TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: Dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65/16)

• DOI: 10.1016/j.ejca.2024.113588
• Publication Date: 2024-02-02T17:25:42Z
• Authors: Ilaria Colombo; Kira-Lee Koster; Lisa Holer; Simon Haefliger; Manuela Rabaglio; Sara Bastian; Michael Schwitter; Katrin Eckhardt; Stefanie Hayoz; Anna M. Mc Laughlin; Charlotte Kloft; Marian Klose; Stefan Halbherr; Christian Baumgar...; Cristiana Sessa; Anastasios Stathis; Dagmar Hess; Markus Joerger
• Keywords: Mucositis

Background TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional formulations in preclinical models. This phase I first-in-human study aimed define the maximum tolerated dose (MTD), recommended 2 (RP2D), safety and preliminary activity of patients with advanced solid tumors. Patients methods We recruited tumors who failed standard therapy received up 3 prior lines palliative systemic chemotherapy. was administered intravenously every weeks 9 cycles (6 for anthracyclines) from starting 10 mg/m2, according an accelerated titration design followed by modified continual reassessment method. Results 30 were enrolled between November 2018 May 2021. No dose-limiting toxicities (DLT) observed. Maximum 45 RP2D defined at 40 mg/m2. Most frequent treatment-related adverse events (TRAE) any grade included palmar-plantar erythrodysesthesia (PPE) (50% patients), oral mucositis (50%), fatigue (30%) skin rash (26.7%). common G3 TRAE PPE 4 (13.3%) (6.7%). Overall objective response rate 10% whole population 23.1% among 13 breast cancer; median time-to-treatment failure 2.7 months. exhibit linear pharmacokinetics, terminal half-life 95 hours. Conclusions The new formulation showed favourable profile antitumor activity, particularly cancer. mg/m2 weeks. (NCT03387917)