A phase I dose-escalation and pharmacokinetic study of a micellar nanoparticle with entrapped docetaxel (CPC634) in patients with advanced solid tumours.

Background: CPC634 is docetaxel entrapped in core-cross linked polymeric micelles. In preclinical studies, CPC634 demonstrated enhanced pharmacokinetics and improved therapeutic index. This phase I dose escalation study is the first-in-human study with CPC634.

Methods: adult patients with advanced solid tumours received CPC634 intravenously either 3-weekly (Q3W) (part 1, dose range 15-100 mg/m), 2-weekly (Q2W) (part 2, 45 mg/m) or Q3W with dexamethasone premedication (part 3, 60 mg/m).

Results: thirty-three patients were enrolled. Skin toxicity was dose limiting (DLT) at ≥60 mg/m in part 1 and at 45 mg/m in part 2 and was the most common CPC634 related grade ≥ 3 adverse event (24%). With dexamethasone premedication no DLTs were observed at 60 mg/m Q3W. CPC634 exhibited a dose-proportional pharmacokinetic profile. At 60 mg/m, the plasma area under the curve was 4067.5 ± 2974.0 ng/h/mL and the peak plasma level 217.3 ± 91.9 ng/mL with a half-life of 39.7 ± 9.4 h for released docetaxel.

Conclusion: CPC634 could be administered safely upon pretreatment with dexamethasone. Cumulative skin toxicity was the main DLT. The recommended phase 2 dose was determined at 60 mg/m Q3W with dexamethasone premedication.