Oasmia Pharmaceutical (Sweden)

3526 Background: Docetaxel micellar (DM) is a nano-sized particle formulation of docetaxel in which a retinoic acid derivative is used as solubilizer with a high drug to excipient ratio possibly resulting in reduced systemic toxicity or hypersensitivity reactions due to the excipient. DM is given without standard use of premedication, avoiding steroid-associated immunosuppression. Here we present the pharmacokinetics (PK) after a single dose of DM or polysorbate-solubilized docetaxel (D) as well as safety and early activity including overall response rate (ORR) in female patients with metastatic breast cancer. Methods: The PK study was a two-cycle, cross-over study where 30 patients were included and randomized to either DM followed by D or D followed by DM, both given as a 1-hour intravenous infusion at a dose of 100mg/m2. The phase II study was a prospective, multicenter, open-label, third-party blinded, randomized, parallel group, active-controlled study including 200 patients to compare the early activity and safety of DM and D, both given as 100 mg/m2 1-hour intravenous infusion every 21 days (1 cycle) for a total of 6 cycles. Results: Bioequivalence of total docetaxel in plasma, AUC0-last and Cmax, was demonstrated for DM compared to D. The incidence of adverse events was higher in the D arm than in the DM arm for the majority of SOCs and PTs in the phase II study. Overall, Grade 3 or 4 AEs were reported for 82.7% of patients from DM arm and 99.0% of patients from D arm. Twelve (12.2%) patients in the DM arm and 24 (24.0%) patients in the D arm needed at least one dose reduction due to AEs. The primary efficacy endpoint in the phase II study was based on the assessment according to Response Evaluation Criteria in Soldid Tumors (RECIST) 1.1 and non-inferiority was not reached based on the pre-defined non-inferiority margin. A post-hoc analysis investigating the ORR based on tumour assessment at the end of chemotherapy, and non-inferiority of DM as compared to D was shown (ITT population). Conclusions: DM is bioequivalent to D regarding total drug in plasma and provides a docetaxel formulation that spares patients steroid premedication. An improved safety profile for DM compared to D was shown while additional efficacy data is needed for future development of DM. Eudra CT: 2012-005161-12 and 2013-004889-33. Clinical trial information: 2012-005161-12 and 2013-004889-33 .