Abstract 575P
Background
TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional liposomal formulations of doxorubicin in preclinical in vivo models. This phase I first-in-human trial is aiming to determine the recommended phase II dose (RP2D), toxicity profile, pharmacokinetics and preliminary activity.
Methods
Patients (pts) treated with a maximum of 3 prior lines of systemic chemotherapy are eligible. TLD-1 was administered on day 1 iv over 60-90 minutes (depending on individual dose) q 21 days, for up to 6 or 9 cycles (depending on prior exposure to anthracyclines) with premedication of 8mg dexamethasone. Dose level (DL) escalation was performed as follows: DL1=10mg/m2, DL2=16mg/m2, DL3=23mg/m2, DL4=30mg/m2, DL5=35mg/m2, DL6=40mg/m2 and DL7=45mg/m2, with an accelerated titration design (ATD), treating one pt at each DL up to DL6, followed by a modified continual reassessment method in DL7.
Results
12 pts have been treated, one each at DLs 1-6 and 6 pts at DL7. 3 pts had breast and 3 ovarian cancer. Other tumortypes were one cholangio-, colon-, adnexal-, pancreatic-, uterine-carcinoma and mesothelioma each. Median age was 67 years (39-83), 5 pts had prior anthracyclines. 11 pts received a median of 4 cycles (2-6), 1 pt is still on treatment. No dose limiting toxicities occurred during cycle 1. At DL4 the pt experienced mucositis G2 in C3 and PPE G2 in C4 resulting in delay of subsequent cycles. At DL5 the pt had a G2 mucositis in C2 and went off due to PD. The pt at DL6 experienced rash G2 and PPE G3 in C3 leading to dose reduction and treatment delay. At DL7 1 pt had rash G2, 1 pt PPE G2 and 1 pt PPE G3 out of 6 pts; all events occurred in C3 and lead to a dose reduction and delay of C4. Skin-and mucosa toxicity was categorized as related to TLD-1. Other clinically relevant AEs were not observed. Among 12 pts evaluable for response, 1 breast cancer pt had a partial response at DL7 and 6 pts had stable disease.
Conclusions
TLD-1 can be safely administered up to a dose of 45mg/m2, however, G2/3 cumulative PPE was observed in 4/12 pts. The trial is currently beeing expanded to gain more information on cumulative toxicities and to better define the RP2D.
Clinical trial identification
NCT03387917.
Editorial acknowledgement
Legal entity responsible for the study
Swiss Group for Clinical Cancer Research (SAKK).
Funding
Swiss Group for Clinical Cancer research.
Disclosure
D. Hess: Shareholder/Stockholder/Stock options, all outside the submitted work: Pharmaceutical companies. S. Haefliger: Advisory/Consultancy: AstraZenca; Advisory/Consultancy: Bayer. C. Kloft: Research grant/Funding (institution), all outside the submitted work: industry consortium. A. Stathis: Research grant/Funding (institution), all outside the submitted work: Pharmaceutical Companies. All other authors have declared no conflicts of interest.