Date: 2013-06-03
Type of information:
phase: 1
Announcement: presentation of 2013 ASCO Annual Meetingheld in Chicago (USA)
Company: NuCana BioMed (UK)
Product: NUC-1031
Action
mechanism: NUC-1031 is a ‘ProTide’ based on a transformed gemcitabine reengineered to overcome the three key resistance mechanisms that seriously limit the effectiveness of gemcitabine in cancer patients. NUC-1031 delivers the partially activated agent, gemcitabine monophosphate, which is rapidly converted in the cell to the active agent,gemcitabine triphosphate (dFdCTP).ProTide technology enables the addition of a phosphoramidate moiety to the commonly used anti-cancer nucleoside analogues. This results in significantly more active agent being generated within the cancer cells, with much less metabolic degradation for superior efficacy and a more favourable safety profile.
Disease: advanced and progressing solid tumors
Therapeutic area: Cancer - Oncology
Country: UK
Trial details: This is a two-part Phase I, open label, dose-escalation, study of NUC-1031 as a single agent in patients with advanced solid tumours who have failed to respond to or who have relapsed after treatment with standard therapy. Non clinical studies have shown that NUC-1031 is more effective than gemcitabine because it is able to reach cancer cells by passive diffusion, is less easily degraded by the cancer cell, and delivers the monophosphate form of the active agent. The first part of the study is to determine recommended phase 2 dose by dose escalation and the second part is to explore preliminary anti-tumour activity. (NCT01621854 )
Latest
news: * On June 3, 2013, Nucana Biomed haspresented interim results from the Phase I study (ProGem1) of their novel ProTide, NUC-1031. Stable disease was achieved in over half of the patients who had a range of advanced, progressive cancers. Eleven heavily pre-treated patients with a wide range of advanced and progressing solid tumours were given up to 6 cycles of NUC-1031, each cycle lasting 4 weeks. In over half of the patients the cancers stopped growing and they were classified as having achieved stable disease. NUC-1031 was well tolerated with no unexpected adverse events. The pharmacokinetic data showed that NUC-1031 is rapidly converted in the cell into the active anti-cancer agent, gemcitabine triphosphate (dFdCTP), and achieves over 30 times higher intracellular levels of the active agent than gemcitabine. In addition, the ProTide is not broken down to gemcitabine and there are much lower levels of the potentially toxic uridine metabolite, dFdU.
The ProGem1 study will continue with an expansion cohort of patients to further assess the efficacy and safety profile of NUC-1031.
