* 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 (https://www.4sc.com/) after the congress.

Related articles

21 October 2020, First Patient Enrolled in MERKLIN 2 Study (https://www.4sc.com/news/first-patient-enrolled-in-merklin-2-study/)

12 October 2020, 4SC AG announces availability of a new publication on domatinostat (https://www.4sc.com/news/4sc-ag-announces-availability-of-a-new-publication-on-domatinostat/)

28 September 2020, 4SC AG announces publication of a new article on domatinostat (https://www.4sc.com/news/4sc-ag-announces-publication-of-a-new-article-on-domatinostat/)

8 April 2020, FDA Accepts IND Application for MERKLIN 2 Study (https://www.4sc.com/news/fda-accepts-ind-application-for-merklin-2-study/)

31 January 2020, 4SC – Resminostat and RESMAIN Study Update (https://www.4sc.com/news/4sc-resminostat-and-resmain-study-update/)

27 September 2019,Key resminostat scientific data to be presented at EORTC-CLTF meeting in Athens (https://www.4sc.com/news/key-resminostat-scientific-data-to-be-presented-at-eortc-cltf-meeting-in-athens/)

28 January 2019, 4SC’s pivotal RESMAIN study of resminostat in CTCL receives second positive safety review (https://www.4sc.com/news/4scs-pivotal-resmain-study-of-resminostat-in-ctcl-receives-second-positive-safety-review/)

Further information

About resminostat

Resminostat (http://www.4sc.com/product-pipeline/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 (https://clinicaltrials.gov/ct2/show/NCT02953301) 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 (https://clinicaltrials.gov/ct2/show/NCT02953301) 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.

About domatinostat

Domatinostat (http://www.4sc.com/product-pipeline/4sc-202/) 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.

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.