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

Booth, SW; Eyre, TA; Whittaker, J; Campo, L; Wang, LM; Soilleux, E; Royston, D; Rees, G; Kesavan, M; Hildyard, C; Kazmi, F; La Thangue, N; Kerr, D; Middleton, MR; Collins, GP

Journal 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

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. 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

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Booth, S. W., Eyre, T. A., Whittaker, J., Campo, L., Wang, L. M., Soilleux, E., Royston, D., Rees, G., Kesavan, M., Hildyard, C., Kazmi, F., La Thangue, N., Kerr, D., Middleton, M. R., & Collins, G. P. (2021). 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, 21(1), 851–851.

MLA Style

Booth, SW, et al. “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, vol. 21, no. 1, 2021, pp. 851–51.

Chicago Style

Booth, SW, TA Eyre, J Whittaker, et al. 2021. “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 21 (1): 851–51.
Print