Tovecimig (CTX-009)

The phase 1 first-in-human monotherapy study in South Korea used a 3 plus 3 design across nine dose levels from 0.3 to 17.5 mg/kg given every 2 weeks; no dose-limiting toxicity occurred and the maximum tolerated dose was not reached. The starting dose of 0.3 mg/kg was derived from a no observed adverse effect level of 10 mg/kg in cynomolgus monkeys, converted to a human equivalent dose with a safety factor of 10. All responses in the phase 1 study occurred at dose levels above 10 mg/kg and all confirmed responses at 10 mg/kg or 12.5 mg/kg. The dose taken into the phase 2 study in biliary tract cancer and into COMPANION-002 is 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle, given with paclitaxel 80 mg/m2 on days 1, 8 and 15. Population pharmacokinetic simulations indicate that a fixed dose of 700 mg gives exposure comparable with 10 mg/kg, and that 15 mg/kg every 3 weeks gives an average steady-state concentration comparable with 10 mg/kg every 2 weeks. No labeled dose, dose-modification table, or dosing recommendation for organ impairment exists.