First Patient Enrolled in TURANDOT Study Evaluating Domatinostat in the Neoadjuvant Setting in Urothelial Carcinoma
Combination of domatinostat (HDAC inhibitor) and checkpoint inhibition to be investigated in urothelial carcinoma (TURANDOT study)
Planegg-Martinsried, Germany, 30. September 2021 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced that the Netherlands Cancer Institute (NKI) in Amsterdam has enrolled the first patient in TURANDOT – a multicenter, investigator-sponsored phase 1b study conducted by Dr. Michiel van der Heijden at the NKI, Amsterdam, the Netherlands, testing the combination of domatinostat and checkpoint inhibition in stage II-III resectable urothelial carcinoma in the neoadjuvant setting.
The TURANDOT study investigates safety, feasibility and proof-of-principle of the addition of domatinostat to pre-operative immune checkpoint inhibition (CPI) with nivolumab and ipilimumab. Urothelial cancer patients will be included that are diagnosed with resectable stage II-III disease and PD-L1 status will determine the treatment cohort. Within each cohort, patients will be randomized to receive CPI + domatinostat or CPI alone. The primary endpoint is feasibility of neo-adjuvant domatinostat + nivolumab +/- ipilimumab defined by percentage of patients who are able to have surgical resection within 12 weeks. Main secondary endpoints are efficacy endpoints such as pathological complete response (pCR), relapse-free survival (RFS) and overall survival (OS), and safety. In addition, the study comprises a comprehensive translational research program.
Jason Loveridge, Ph.D., CEO of 4SC: “Such a very rapid start to TURANDOT signals a high level of interest in both the neoadjuvant setting as well as the combination of domatinostat and checkpoint blockade in this population and we look forward to further patients enrolling in 2021.”
Dr. Michiel van der Heijden, NKI: “We are excited to start recruitment into the TURANDOT study investigating the scientifically well-rationalized combination of domatinostat and checkpoint inhibition. Neoadjuvant treatment is currently a major focus of clinical research in oncology and already has its place in the treatment of urothelial carcinoma – nevertheless there remains a high unmet medical need to improve treatment options to reduce the number of relapses after surgery. Innovative immunotherapy combinations, as tested in TURANDOT, are a promising approach to improve clinical outcome.”
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 48 employees as of 31 March 2021 and is listed on the Prime Standard of the Frankfurt Stock Exchange (FSE Prime Standard: VSC; ISIN: DE000A3E5C40).
About the Netherlands Cancer Institute
The Netherlands Cancer Institute (NKI) is among the world’s best comprehensive cancer centers, combining innovative fundamental, translational, and clinical research with dedicated patient care. Our research themes are Fundamental Research, Immunotherapy, Precision Oncology, Image-guided Therapy and Survivorship. Our research institute gratefully acknowledges funding from the Dutch Ministry of Health, Welfare and Sport, the Dutch Cancer Society, and individual donors. For more information please visit our websites www.nki.nl and www.avl.nl.
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) and updated data at ASCO 2021.
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 and the TURANDOT Study are conducted. The DONIMI Study is a multicenter, investigator-sponsored phase Ib study testing the combination of domatinostat, nivolumab and ipilimumab in high-risk stage III melanoma in the neoadjuvant setting. The TURANDOT Study is a multicenter, investigator-sponsored phase Ib study testing the combination of domatinostat, nivolumab and ipilimumab in resectable stage II-III urothelial cancer 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).
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.