Safety and preliminary efficacy results of a new micellar formulation of docetaxel in patients with metastatic castration-resistant prostate cancer - SAKK 67/20 trial.

Docetaxel micellar (DM) is a novel polysorbate-free docetaxel formulation that does not require steroid premedication. The aim of this study was to define the safety, pharmacokinetics (PK) and preliminary activity of DM in patients with metastatic castration-resistant prostate cancer (mCRPC). DM was administered intravenously to chemotherapy-naïve patients with mCRPC every 3 weeks following a 3 + 3 design (75, 90, 100 mg/m2) until disease progression or unacceptable toxicity (maximum 10 cycles). A total of 11 patients were recruited from June 2021 to April 2023. No dose limiting toxicities (DLT) were observed at 75 or 90 mg/m2. Two out of 5 patients experienced DLT at 100 mg/m2 (grade 4 neutropenia ≥ 7 days and grade 2 nausea/fatigue/diarrhoea requiring dose reduction at cycle 2, respectively). Most frequent all-grades TRAE included fatigue (91%), neutropenia (82%), alopecia (64%), diarrhoea (55%), peripheral edema (45%) and peripheral sensory neuropathy (45%). Infusion-related reactions or febrile neutropenia were not observed. Four out of 11 (36%) patients achieved a PSA50 response, 4/9 (44%) evaluable patients achieved a radiological response. DM exhibited linear PK with tri-phasic elimination (clearance 26.6 L/h, 20% inter-individual PK variability). While 3-weekly intravenous DM at 90 mg/m2 was not associated with DLT, no formal dosing recommendation was made for premature closure of the 100 mg/m2 cohort. Steroid-free 3-weekly DM at a dose of 90 mg/m2 was not associated with DLT. Preliminary activity of DM appeared consistent with historical outcomes reported for conventional docetaxel in patients with mCRPC (NCT04629781).