First domatinostat combination data from Phase Ib/II SENSITIZE study presented at ESMO

First data release of domatinostat + pembrolizumab in anti-PD-1 refractory/ non-responding advanced cutaneous melanoma patients

Planegg-Martinsried, Germany, 30 September 2019 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced the publication of data from the first part of the Phase Ib/II SENSITIZE Study at the European Society for Medical Oncology Congress 2019 in Barcelona.

The SENSITIZE study ( identifier: NCT03278665) is enrolling up to 40 patients suffering from unresectable advanced-stage cutaneous melanoma who are refractory or non-responding to prior treatment with anti-PD-1 antibodies (checkpoint inhibitor).

In the first part of the study, three patient cohorts were treated at three different dose levels of domatinostat in combination with pembrolizumab.  At the time of data cut-off (July 15th, 2019, study still ongoing) a total of 23 patients were enrolled into the study:

  • Domatinostat in combination with pembrolizumab was safe and well tolerated
    • No increase in frequency or intensity of immune-related AEs observed
  •  Signs of efficacy were observed, including one patient with a confirmed partial response and 7 patients with stable disease (4 confirmed)
    • Indication of dose-dependency for domatinostat, with best results at the highest dose
  •  Preliminary biomarker analyses indicate a domatinostat-induced change in immunological tumor patterns

Jason Loveridge, Ph.D., CEO of 4SC: “Taking note of the favorable safety profile and first signs of clinical efficacy from the combination of domatinostat and pembrolizumab in this very hard to treat, anti-PD-1-refractory patient population is exciting and hugely encouraging. Especially since the preliminary tumor analyses indicates a confirmation of the proposed domatinostat-induced immunological effect.  As such, we believe that the combination of domatinostat with anti-PD-(L)1 will provide a valuable therapeutic option for patients that do not respond to checkpoint blockade alone and we now look forward to starting our MERKLIN study in a comparable group of patients with Merkel-cell carcinoma within the coming months.”

Related articles

11 July 2019, 4SC AG: Positive safety review of Phase Ib/II SENSITIZE study of domatinostat + pembrolizumab in melanoma

8 April 2019, 4SC AG: Domatinostat’s mode of action in Merkel cell carcinoma

6 February 2019, First patient enrolled in Phase II study EMERGE of domatinostat (4SC-202) in gastrointestinal cancer

About 4SC

4SC AG is a clinical-stage biopharmaceutical company developing small-molecule drugs that can target key indications in cancer with high unmet medical needs. 4SC’s pipeline is protected by a comprehensive portfolio of patents and currently comprises two drug candidates in clinical development: resminostat and domatinostat.

4SC aims to generate future growth and enhance its enterprise value by entering into partnerships with pharmaceutical and biotech companies and/or the eventual marketing and sales of approved drugs in select territories by 4SC itself.

4SC is headquartered in Planegg-Martinsried near Munich, Germany. The Company had 47 employees as of 30 June 2019 and is listed on the Prime Standard of the Frankfurt Stock Exchange (FSE Prime Standard: VSC; ISIN: DE000A14KL72).

About domatinostat

Domatinostat is an orally administered small molecule class I selective HDAC inhibitor. It strengthens the body’s own anti-tumor immune response, influences the tumor and tumor microenvironment, making the tumor more visible to the immune system and facilitates the infiltration of immune cells into the tumor.

Domatinostat has been investigated in a Phase I study in 24 heavily pretreated patients with several types of advanced hematologic cancers and was well tolerated. Positive signs of anti-tumor efficacy were also observed; with one complete remission (28 months) and one partial responder (8 months).

In addition to its therapeutic potential in cancer monotherapy, 4SC is evaluating domatinostat’s capacity as a partner in combination therapies, specifically in the immuno-oncology area. In this respect, 4SC initiated a Phase Ib/II study of domatinostat in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab in patients with advanced-stage melanoma. A second Phase II study of domatinostat in combination with the anti-PD-L1 checkpoint inhibitor avelumab in patients with advanced-stage microsatellite-stable gastrointestinal cancer is conducted by Prof. David Cunningham of The Royal Marsden NHS Foundation Trust (London, UK).

As soon as results from the aforementioned trials will be available, 4SC plans to advance domatinostat into a number of studies in combination with a checkpoint inhibitor, including in patients with advanced Merkel-cell carcinoma (MCC).

About the SENSITIZE study – Domatinostat (4SC-202) + pembrolizumab for treatment of melanoma

The SENSITIZE Phase Ib/II study ( identifier: NCT03278665) was opened for recruitment from September 2017 and is conducted at 6 certified skin cancer centers in Germany. It will enroll up to 40 patients suffering from unresectable advanced-stage cutaneous melanoma who are refractory or non-responding to prior treatment with anti-PD-1 antibodies (checkpoint inhibitors). In the first part of the study, 3 cohorts will be treated at different dose levels of domatinostat in combination with pembrolizumab. In the second part, additional patients will be treated with the recommended dosing regimen defined in the first part of the study.

The primary goal of the study is to determine the safety and tolerability of domatinostat in combination with pembrolizumab and key secondary endpoints aim to assess the anti-tumor activity of the combination treatment. Additionally, the study will investigate changes in key immunological biomarkers to better understand how domatinostat renders patients more susceptible to treatment with checkpoint inhibitors. 4SC plans to present top-line data from the first part of the study at ESMO in 2019.

Forward-looking information

Information set forth in this press release contains forward-looking statements, which involve risks and uncertainties. The forward-looking statements contained herein represent the judgement of 4SC as of the date of this press release. Such forward-looking statements are neither promises nor guarantees but are subject to a variety of risks and uncertainties, many of which are beyond 4SC’s control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. 4SC expressly disclaims any obligation or undertaking to release any updates or revisions to any such statements to reflect any change in its expectations or any change in events, conditions or circumstances on which any such statement is based.

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