4SC AG 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.
The multi-centre and randomized 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 randomized 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.
In 2011, 4SC 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.
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, HCC).
Enno Spillner, Chief Executive Officer of 4SC AG, said: 'We very much appreciate that our partner Yakult Honsha has started developing resminostat in NSCLC. After HCC and CRC, this is now the third solid cancer indication in which our new epigenetic drug has been introduced into clinical evaluation. Lung cancer is the leading cause of cancer-related mortality around the world, so we are excited to follow the development of resminostat in yet another indication of both high medical need and large market potential.'
Bernd Hentsch, Chief Development Officer of 4SC AG, added: 'There is intriguing evidence in the literature that inhibition of histone deacetylases (HDACs) may be effective in the treatment of lung cancer. Although many drugs have been tested in NSCLC, the medical need in this indication is still very high due to the heterogeneity of this group of cancers and its relative insensitivity to standard chemotherapy regimens. Therefore, the combination approach applied in this study again attempts to make use of the so far observed good ability of resminostat to be combined with a variety of other standard anti-tumor agents.'