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#163 Results from a phase I/II trial of tinostamustine monotherapy in advanced solid tumours (NCT03345485): safety and efficacy in a subset of patients with advanced ovarian cancer (OvCa)
  1. Anna V Tinker1,
  2. Rashmi Chugh2,
  3. Giuseppe Curigliano3,
  4. Shivaani Kummar4,
  5. Reva Schneider5,
  6. James Strauss5,
  7. Tomas Janik6,
  8. Nick Manamley6,
  9. Kasia Hilgier6 and
  10. Ana Oaknin7
  1. 1BC Cancer, Vancouver, Canada
  2. 2University of Michigan Rogel Comprehensive Cancer Center, Ann Arbor, USA
  3. 3European Institute of Oncology, IRCCS, Milan, Italy
  4. 4Oregon Health and Science University, Portland, USA
  5. 5Mary Crowley Cancer Research, Dallas, USA
  6. 6Mundipharma Research Ltd, Cambridge, UK
  7. 7Gynaecologic Cancer Programme; Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain


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.

Abstract #163 Table 1

Demographic and safety data for the entire Phase II population of patients with advanced solid tumours receiving tinostamustine and the OvCa patient subset

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

Funding Mundipharma Research Limited and Purdue Pharma LP.

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