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-FU is 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
Protide transformations
- 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
Study
- 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
Trial Information
Chief Investigator
