First-in-human Trial of PhOx430, a First-in-class Acetylglucosaminyltransferase V Inhibitor, in Advanced Solid Tumours

A standard 3 + 3 design will be followed. PhOx430 will be administered orally twice a day (bid), at a 12-hour interval, continuously in cycles of 21 days. At each dose level (DL), three patients will be included and the first patient will be observed for at least 21 days before enrolling the following two. Three additional patients will be enrolled at each DL if a DLT is observed in the first three patients. A maximum of 4 increasing Dose Levels are foreseen (10, 20, 40 and 70 mg/kg/day), and PhOx430 will be administered in two doses at a 12-hour interval.

The implementation of this cohort (Step 3) was decided by the Protocol Steering Committee (PSC) based on clinical and pharmacokinetic data obtained in Steps 1 and 2. Six patients will be enrolled, who will receive PhOx430 orally thrice a day (tid) at a -6-hour interval over 12 hours for 21 days, and then, starting from day 22, four times a day (qid) at a 4-hour interval over 12 hours, continuously in cycles of 21 days. PhOx430 will be taken in single doses of 1,200 mg to patients weighing ≥ 50 kg and of 600 mg to patients weighing \< 50 kg, with no requirement for a full or empty stomach. The first patient will be observed after treatment start for at least 21 days before enrolling the following two. After the third patient is observed for 21 days after treatment start, 3 additional patients will be enrolled without waiting time between them. If the daily dose tested with the tid schedule is not deemed safe, the flat dose will be tested twice a day (bid) at a 12-hour interval.