Sureda, AnnaPinto, AntonioGhesquières, HervéMorschhauser, FranckTournilhac, OlivierMutsaers, PimZijlstra, Josée M.De Filippi, RosariaHilgier, KasiaManamley, NickJanik, TomasZinzani, Pier Luigi2025-04-012025-04-012025-01-010278-0232https://hdl.handle.net/2445/220168A significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first-line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open-label, two-stage trial investigating the safety and efficacy of tinostamustine in patients ≥ 18 years with relapsed/refractory (R/R) hematological malignancies, including HL. Stage 1 involved dose-escalation to determine the maximum tolerated dose (MTD) of tinostamustine, optimal infusion time and recommended Phase II dose (RP2D). Stage 2 confirmed the safety and efficacy of the RP2D in expansion cohorts of selected R/R hematological malignancies. Ten patients with heavily pre-treated HL entered dose-escalation, with nine patients experiencing treatment-emergent adverse events (TEAEs) considered to be related to study treatment-primarily hematological toxicities. MTD was 100 mg/m2 tinostamustine over 60 min and signals of efficacy were observed for patients with HL. In Stage 2, all 20 patients with HL experienced ≥ 1 TEAE, which were principally hematological or gastrointestinal. There were no tinostamustine-related deaths in either stage of the study. Overall response rate in Stage 2 was 37% (2 complete responses, 5 partial responses; 95% confidence interval [CI]: 16%, 62%) and median progression-free survival 3.8 months (95% CI: 2.2-9.4 months). Tinostamustine is a promising new therapeutic approach for the treatment of patients with R/R classical HL with limited options. This study demonstrates a predictable and manageable safety profile with signals of efficacy.11 p.application/pdfengcc by-nc-nd (c) Sureda, Anna et al., 2025https://creativecommons.org/licenses/by-nc-nd/4.0/Medicaments antineoplàsticsResistència als medicamentsMalaltia de HodgkinAntineoplastic agentsDrug resistanceHodgkin's diseaseinfo:eu-repo/semantics/article7578272025-04-01info:eu-repo/semantics/openAccess39617826