Date: 2015-05-28
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Onxeo (France)
Product: belinostat
Action
mechanism: histone deacetylase inhibitor. Belinostat is a small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid tumors and hematologic malignancies either as a single agent, or in combination with other active anti-cancer agents, including carboplatin, paclitaxel, doxorubicin, idarubicin, cis-retinoic acid, azacytidine, 5-FU, etoposide and bortezomib for injection. HDAC inhibitors represent a new mechanistic class of anti-cancer therapeutics that target HDAC enzymes, and have been shown to: Arrest growth of cancer cells (including drug-resistant subtypes); induce apoptosis, or programmed cell death; promote differentiation; inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance when used in combination with other anti-cancer agents.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On May 28, 2015, Onxeo announced preclinical & clinical data from three studies supporting of the potential of belinostat in multiple orphan oncology indications. These results will be presented during a poster session and further reviewed during a separate poster discussion session, both on Sunday, May 31, at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, being held May 29-June 2 in Chicago, IL. Abstract e13581 – UGT1A1 genotype effects on PK, PD and toxicities of belinostat administered by 48 h continuous infusion. This study simultaneously evaluates the genotype effects of UGT1A1, a gene that plays a major role in the metabolism of belinostat, on the drug interactions and toxicities of belinostat in combination with other chemotherapies. In a Phase I trial of 25 patients with small cell lung cancer and other cancers of neuroendocrine origin and in a separate Phase I/II trial of 26 patients with thymic epithelial tumors, belinostat was administered by 48-hour continuous infusion across various dose levels (400-1000 mg/m2 per 24 hours) in combination with either cisplatin and etoposide, or cisplatin, doxorubicin and cyclophosphamide, respectively. Patients in both trials were genotyped for UGT1A1 variants associated with reduced function. The genotype UGT1A1 was associated with systemic exposure to belinostat and with incidence of toxicities in the Phase I trial, particularly at doses greater than 400 mg/m2 per 24 hours. The Phase I/II trial showed these associations to be less profound. Based on these results, genotype-based dose adjustments of belinostat may be desirable regardless of whether belinostat is used as a single-agent or in combination.
