|Patients (enrolled to date)||36|
|Median Age||60 (range 21-78)|
|Median Prior Chemotherapy Regimens||3 (range 1-6)|
NUC-3373 is currently being evaluated in a Phase I clinical study of patients with advanced solid tumours for which we reported interim data in September 2017. Key interim findings include a favourable plasma half-life of 9.7 hours compared to just 8-14 minutes for 5-FU; the ability to completely deplete the intracellular pool of dTMP, along with undetectable levels of the toxic metabolite dhFU.
|Plasma half-life||9.7 Hours||8-14 minutes|
|FUDR-MP (in PBMCs)||Detected (dose proportional)||Undetected(*)|
|Thymidylate Synthase inhibition||Strong||Weak|
|Intracellular levels of dTMP||Depleted||No change|
|Toxic metabolite (dhFU)||Levels not clinically significant||High levels|
To date, 36 patients, all with metastatic cancer, have been enrolled in the study, with 29 patients receiving NUC-3373 on a weekly schedule on days 1, 8, 15 and 22 of a 28-day cycle at doses ranging from 125 mg/m2 to 1,500 mg/m2 and 7 patients receiving NUC-3373 on an alternate-week, or fortnightly, schedule on days 1 and 15 of a 28-day cycle at doses ranging from 1,500 mg/m2 to 1,875 mg/m2.
Both dosing regimens were observed to be well tolerated with no unexpected adverse events (AEs) or accumulative toxicity. Importantly, no patients developed hand-foot syndrome, which is a debilitating side effect associated with fluoropyrimidine therapy. In addition, NUC-3373 has a plasma half-life of 9.7 hours compared to the 8 to 14-minute plasma half-life of 5-FU. As a result, NUC-3373 can be infused over a much shorter time frame of 30 minutes to four hours compared to the 46-hour continuous infusion required with 5-FU.
Notably, three patients achieved Stable Disease after treatment, with responses lasting more than nine months at the time of data cutoff on September 25, 2018: