Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma
- PMID: 20888065
- DOI: 10.1016/j.jaad.2009.12.052
Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma
Abstract
Background: Mycosis fungoides and Sézary syndrome are a class of lymphomas of skin-trafficking T cells, and they are the most common forms of cutaneous T-cell lymphoma (CTCL). Mycosis fungoides and Sézary syndrome are chronic, frequently incurable diseases with limited therapeutic options. PF-3512676 (formerly CPG 7909) is a Toll-like receptor 9 agonist that is being investigated for treatment of patients with advanced cancer.
Objective: This study was conducted to determine the safety and tolerability of single-agent PF-3512676 in patients with CTCL.
Methods: In this phase I dose-escalation study, patients (N = 28) with treatment-refractory, stage IB to IVA CTCL were enrolled in 6 sequential cohorts and treated with PF-3512676 (0.08, 0.16, 0.24, 0.28, 0.32, or 0.36 mg/kg) administered as 24 weekly subcutaneous injections. Primary end points were safety and tolerability.
Results: Common adverse events (fatigue, rigors, injection-site reactions, myalgia, lymphopenia, leukopenia, neutropenia, and pyrexia) were mostly grade 1 or 2, and no patient developed specific symptoms associated with autoimmune disease. Clinical response rate to PF-3512676, as determined by both Composite Assessment of Index Lesion Severity and Physician Global Assessment, was 32% (3 complete clinical responses, 6 partial responses); the majority of responses (7/9; 78%) were ongoing at the end of study.
Limitations: This trial was not designed to rigorously assess efficacy.
Conclusion: Single-agent PF-3512676 was well tolerated and demonstrated antitumor activity in patients with refractory CTCL.
Trial registration: ClinicalTrials.gov NCT00091208.
Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Similar articles
-
Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma.J Clin Oncol. 2007 Jul 20;25(21):3109-15. doi: 10.1200/JCO.2006.10.2434. Epub 2007 Jun 18. J Clin Oncol. 2007. PMID: 17577020 Clinical Trial.
-
FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma.Oncologist. 2007 Oct;12(10):1247-52. doi: 10.1634/theoncologist.12-10-1247. Oncologist. 2007. PMID: 17962618 Clinical Trial.
-
Comparison of selective retinoic acid receptor- and retinoic X receptor-mediated efficacy, tolerance, and survival in cutaneous t-cell lymphoma.J Am Acad Dermatol. 2004 Jul;51(1):25-32. doi: 10.1016/j.jaad.2003.11.058. J Am Acad Dermatol. 2004. PMID: 15243520 Clinical Trial.
-
Cutaneous T-cell lymphoma.Semin Oncol Nurs. 2006 May;22(2):90-6. doi: 10.1016/j.soncn.2006.01.005. Semin Oncol Nurs. 2006. PMID: 16720231 Review.
-
Cutaneous T cell lymphoma: the helping hand of dendritic cells.Ann N Y Acad Sci. 2001 Sep;941:1-11. Ann N Y Acad Sci. 2001. PMID: 11594563 Review.
Cited by
-
Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives.Front Immunol. 2023 Sep 26;14:1244345. doi: 10.3389/fimmu.2023.1244345. eCollection 2023. Front Immunol. 2023. PMID: 37822929 Free PMC article. Review.
-
Harnessing the immune system in the treatment of cutaneous T cell lymphomas.Front Oncol. 2023 Jan 12;12:1071171. doi: 10.3389/fonc.2022.1071171. eCollection 2022. Front Oncol. 2023. PMID: 36713518 Free PMC article.
-
Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.Bioimpacts. 2022;12(3):261-290. doi: 10.34172/bi.2022.23896. Epub 2022 Mar 26. Bioimpacts. 2022. PMID: 35677663 Free PMC article. Review.
-
CpG Oligodeoxynucleotides for Anticancer Monotherapy from Preclinical Stages to Clinical Trials.Pharmaceutics. 2021 Dec 28;14(1):73. doi: 10.3390/pharmaceutics14010073. Pharmaceutics. 2021. PMID: 35056969 Free PMC article. Review.
-
Modified internucleoside linkages for nuclease-resistant oligonucleotides.RSC Chem Biol. 2020 Dec 8;2(1):94-150. doi: 10.1039/d0cb00136h. eCollection 2021 Feb 1. RSC Chem Biol. 2020. PMID: 34458777 Free PMC article. Review.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical