Introduction/Background Tinostamustine, a novel alkylating deacetylase inhibitor, improves drug access to cancer cell DNA strands, breaks them and counteracts damage repair. Here we present the safety and efficacy of tinostamustine in a subset of patients with OvCa enrolled to the Phase I/II clinical trial.

Methodology An open-label trial of tinostamustine in patients ≥18 years with advanced solid tumours, life expectancy >3 months, Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤2. Phase I dose escalation (standard 3+3 design; 60–100mg/m^2) was conducted to define the maximum tolerated dose and recommended Phase II dose (RP2D). In Phase II, objective response rate (complete response [CR] + partial response [PR]), together with the rate of patients with stable disease (SD) ≥4 months’ duration following the RP2D (80mg/m^2 over 60 minutes on Days 1 and 15 of each 4-week treatment cycle) were determined and summarised using descriptive statistics. Two substudies characterised the effects of tinostamustine (60–80mg/m^2) on cardiac repolarisation.

Results Forty-nine patients with advanced solid tumours (18 OvCa) were enrolled (table 1). In the entire population of patients with advanced solid tumours there were no dose-limiting toxicities observed in Phase I. In Phase II, treatment-related adverse events (TEAEs) considered related to tinostamustine were haematological or gastrointestinal. Serious tinostamustine-related AEs were principally haematological. In the subset with OvCa, a greater proportion of patients experienced tinostamustine-related TEAEs and serious tinostamustine-related AEs compared with the overall patient population. One patient with OvCa experienced a fatal AE of intra-abdominal haemorrhage together with Grade 4 haematological AEs, all considered related to tinostamustine. 1/18 patients with OvCa achieved a CR as best response, 1/18 PR, and 7/18 SD ≥4 months’ duration. 10/18 patients discontinued treatment due to progressive disease.

Conclusion Tinostamustine demonstrated signals of efficacy with manageable tolerability in patients with OvCa.

Funding Mundipharma Research Limited and Purdue Pharma LP.