The first in human administration of NUC-3373 – a nucleotide analogue - has been given on the OCTRU Registered NuTide: 301 Trial. The trial, ran by the Oncology Clinical Trials Office and sponsored by the University of Oxford, is assessing the safety, pharamocokinetics and clinical activity of NUC-3373 in participants with advanced solid tumours.
Fluorouracil (5-FU) has been the backbone of therapy for a variety of different solid tumours for the last fifty years, however there is still a significant demand for more efficacious and better tolerated systematic therapies. NUC-3373 has been specifically designed to overcome the cancer resistance mechanism associated with 5-FU, it is likely to be more potent in tumour cells and therefore could be given at a lower dose to achieve efficacy with less off-target toxicity. Non clinical studies have demonstrated that NUC-3373 overcomes all the key cancer cell resistance mechanisms associated with 5-FU and capecitabine, generating high intracellular levels of the active FdUMP metabolite, resulting in a much greater inhibition of tumour cell growth.
Participants will be enrolled into Part 1 where NUC-3373 is administered on days 1, 8, 15 and 21 of a 4-week cycle, or be enrolled into Part 2 where NUC-3373 is administered on days 1, and 15 of a 4-week cycle. Participants may continue to receive treatment until their cancer progresses or until the study doctor feels the participant is not receiving any benefit from the study treatment. Once the RP2D's (the recommended dose that is determined to have the best benefit risk profile for the participants) have been determined in Parts 1 and 2, expansion cohorts will be opened to further participants to further explore safety and tolerability of these doses. It is anticipated up to 68 patients will be invited to participate in the trial in total.