TLD-1, a Novel Liposomal Doxorubicin, in Patients with Solid Tumors: Comparative Pharmacokinetics and Final Results of a Multicenter Phase 1 Study (SAKK 65/16)
Targeted liposomal doxorubicin (TLD-1) is a novel PEGylated liposomal doxorubicin (PLD) with optimized formulation characteristics, developed to improve the benefit-risk profile of PLD. This randomized intrapatient crossover amendment to the phase 1 SAKK 65/16 trial (NCT03387917) compared the pharmacokinetics (PK) of TLD-1 and Caelyx™ and included a pooled analysis of safety and preliminary antitumor activity at the recommended phase 2 dose (RP2D). Patients with advanced breast or platinum-resistant ovarian cancer in the comparative PK part were randomized to receive TLD-1 in cycle 1 and Caelyx™ in cycle 2, or vice versa, followed by TLD-1 thereafter. Both formulations were administered intravenously at 40 mg/m In 10 evaluable patients from the comparative PK part, TLD-1 showed higher encapsulated doxorubicin exposure (AUC Targeted liposomal doxorubicin demonstrated prolonged systemic circulation and low variability in liposomal drug release, likely due to its formulation characteristics. At 40 mg/m NCT03387917, registered 2017-11-21.