Date: 2014-04-07
Type of information: Initiation of preclinical development
phase: 1
Announcement: presentation of results at the annual meeting of the American Association for Cancer Research (AACR) in San Diego, CA.
Company: OncoEthix (Switzerland)
Product: OTX015
Action
mechanism: Bromodomain inhibitor. This synthetic small molecule is an inhibitor of BET bromodomain proteins 2/3/4. These proteins are considered potential cancer targets, as they play a pivotal role in regulating the transcription of growth-promoting and cell cycle regulators, especially c-MYC.
Disease:
Therapeutic area: Cancer - Oncology
Country: France, Italy, Switzerland
Trial
details: The design of the Phase I trial will seek to determine the optimum dosing regimen for OTX015, and to provide further safety, pharmacokinetic and pharmacodynamic data. The study will be conducted in two parts: dose escalation, followed by expansion cohorts. In the first part, dose escalation and determination of the recommended dose will be performed independently in two parallel subsets of patients: patients with acute leukemia and patients with other hematologic malignancies. Once the optimum dosing regimen has been determined, the second part of the study will further assess safety, pharmacokinetics, pharmacodynamics and clinical activity in disease specific cohorts of at least 12 patients treated at the recommended dose.
Latest
news: * On April 7th 2014, OncoEthix, a Swiss-based specialist in oncology drug development, has announced that the interim results from its ongoing Phase I clinical trial of OTX015, in patients with hematologic malignancies, were presented at the annual American Association of Cancer Research (AACR) meeting in San Diego. The interim data demonstrates meaningful clinical activity and excellent tolerance for patients on a daily oral dose of OTX015, a novel first-in-class synthetic small molecule inhibitor of BET bromodomain proteins 2/3/4. These proteins are considered potential cancer targets, as they play a pivotal role in regulating the transcription of growth-promoting and cell cycle regulators, especially c-MYC. * On January 31, 2013, OncoEthix has announced progress in its Phase I study of OTX015, a novel BET bromodomain inhibitor, with the first dosing of a patient. Phase I trials of OTX015 in healthy volunteers have already been completed. The design of the Phase I trial will seek to determine the optimum dosing regimen for OTX015, and to provide further safety, pharmacokinetic and pharmacodynamic data. Study centers are now open at five reference sites in Europe [France, Italy and Switzerland] selected for investigators having extensive hematology and clinical pharmacology expertise.Preclinical data have shown that OTX015 treatment of acute leukemia (both cell lines and patients’ cells), various subtypes of lymphoma and multiple myeloma cell lines induces potent anti-proliferative effects associated with cell cycle arrest, cellular senescence or apoptosis. Oncoethix in-licensed OTX015 from Mitsubishi Tanabe Pharma Corporation in March 2012 following completion of Phase I clinical studies in healthy volunteers.
Following on from Phase Ia trials in healthy volunteers, the primary objective of the Phase Ib, multi-centre, clinical study was to determine the maximum tolerated dose (MTD) of OTX015 that could be administered to patients with acute leukaemia or other hematologic malignancies. Patients were dosed at 10, 20, 40, or 80 mg once daily (QD) or 40 mg twice daily (BD). This two strata Phase 1 study, which started in January 2013, was also designed to provide further safety, pharmacokinetic and pharmacodynamic data.
The OTX015 interim Phase Ib results showed linear pharmacokinetics and excellent tolerance in both acute leukaemia and patients with other hematologic malignancies at once daily 80 mg doses. For acute leukaemia patients the MTD was not reached at 80 mg QD or 40 mg BID. Likewise, the MTD was not reached at 80 mg QD for patients with other hematologic malignancies, but in contrast this was exceeded at 40 mg BID in these patients, suggesting schedule-dependent toxicity.
The company is now performing dose escalation studies and expanding the patient cohorts to complete this Phase I clinical study.
