1957P - Results from a phase I/II trial of tinostamustine monotherapy in advanced solid tumours (NCT03345485): Safety and efficacy in a subset of patients (pts) with soft tissue sarcoma (STS)

Background

Tinostamustine, a novel alkylating deacetylase inhibitor, improves drug access to cancer cell DNA strands, breaks them and counteracts damage repair. Here we report safety and efficacy of tinostamustine in a subset of pts with STS from an open-label Ph I/II trial.

Methods

Pts ≥18 years with advanced solid tumours, life expectancy >3 mo, Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 were enrolled. Ph I dose escalation (standard 3+3 design 60–100mg/m²) defined the maximum tolerated dose and recommended Ph II dose (RP2D). In Ph II, the objective response rate (complete response + partial response [PR]), together with pts with stable disease (SD) ≥4 mo duration, following the RP2D (80mg/m² over 60 min on D1 & 15 of each 4-wk treatment cycle) were determined, and are summarised here using descriptive statistics. Two substudies characterised the effects of tinostamustine (60–80mg/m²) on cardiac repolarisation.

Results

Forty-nine pts with advanced solid tumours (13 with STS) were enrolled (Table). In Ph II, tinostamustine-related treatment-emergent adverse events (TEAEs) included thrombocytopenia, anaemia, nausea and fatigue. Serious tinostamustine-related AEs were mainly haematological; 1 tinostamustine-related fatal AE (intra-abdominal haemorrhage; ovarian cancer pt) occurred. In the STS subset, a greater proportion of patients experienced tinostamustine-related and serious tinostamustine-related TEAEs compared with the overall Ph II pt population; there were no tinostamustine-related fatal TEAEs. One pt with STS achieved PR as best response, and 3 had SD ≥4 mo duration; 5 pts with STS discontinued treatment due to progressive disease.

Table: 1957P

Demographic & safety data: Pts with advanced solid tumours receiving tinostamustine & the STS pt subset

*Ph I, II & substudies safety analysis set. ^†Ph II & substudies safety analysis set. AE, adverse event; ECOG-PS, Eastern Cooperative Oncology Group performance status; Ph, Phase; STS, soft tissue sarcoma; TEAE, treatment-emergent adverse event

Conclusions

Tinostamustine demonstrated modest signals of efficacy with manageable tolerability in pts with STS.

Clinical trial identification

NCT03345485.

Editorial acknowledgement

Editorial support (in the form of writing assistance, collating author comments, assembling tables/figures, grammatical editing and referencing) was provided by Sarah Birch, PhD at Makara Health Communications Ltd, and was funded by Mundipharma Research Ltd and Purdue Pharma, LP.

Legal entity responsible for the study

Mundipharma Research Ltd.

Funding

Mundipharma Research Ltd and Purdue Pharma LP.

Disclosure

R. Chugh: Financial Interests, Personal and Institutional, Research Funding: Mundipharma, Ayala, Cogent, PTC Therapeutics, Cornerstone, Trillium, GSK, Springworks Therapeutics, Astex Pharmaceuticals; Financial Interests, Personal, Advisory Role: Jazz Pharmaceuticals, Springworks Therapeutics. S. Kummar: Financial Interests, Personal, Advisory Board: Bayer, Gilead, Mundibiopharma, Boehringer Ingelheim, Springworks Theraepeutics, HarbourBiomed, Boehringer Ingelheim, Oxford BioTherapeutics; Financial Interests, Personal, Advisory Board, Spouse: Cadila Pharmaceuticals; Financial Interests, Personal, Other, Chair, DSMC: Mirati; Financial Interests, Personal, Advisory Board, Consultant: Genome Insight; Financial Interests, Personal, Ownership Interest: Pahtomiq; Financial Interests, Personal, Ownership Interest, Spouse (co-founder): Arexeon; Financial Interests, Personal, Other, co-founder: Pathomiq; Financial Interests, Institutional, Invited Speaker: ADC Therapeutics, Pionyr Therapeutics, Eisai, BMS, Syndax, SeaGen, ORIC, EMD Serono, Genome & Company, Moderna, Amgen, ASTX Therapeutics, PMV Pharmaceuticals, Elevation Oncology, VelosBio Inc, Gilead, Day One Biopharmaceuticals, Vincerx Pharma, Inc; Financial Interests, Institutional, Invited Speaker, trial funding: 23&Me. T. Janik, K. Hilgier: Financial Interests, Personal, Full or part-time Employment: Mundipharma Research Ltd. N. Manamley: Financial Interests, Institutional, Full or part-time Employment: Mundipharma. J. Strauss: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Member of Board of Directors: Dialectic Therapeutics; Financial Interests, Personal, Full or part-time Employment: Dialectic Therapeutics; Financial Interests, Personal, Stocks/Shares: AbbVie, Abbott Laboratories, BMS, Intuitive Surgical, Johnson & Johnson, Merck, Regeneron; Financial Interests, Personal, Other, Data Safety Monitoring Board: BerGenBio ASA. All other authors have declared no conflicts of interest.