Date: 2013-07-25
Type of information: Treatment of the first patient
phase: 1-2
Announcement: treatment of the first patient
Company: Yakult Honsha (Japan) 4SC (Germany)
Product: resminostat
Action
mechanism: enzyme inhibitor/histone deacetylase 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. By causing structural changes to DNA, resminostat triggers a differentiation in tumour cells, can induce programmed cell death in cancer cells (apoptosis) and is able to halt tumour growth. Additionally, resminostat induces what is known as tumour cell 'sensitisation' to treatment with other anti-cancer drugs. This process can suppress or reverse certain tolerance mechanisms that tumour cells often develop against other cancer drugs. Supplementary treatment with an HDAC inhibitor such as resminostat can be expected to restore or significantly improve the efficacy of a previously administered cancer therapy; furthermore, combining resminostat and common cancer drugs right from the very beginning can also be expected to be effective in enhancing the success of the treatment.
Disease: non-small-cell lung cancer (NSCLC)
Therapeutic area: Cancer - Oncology
Country: Japan
Trial
details: The multi-centre and randomised study will investigate safety and efficacy of resminostat in combination with the cancer drug docetaxel vs. docetaxel alone in up to 118 patients in total with advanced, metastatic, or recurrent NSCLC who have previously received one platinum-based chemotherapy.The dose-escalation Phase I part of the study will assess safety, tolerability and pharmacokinetics as well as determine the maximum tolerated dose (MTD) and potential dose-limiting toxicities (DLT) of the resminostat/docetaxel combination in order to determine a recommended dose (RD) for the Phase II part.The randomised Phase II part will compare the efficacy of docetaxel alone - a standard chemotherapeutic regimen for NSCLC - with the combination therapy of resminostat and docetaxel in the enrolled NSCLC patients. In a 21 day cycle docetaxel (75 mg/m2 body surface area, administered intravenously on Day 1) will be given either as monotherapy in the control arm or in combination with resminostat (up to 600 mg/day, orally administered on Days 1-5) in the second study arm. Depending on the nature of potential side-effects observed, the dose of docetaxel may be reduced. The primary endpoint of the Phase II part is progression-free survival (PFS), secondary endpoints include response rate (RR), overall survival (OS), and safety.
Latest
news: * On July 25, 2013, 4SC AG , a discovery and development company of targeted small molecule drugs for cancer and autoimmune diseases, has announced that the first patient has been treated with resminostat in a Japan-based Phase I/II lung cancer (non-small-cell lung cancer, NSCLC) clinical study conducted by its exclusive Japanese partner Yakult Honsha.In 2011, 4SC granted an exclusive agreement to Yakult Honsha, the Japanese market leader in gastro-intestinal cancer therapeutics, for the development and commercialization of resminostat in Japan. In 2012 Yakult Honsha started the clinical development of resminostat in Japan with a Phase I study in solid tumours followed in 2013 by a Phase I/II study in first-line treatment of advanced liver cancer (hepatocellular carcinoma).Resminostat to date has been investigated in a broad clinical campaign comprising hepatocellular carcinoma, Hodgkin's Lymphoma, and colorectal cancer, with non-small-cell lung cancer now adding a third solid cancer indication to the programme.In the Phase II SAPHIRE trial in patients with advanced Hodgkin's Lymphoma (HL), resminostat in monotherapy has demonstrated substantial anti-tumour activity, with an overall response rate of 34% and a clinical benefit in 54% of the patients in a heavily pre-treated patient population together with very good safety and tolerability. In the Phase II SHELTER study resminostat has been evaluated as monotherapy and in combination with sorafenib as a second-line treatment in advanced HCC after proven radiological disease progression under first-line sorafenib therapy. Patients receiving the resminostat/sorafenib combination therapy showed a median overall survival of 8.1 months, a value to the company's best knowledge not reached in any study with a comparable second-line patient population. The resminostat/sorafenib combination therapy had shown a progression-free survival rate (PFSR) after 12 weeks of 70.0% and a median PFS of 5.4 months. The primary study endpoint was achieved ahead of schedule in both the combination and the monotherapy group. Furthermore, in the Phase I dose escalation part of the SHORE study, which has evaluated resminostat in combination with the chemotherapeutic FOLFIRI regimen in advanced CRC patients, positive results for safety and tolerability as well as promising signs of clinical activity of this combination has been published at the 2013 ASCO conference.4SC is currently in discussions with regulatory agencies and potential partners in order to prepare the next clinical steps to develop resminostat in combination with sorafenib in a pivotal programme in first-line HCC towards market approval.
