4SC AG has announced that the first patient has been treated with resminostat in a Japan-based Phase I clinical study conducted by 4SC's exclusive Japanese partner Yakult Honsha. The multi-centre open-label study will investigate safety, pharmacokinetics, biomarkers and efficacy of various dose regimens of resminostat in monotherapy or in combination with the S-1 chemotherapy in up to 44 Japanese patients with advanced pancreatic or biliary tract cancer. The main goal of the study is to determine the recommended regimen for subsequent Phase II trials in these indications.
In Part 1 of the study, dose limiting toxicities (DLTs) of various dose regimens of resminostat in monotherapy and the resminostat/S-1 combination therapy will be determined in up to 24 patients. In Part 2, the tolerability and safety of the regimen/s selected in Part 1 will be further evaluated in 20 additional patients in order to determine the recommended regimen/s for subsequent Phase II studies. Furthermore, the study will investigate pharmacokinetics, biomarkers and efficacy criteria including best overall response, progression-free survival (PFS), and overall survival (OS).
The overall development rationale behind the study is to test the epigenetic agent resminostat in further gastrointestinal indications and in particular in combination with the S-1 chemotherapy, which is approved for the treatment of pancreatic and biliary tract cancer in Japan. S-1 contains a prodrug of the chemotherapeutic agent 5-FU.
Resminostat has already been tested clinically in a Phase I study in combination with the 5-FU-based FOLFIRI chemotherapy regimen in Western patients with colorectal cancer. The administration of resminostat in combination with the standard FOLFIRI regimen was well tolerated without any dose limiting toxicity. Moreover in preclinical models, resminostat has shown first positive results in pancreatic and biliary tract cancer.
Enno Spillner, Chief Executive Officer of 4SC AG, said: "We very much appreciate that our partner Yakult Honsha has started developing resminostat in combination therapy with an established cancer drug in additional two gastrointestinal solid cancer indications in Japan. There is high unmet medical need in both pancreatic and biliary tract cancer. These new indications are a perfect match to the ongoing Phase II trials by Yakult investigating resminostat in combination therapies in the indications liver cancer (HCC) and non-small-cell lung cancer (NSCLC). While Yakult is evaluating resminostat in a number of mostly gastrointestinal solid cancer indications in Asian patients, 4SC intends to focus, as the immediate next step, on developing resminostat in the heamatological indication of CTCL in Europe where we also see a high medical need and an attractive opportunity for a fast-to-market option for resminostat. We are currently preparing a European Phase II study in CTCL."