Phase I dose-escalation study of an oral administration of the pan-histonedeacetylase inhibitor abexinostat combined with a fixed dose of doxorubicin in patients with solid tumors.

2575 Background: Preclinical data indicate that abexinostat enhances sensitivity to DNA-damaging agents, such as doxorubicin, particularly when administered 48h before infusion. A phase I dose-escalation study of abexinostat in combination with doxorubicin was performed in candidate patients to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT), and establish the recommended phase II dose (RP2D). Methods: Abexinostat was given 4 consecutive days weekly, 3 out of 4 weeks, and fixed doxorubicin dose of 25 mg/m2 was administered on day 3 of each weekly abexinostat schedule, for a maximum of 6 cycles. Results: 35 patients were included and treated: 23 in the dose-escalation phase in cohorts receiving abexinostat 30 to 75 mg/m² bid, and 12 in the confirmation phase at the RP2D. In the dose-escalation phase, MTD was 75 mg/m² bid with 3 DLTs 2 grade 4 thrombocytopenia, 1 grade 2 neutropenia >7 days. In the confirmation phase (RP2D 60 mg/m² bid), there were 4 DLTs (33% patients): 2 grad...