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Clinical Trials

Date: 2017-01-24

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 2017 Gastrointestinal Cancers Symposium in San Francisco

Company: Yakult Honsha (Japan) 4SC (Germany)

Product: resminostat (oral pan-histone deacetylase (HDAC) inhibitor)

Action mechanism: histone deacetylase inhibitor (HDAC inhibitor). Resminostat is an oral pan-histone-deacetylase (HDAC) inhibitor with an innovative, epigenetic mechanism of action that enables this compound to be deployed as a novel, targeted tumour therapy for a broad spectrum of oncological indications, particularly in combination with other anti-cancer drugs. Like other epigenetic therapies, resminostat has been shown to modify transcription of genes in cancer cells and, thereby, to reprogram the phenotypes of such cancer cells. Resminostat is therefore assumed to be able to halt tumour progression and induce tumour regression. Furthermore, due to its epigenetic mode of action resminostat is supposed to develop additional synergetic effects when combined with classical cancer therapies and thus also fight the development of tumour cell resistance. In April 2011, 4SC has granted an exclusive license to Yakult Honsha, the Japanese market leader in gastro-intestinal cancer therapeutics, for the development and commercialization of resminostat in Japan.

Disease: hepatocellular carcinoma (HCC)

Therapeutic area: Cancer - Oncology

Country: Japan, Republic of Korea

Trial details: The purpose of this study is to assess efficacy and safety in combination of resminostat and sorafenib in Asian patients with advanced hepatocellular carcinoma previously untreated with systemic chemotherapy.(NCT02400788)

Latest news:

  • • On January 24, 2017, 4SC announced that the study investigators presented the detailed scientific study analysis (abstract #252) from the multi-center, randomized, 170 patient Phase II study conducted by 4SC's cooperation partner Yakult Honsha in Japan and South Korea at the 2017 Gastrointestinal Cancers Symposium in San Francisco, USA. The study evaluated 4SC's epigenetic cancer drug resminostat in combination with sorafenib compared to sorafenib monotherapy as first-line treatment in patients with advanced liver cancer.  Although the primary endpoint was not reached in this study, the results of the subgroup analysis suggest a population-specific effect for the combination therapy, especially in one which is HBV+. This warrants the further development of this combination as first-line therapy in a well-defined subset of patients with advanced hepatocellular carcinoma.
  • • On October 5, 2016, 4SC and its development partner Yakult Honsha retrospectively analyzed the data of the randomized, multicenter Phase II study, conducted by Yakult Honsha in Japan and South Korea. The study investigated the effect of 4SC's epigenetic cancer drug resminostat in combination with the standard of care drug sorafenib compared with sorafenib monotherapy as a potential novel first-line treatment for patients with advanced liver cancer (hepatocellular carcinoma, HCC). Treatment with resminostat in combination with sorafenib demonstrated a substantial overall survival (OS) benefit compared with sorafenib monotherapy in a large subgroup comprised of 84 patients (50 % of all patients in the study) with a greater than median platelet count at study entry. Based on these results, 4SC and Yakult are currently discussing their plans for continued clinical development of resminostat. The results of the study will be published by Yakult Honsha and the investigators at an upcoming scientific conference.
  • • On May 27, 2016, 4SC AG announced that its Japanese partner Yakult Honsha has completed the randomized Phase II part of a clinical Phase I/II study which evaluates 4SC’s epigenetic cancer compound resminostat in combination with the cancer drug sorafenib as a potential novel first-line therapy of Asian patients in Japan and South Korea with advanced liver cancer. After successfully completing a Phase I safety study with resminostat in Japanese patients with advanced solid tumors in May 2014, Yakult Honsha initiated the Phase I/II study in patients with hepatocellular carcinoma, a cancer with high medical need and very limited therapeutic options, which has a particularly high incidence in Japan. In the Phase II part in 170 Asian patients with advanced HCC, resminostat in combination with sorafenib as first-line therapy in hepatocellular carcinoma did not meet the primary endpoint of statistically significant prolonged time to disease progression (TTP) compared to sorafenib monotherapy. Based on the result of the Phase II part, Yakult Honsha will not conduct a pivotal study of resminostat/sorafenib combination as first-line treatment of HCC in all-comer patients. However, patients with high expression levels of the ZFP64 biomarker at baseline seem to have longer TTP in the sorafenib/resminostat combination therapy when compared with sorafenib monotherapy. Yakult Honsha is now analyzing the results in more detail. Other ongoing as well as planned clinical trials, and in particular 4SC’s anticipated Phase II CTCL trial in the EU, will not be affected.
  • • On September 23, 2014, 4SC announced that its Japanese partner Yakult Honsha has successfully completed the Phase I part and initiated the randomised Phase II part of a clinical Phase I/II study which evaluates 4SC's epigenetic cancer compound resminostat in combination with the cancer drug sorafenib as a potential novel first-line therapy of advanced Asian hepatocellular carcinoma (HCC) patients. In the dose escalation Phase I part in 9 Asian patients with advanced HCC, the resminostat/sorafenib combination proved to be safe and well tolerated. Based on the result of the Phase I part, the multi-centre randomised Phase II part of the trial has been started. It will compare the efficacy of the resminostat/sorafenib combination with the current HCC standard therapy of sorafenib as a first-line treatment in up to 140 patients with advanced HCC. The primary endpoint will be time-to-progression (TTP). Secondary endpoints are, inter alia, overall survival (OS), progression-free survival (PFS) and safety. The study will also evaluate the ZFP64 biomarker. All patients enrolled have to be previously untreated with systemic chemotherapy.

Is general: Yes