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01-12-2021 | Lymphoma | Research article

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

Authors: Stephen W. Booth, Toby A. Eyre, John Whittaker, Leticia Campo, Lai Mun Wang, Elizabeth Soilleux, Daniel Royston, Gabrielle Rees, Murali Kesavan, Catherine Hildyard, Farasat Kazmi, Nick La Thangue, David Kerr, Mark R. Middleton, Graham P. Collins

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

This 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.

Methods

Patients 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.

Results

Fifty-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.

Conclusions

CXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted.

Trial registration

ClinicalTrials.gov identifier NCT01977638. Registered 07 November 2013.

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Title: 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
Authors: Stephen W. Booth
Toby A. Eyre
John Whittaker
Leticia Campo
Lai Mun Wang
Elizabeth Soilleux
Daniel Royston
Gabrielle Rees
Murali Kesavan
Catherine Hildyard
Farasat Kazmi
Nick La Thangue
David Kerr
Mark R. Middleton
Graham P. Collins
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Lymphoma
Biomarkers
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08595-w

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