A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma

BMC Cancer

John Whittaker¹  Lai Mun Wang²  Gabrielle Rees²  Daniel Royston²  Catherine Hildyard³  Stephen W. Booth⁴  Murali Kesavan⁴  Graham P. Collins⁴  Toby A. Eyre⁴  Leticia Campo⁵  Farasat Kazmi⁵  Mark R. Middleton⁵  David Kerr⁶  Nick La Thangue⁶  Elizabeth Soilleux⁷ 

[1] Celleron Therapeutics Ltd, Oxford, UK;Department of Cellular Pathology, Oxford University Hospitals, Oxford, UK;Department of Haematology, Milton Keynes University Hospital, Milton Keynes, UK;Department of Haematology, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, Oxford, UK;Department of Oncology, University of Oxford, Oxford, UK;Department of Oncology, University of Oxford, Oxford, UK;Celleron Therapeutics Ltd, Oxford, UK;Department of Pathology, University of Cambridge, Cambridge, UK;

关键词: Histone deacetylase (HDAC);    HR23B;    Biomarker;    Lymphoma;   

DOI  :  10.1186/s12885-021-08595-w

来源: Springer

【 摘 要 】

BackgroundThis Phase 2a dose expansion study was performed to assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose of the oral histone de-acetylase (HDAC) inhibitor CXD101 in patients with relapsed / refractory lymphoma or advanced solid organ cancers and to assess HR23B protein expression by immunohistochemistry as a biomarker of HDAC inhibitor sensitivity.MethodsPatients with advanced solid-organ cancers with high HR23B expression or lymphomas received CXD101 at the recommended phase 2 dose (RP2D). Key exclusions: corrected QT > 450 ms, neutrophils < 1.5 × 109/L, platelets < 75 × 109/L, ECOG > 1. Baseline HR23B expression was assessed by immunohistochemistry.ResultsFifty-one patients enrolled between March 2014 and September 2019, 47 received CXD101 (19 solid-organ cancer, 28 lymphoma). Thirty-four patients received ≥80% RP2D. Baseline characteristics: median age 57.4 years, median prior lines 3, male sex 57%. The most common grade 3–4 adverse events were neutropenia (32%), thrombocytopenia (17%), anaemia (13%), and fatigue (9%) with no deaths on CXD101. No responses were seen in solid-organ cancers, with disease stabilisation in 36% or patients; the overall response rate in lymphoma was 17% with disease stabilisation in 52% of patients. Median progression-free survival was 1.2 months (95% confidence interval (CI) 1.2–5.4) in solid-organ cancers and 2.6 months (95%CI 1.2–5.6) in lymphomas. HR23B status did not predict response.ConclusionsCXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted.Trial registrationClinicalTrials.gov identifier NCT01977638. Registered 07 November 2013.

【 授权许可】

CC BY