4SC AG has announced updates on the clinical development of resminostat, its lead oncology drug, highlighting positive results from a Phase I study in advanced colorectal cancer (CRC) and promising biomarker data from Phase II trials in liver cancer (HCC) and Hodgkin lymphoma (HL).
Resminostat and FOLFIRI in Advanced CRC
The Phase I SHORE study investigated resminostat in combination with FOLFIRI (a chemotherapy regimen including 5-fluorouracil and irinotecan) as a second-line treatment for patients with advanced, KRAS-mutant CRC. The study's results, presented at the 2013 ASCO meeting, demonstrated that resminostat was safe and well-tolerated at doses up to 800 mg daily when combined with FOLFIRI. Side effects were generally mild to moderate, primarily gastrointestinal and hematological, consistent with those expected from FOLFIRI alone. Notably, no dose-limiting toxicities were observed, and the pharmacokinetic profile of resminostat remained favorable.
Beyond safety, the combination showed encouraging signs of clinical activity. Seven of fifteen evaluable patients experienced disease stabilization and were treated for at least 12 weeks, with a maximum duration of 33 weeks. These findings suggest that resminostat may enhance the efficacy of FOLFIRI in this patient population.
ZFP64 as a Predictive Biomarker
4SC also reported data from Phase II clinical trials (SHELTER in HCC and SAPHIRE in HL) identifying Zinc Finger Protein 64 (ZFP64) gene expression as a potential biomarker for resminostat treatment outcome. The analysis revealed a positive correlation between ZFP64 expression levels in peripheral blood cells at baseline and clinical benefit. Patients with higher baseline ZFP64 expression were more likely to achieve stable disease and experienced significantly longer overall survival compared to those with lower expression levels. These findings were consistent across both HCC and HL patient cohorts.
ZFP64 is a transcription factor and co-activator of Notch, a protein involved in cancer regulation. The identification of ZFP64 as a potential biomarker could enable personalized treatment strategies, selecting patients most likely to benefit from resminostat therapy. 4SC has filed a patent application to protect these findings and plans further studies to validate ZFP64's role in predicting resminostat response, particularly in first-line HCC treatment.
Future Directions for Resminostat
4SC is focusing on developing resminostat for market approval as a first-line treatment for advanced liver cancer (HCC). The company is developing a clinical plan for resminostat in combination with sorafenib as a first-line therapy for HCC and will discuss further development steps with potential partners and regulatory authorities in the EU and the US.
