4SC AG has announced positive top line data from its clinical Phase I TOPAS study with 4SC’s epigenetic cancer drug 4SC-202 in patients with advanced haematological tumours. 4SC-202, an oral small molecule inhibitor targeting WNT and Hedgehog (HH) signaling by specific inhibition of the epigenetic modifiers LSD1 and HDAC1, 2 and 3, was well tolerated, showed favorable pharmacokinetic properties and demonstrated promising signs of anti-tumour efficacy.
The main study phase has been completed for all patients, with one complete responder patient still remaining on follow-up study treatment. In detail, 4SC will present initial data from the study in a poster presentation at the upcoming annual ASCO (American Society of Clinical Oncology) meeting in Chicago.
The ASCO poster (Abstract No. 8559) will be available at http://4sc.de/product-pipeline/publications-posters/other when the presentation begins at 1:15 pm CDT (8:15 pm CEST) on 2 June 2014.
The first-in-man, open-label, dose-escalating, multi-centre, exploratory study evaluated safety, pharmacokinetics and pharmacodynamics of 4SC-202 in 24, heavily pre-treated, patients with advanced stages of haematological malignancies. The compound was studied in doses from 25 mg up to 400 mg total daily dose of 4SC-202 using various dosing schemes.
The drug showed promising signs of efficacy, both in terms of long-term disease stabilization of heavily pre-treated cancer patients and in terms of tumour shrinkage and objective radiological response. There was one complete remission (CR) and one partial remission (PR).
50% of patients (12 out of 24) had disease stabilization and time on study medication for more than 100 days, 13% were stabilized for over a year, and one patient could be stabilized for more than 2 years. The patient with the CR has been on the trial now for over 16 months, with both study treatment and CR still ongoing to date.
4SC-202 was generally safe and well tolerated in the doses tested. Due to the clean safety profile, no formal DLT (dose limiting toxicity) or MTD (maximum tolerated dose) could be determined. A recommended dose of 200 mg 4SC-202 once daily or twice daily in a 14+7 dosing scheme (14 days treatment, 7 days rest) was established.
The compound showed a favourable pharmacokinetic profile achieving potentially efficacious and well tolerated levels of 4SC-202 in patients. As for pharmacodynamics, the study showed promising biomarker responses including HDAC inhibition and a regulation of genes associated to the WNT signalling pathway in patient blood samples.
4SC will fully evaluate the data after final completion of the trial. In parallel, 4SC will investigate in particular WNT and HH related tumour indications for a possible Phase II development, and will also engage in talks with pharmaceutical partners interested in further development of the compound.
Enno Spillner, Chief Executive Officer of 4SC, said: “We are highly excited about the clinical Phase I top line results with our second epigenetic drug candidate 4SC-202. In the study 4SC-202 showed very good safety and highly promising signs of efficacy in heavily pre-treated patients with haematological tumours. We will now carry on our efforts on a Phase II development plan which we would like to pursue together with a potential pharmaceutical partner.”