Collaboration between the Oxford Cancer Network and industry to improve patient care
Significant demand for more efficacious and better tolerated systematic therapies, including novel agents and combination therapies.
Oxford has world-leading early phase clinical trials infrastructure, partnering with industry to foster translational research collaborations
NuCana, our industry partner, works to transform nucleoside analogs- some of the most widely prescribed chemotherapy drugs such as 5FU- using ProTide technology
The Old Guard?
5-FUis the backbone of therapy for a variety of different solid tumours and has been for the last fifty years
Produces the anti-cancer metabolite FUDR-MP
5FU hampered by thee key resistance mechanisms: insufficient target (TS) inhibition, extensive drug degradation by dihydropyrimidine dehydrogenase (DPD), and poor drug activation
Toxic metabolites pose risk of hand-foot syndrome
NUC3373 is designed to overcome resistance mechanisms associated with 5FU.
Non-clinical studies have shown 330x greater cytotoxicity in vitro than 5FU.
It shares the features common to all ProTides: the ability to enter cells without the need for membrane transporters; deliver the activated nucleotide analog; and avoid enzymatic degradation to potentially toxic compounds.
NUC-3373 can be infused over a much shorter time frame of 30 minutes – four hours compared to 46-hour continuous infusion required with 5-FU, due to it’s considerably longer half-life.
NUC-3373 and 5FU mechanisms of action
A two-part, phase 1 open label, dose escalation and expansion study to assess safety, pharmacokinetics and clinical activity of NUC3373 in participants with advanced solid tumours.
Purpose: To establish the recommended phase 2 dose (RP2D) for NUC-3373 and test these further in expansion cohorts