive Data from Clinical Phase I trial with 4SC-205 in Cancer Patients

Published: Thursday, March 28, 2013
Last Updated: Wednesday, March 27, 2013
Bookmark and Share
All primary objectives of the clinical study achieved.

4SC AG has announced clinical data of the Phase I 'AEGIS' trial with the anti-cancer compound 4SC-205 in tumour patients. All primary study objectives were achieved. A comprehensive safety and tolerability profile of 4SC-205 was established.

As well as ascertaining the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs), an excellent pharmacokinetic profile of the oral compound was established. In addition, the analysis of pharmacodynamic biomarkers demonstrated the intended mode of action.

The study data and new preclinical findings about the therapeutic target warrant further clinical evaluation of 4SC-205 in cancer patients. The Company, therefore, has decided on a study amendment, which will evaluate a new, adapted dosing scheme.

The first patient has now been treated according to the new scheme. 4SC-205 inhibits specifically the human kinesin spindle protein Eg5 which has been shown to play a crucial role in cell division (mitosis) and, therefore, in tumour growth.

To the Company's best knowledge, 4SC-205 is the only orally available Eg5 inhibitor in clinical development, worldwide.

Study design and positive results
The 'first-in-man', two-centre, dose-escalating Phase I study ('AEGIS' study) investigated safety, tolerability, pharmacokinetics, and pharmacodynamics of 4SC-205 in 46 patients with advanced solid tumours.

In two treatment cycles, each over three weeks, patients were treated with ascending oral doses of 4SC-205 in order to establish the MTD and potential DLTs.

Patients were treated in two different dose schedules: in the first dose schedule, patients received once-weekly dosing on days 1 and 8 of each cycle; in a second dose schedule patients received twice-weekly dosing on days 1, 4, 8 and 11 of each cycle.

In patients receiving once-weekly dosing, the MTD was established at the 150 mg dose level; in patients receiving a twice-weekly dosing, an MTD of 75 mg was established.

DLTs were reached at the treatment doses of 200 mg with once-weekly dosing and of 100 mg with twice-weekly dosing. Main side effects at DLT level were neutropenia and stomatitis of grade 3-4.

Moreover, 4SC-205 showed an excellent pharmacokinetic profile with a dose proportional increase of exposure and an elimination half-life of about 10 hours providing the basis for effective dosing schedules since the biological activity of the compound could be demonstrated via biomarker analysis of patients' skin biopsy samples.

Here, a dose dependent accumulation of cells arrested in cell division could be observed. Thus, 4SC-205 effectively exhibits the anticipated mode of action - inhibition of cell division (mitosis) - at clinically tolerated doses.

AEGIS study amendment
The clinical findings generated to date from this trial as well as new preclinical data about the therapeutic target and distribution of 4SC-205 in tissue, strongly support further clinical investigation of the compound applying an additional treatment schedule. The study has, therefore, been amended in order to investigate a new and innovative dosing scheme of 4SC-205 for the first time in cancer patients.

According to the amendment, another 9 to 12 eligible patients are expected to be enrolled in the trial. Following recent approval of the amendment by authorities, the first patient has now been treated. The results of the amended AEGIS study protocol are expected for mid 2013.

Dr Ulrich Dauer, Chief Executive Officer of 4SC, commented: 'We are pleased that in our AEGIS trial we have achieved all primary endpoints so far. 4SC-205 inhibits with high specificity an intriguingly interesting therapeutic target in anti-cancer treatment, the Eg5 protein, which plays a central role in cell mitosis and tumour growth. The encouraging biomarker response to 4SC-205 as shown in the study and new preclinical findings regarding the therapeutic target, make a strong case to further study our drug candidate in a new, highly innovative dosing scheme. This is expected to form a basis for the further evaluation of the compound in Phase II development. The fact that 4SC-205 is the only oral Eg5 inhibitor in clinical development is a strategic strength that facilitates the possibility to further explore alternative and enhanced dosing schemes.'


Further Information

Join For Free

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 3,000+ scientific posters on ePosters
  • More than 4,400+ 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 TechnologyNetworks.com 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 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 Gives Update on the Clinical Development of its Lead Cancer Compound Resminostat
Data from completed Phase I part of SHORE study confirms the safety of the resminostat FOLFIRI combination and showing encouraging signs of clinical benefit
Thursday, May 30, 2013
4SC to Present Biomarker Data for Cancer Drug Resminostat at EHA
Data from Phase II SAPHIRE trial in Hodgkin’s lymphoma presented at EHA meeting in Amsterdam.
Monday, June 18, 2012
Scientific News
Potential “Good Fat” Biomarker
New method to measure the activity of energy consuming brown fat cells could ease the testing weight loss drugs.
Computational Model Finds New Protein-Protein Interactions
Researchers at University of Pittsburgh have discovered 500 new protein-protein interactions (PPIs) associated with genes linked to schizophrenia.
New Insights into Gene Regulation
Researchers have solved the three-dimensional structure of a gene repression complex that is known to play a role in cancer.
Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Soy Shows Promise as Natural Anti-Microbial Agent
Soy isoflavones and peptides may inhibit the growth of microbial pathogens that cause food-borne illnesses, according to a new study from University of Guelph researchers.
Potential Target for Revolutionary Antibiotics
An international team of including the Lomonosov Moscow State University researchers discovered which enzyme enables Escherichia coli bacterium (E. coli) to breathe.
DNA Barcodes Gone Wild
A team of researchers at University of Toronto’s Donnelly Centre and Sinai Health System’s Lunenfeld-Tanenbaum Research Institute (LTRI) has developed a new technology that can stitch together DNA barcodes inside a cell to simultaneously search amongst millions of protein pairs for protein interactions.
Biomarkers for Profiling Prostate Cancer Patients
Exiqon A/S has announced the publication of validation of prognostic microRNA biomarkers for the aggressiveness of prostate cancer in independent cohorts.
Grant to Fund Million Peaks Project
The European Research Council (ERC) has awarded a prestigious Advanced Grant to Prof. Peter Schoenmakers, Prof. Albert Polman and Prof. Huib Bakker, all three of whom work at the University of Amsterdam (UvA).
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Scroll Up
Scroll Down
SELECTBIO

Skyscraper Banner
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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!