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).

BACKGROUND

TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional doxorubicin liposomal formulations in preclinical models. This phase I first-in-human study aimed to define the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary activity of TLD-1 in patients with advanced solid tumors.

PATIENTS AND METHODS

We recruited patients with advanced solid tumors who failed standard therapy and received up to 3 prior lines of palliative systemic chemotherapy. TLD-1 was administered intravenously every 3 weeks up to a maximum of 9 cycles (6 for patients with prior anthracyclines) from a starting dose of 10 mg/m

RESULTS

30 patients were enrolled between November 2018 and May 2021. No dose-limiting toxicities (DLT) were observed. Maximum administered dose of TLD-1 was 45 mg/m

CONCLUSIONS

The new liposomal doxorubicin formulation TLD-1 showed a favourable safety profile and antitumor activity, particularly in breast cancer. RP2D was defined at 40 mg/m

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Ilaria Colombo: Travel grants: Tesaro, Janssen, AZ, GSK. Honoraria for consultancy or expert opinion: AZ, GSK, Novartis, MSD, BionTech. Institutional grants for clinical trials (PI): MSD, Bayer, Vivesto, Incyte, AZ, Orion. Kira-Lee Koster: Travel grants for congress visits from Takeda Pharma AG und Janssen-Cilag AG (paid to institution). Lisa Holer: no conflict of interest. Simon Haefliger: no conflict of interest. Manuela Rabaglio: no conflict of interest. Sara Bastian: no conflict of interest. Michael Schwitter: no conflict of interest. Katrin Eckhardt: no conflict of interest. Stefanie Hayoz: no conflict of interest. Anna M. Mc Laughlin: current employee of Pharmetheus AB and a paid consultant to multiple pharmaceutical companies. Charlotte Kloft: no conflict of interest. Marian Klose: no conflict of interest. Stefan Halbherr: Stefan Halbherr owns shares of InnoMedica Holding AG and functions as part of the executive management of the firm. Christian Baumgartner: Christian Baumgartner hold shares of Innomedica and is a former employee of the firm. He has received advisory fees from Boehringer Ingelheim. Cristiana Sessa: no conflict of interest. Anastasios Stathis: Institutional funding for clinical trials: Innomedica, Abbvie; ADC Therapeutics; Amgen, Astra Zeneca; Bayer; Cellestia; Incyte, Loxo Oncology; Merck MSD; Novartis; Pfizer; Philogen; Roche. Consultant/expert testimony/advisory board (institutional): Debiopharm, Janssen, AstraZeneca, Incyte, Eli Lilly, Novartis, Roche, Loxo Oncology. Travel grant: Incyte; Astra Zeneca. Dagmar Hess: no conflict of interest. Markus Joerger: Advisory role (institutional): Novartis, Astra Zeneca, Basilea Pharmaceutica, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi; research funding: Swiss Cancer Research; travel grants: Roche, Sanofi, Takeda.