4SC to present at the virtual 10th World Congress of Melanoma and 17th EADO Congress
- RESMAIN study progress update
- MERKLIN 2 study progress update
Planegg-Martinsried, Germany, 15 April 2021 – 4SC AG (4SC, FSE Prime Standard: VSC) will attend and present at the virtual 10th World Congress of Melanoma and 17th EADO Congress, from the 15-17 April 2021. A summary of the key clinical trial updates are listed below:
- Trial in progress – Phase II trial evaluating Resminostat for maintenance treatment of patients with advanced stage (Stage IIB‑IVB) mycosis fungoides (MF) or Sézary Syndrome (SS) – RESMAIN study
- Trial in progress – Efficacy and safety of domatinostat in combination with avelumab in advanced unresectable/metastatic Merkel Cell Carcinoma patients progressing on anti-PD-(L)1 therapy – MERKLIN 2 study
The posters will be available on the 4SC homepage after the congress.
21 October 2020, First Patient Enrolled in MERKLIN 2 Study
12 October 2020, 4SC AG announces availability of a new publication on domatinostat
28 September 2020, 4SC AG announces publication of a new article on domatinostat
8 April 2020, FDA Accepts IND Application for MERKLIN 2 Study
31 January 2020, 4SC – Resminostat and RESMAIN Study Update
4SC AG is a clinical-stage biopharmaceutical company developing small-molecule drugs that 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 48 employees as of 31 December 2020 and is listed on the Prime Standard of the Frankfurt Stock Exchange (FSE Prime Standard: VSC; ISIN: DE000A14KL72).
Resminostat is an orally administered class I, IIb and IV histone deacetylase (HDAC) inhibitor that potentially offers an approach to treating different kinds of cancer. Resminostat demonstrated that it is well tolerated and can inhibit tumor growth and proliferation, cause tumor regression, and strengthen the body’s immune response to cancer.
Resminostat is currently being investigated in a pivotal study in cutaneous T-cell lymphoma (CTCL) as maintenance treatment by 4SC in Europe and by Yakult Honsha in Japan.
About cutaneous T-cell lymphoma (CTCL)
CTCL is a rare disease with approximately 5,000 patients being newly diagnosed in Europe each year. The disease arises from malignant transformation of T-cells, a specialized subgroup of immune cells, primarily affects the skin, but may ultimately involve lymph nodes, blood and visceral organs.
Currently, CTCL is not curable and treatment options for advanced-stage CTCL are limited. Although patients respond to the available treatment options, the duration of response is often short-lived and declines as the severity of the disease increases. The key therapeutic challenge in advanced-stage CTCL is therefore to make remissions more durable by halting disease progression and improving patient’s quality of life.
About the RESMAIN study – resminostat for maintenance treatment of CTCL
The pivotal RESMAIN study is being conducted at more than 50 clinical centers in 11 European countries and Japan. It will include up to 190 patients who suffer from advanced-stage cutaneous T-cell lymphoma (CTCL) that have achieved disease control with systemic therapy. The patients are randomized 1:1 to receive either resminostat or placebo. Patients who experience disease progression – while being on placebo – will be offered resminostat in an open label treatment arm.
The primary goal of the study is to determine whether maintenance treatment with resminostat prolongs progression-free survival and the key secondary objective is to prolong the time to symptom worsening (itching). A comprehensive biomarker program is also included in the study to ensure vital knowledge about the biological background of resminostat treatment in CTCL.
About the concept of maintenance therapy
The pivotal RESMAIN study is focused on patients with advanced-stage, incurable cutaneous T-cell lymphoma (CTCL). Such patients suffer from painful and itchy skin lesions resulting in disfigurement and a severely impaired quality of life. Furthermore, lymph nodes, blood or visceral organs can be involved. The current therapeutic options rarely provide long-lasting responses or stabilization of disease for meaningful periods, with most patients progressing within several months.
Resminostat is being evaluated as maintenance treatment – a unique innovative treatment approach in CTCL (Stadler et al., 2021) – intended to prolong the period patients are stable and not progressing. Furthermore, recent preclinical data suggests that resminostat has the potential to alleviate the itching in CTCL patients, thereby additionally improving their quality of life.
Domatinostat is an orally administered small molecule class I selective HDAC inhibitor. It strengthens the body’s own anti-tumor immune response. Domatinostat modulates the tumor and tumor microenvironment making it more visible to the immune system, susceptible to concomitant checkpoint inhibition, and facilitating the infiltration of immune cells into the tumor (Bretz et al., 2019).
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 (Tresckow et al., 2019). Signs of single-agent anti-tumor efficacy were observed; with one complete remission and one partial responder.
Besides its therapeutic potential as monotherapy, 4SC is focusing its development activities for domatinostat on 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 from which initial data was presented at ESMO 2019 (Hassel et al., abstract #5545).
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 currently being conducted by Prof. David Cunningham at The Royal Marsden NHS Foundation Trust in London, UK.
In addition, in a collaboration with the Netherlands Cancer Institute in Amsterdam, the DONIMI Study, a multicenter, investigator-sponsored phase Ib study, is conducted testing the combination of domatinostat, nivolumab and ipilimumab in high risk stage III melanoma in the neoadjuvant setting.
To advance this development program, 4SC has also signed a drug supply agreement with Merck KGaA for avelumab (anti-PD-L1 antibody) to conduct two Phase II clinical trials of domatinostat in combination with avelumab in advanced-stage Merkel cell carcinoma (MCC) patients progressing on previous anti-PD-(L)1 monotherapy (MERKLIN 2) and in metastatic treatment-naïve patients (MERKLIN 1).
About the MERKLIN 2 study – domatinostat + avelumab in advanced unresectable or metastatic Merkel cell carcinoma progressing on previous anti-PD-(L)1 therapy
The 4SC-sponsored MERKLIN 2 study (ClinicalTrials.gov identifier: NCT04393753) is a single-arm Phase II study investigating the combination of domatinostat and avelumab in advanced unresectable or metastatic Merkel cell carcinoma (MCC) progressing on previous anti-PD-(L)1 therapy. The primary objective is to investigate the anti-tumor efficacy of the combination evaluated by the Objective Response Rate (ORR). In addition, several secondary and exploratory endpoints comprising efficacy, safety and Health-related Quality of Life (HrQoL) will also be investigated.
The study is planned to enroll 40 patients in about 40 sites in Europe and the US. The Global Principal Investigator of MERKLIN 2 is Alexander von Akkooi, MD PhD, from the Netherlands Cancer Institute (NKI) Amsterdam. Avelumab (anti-PD-L1 antibody) is provided for the study by Merck KGaA under a drug supply agreement with 4SC.
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.