Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma - 24/04/13
, Michael Girardi, MD b, Madeleine Duvic, MD c, Timothy Kuzel, MD d, Brian K. Link, MD e, Lauren Pinter-Brown, MD f, Alain H. Rook, MD g
Reprint requests: Youn H. Kim, MD, Multidisciplinary Cutaneous Lymphoma Program, Stanford Cancer Center, 875 Blake Wilbur Dr, Stanford, CA 94305.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.
Le texte complet de cet article est disponible en PDF.Key words : cancer immunotherapy, CPG oligodeoxynucleotides, cutaneous T-cell lymphoma, immunotherapy, PF-3512676, Toll-like receptor 9
Abbreviations used : AE, CAILS, CR, CTCL, DC, DLT, IL, MF, MTD, ODN, pDC, PR, SS, TH, TLR
Plan
| Support for this study and for editorial assistance was provided by Pfizer Inc. |
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| Disclosure: Dr Rook received honoraria as a consultant for Merck and Hy BioPharma and as a speaker for Therakos. Dr Duvic received grant funding from Pfizer as an investigator. Dr Kuzel received honoraria as a speaker for Pfizer. Drs Girardi and Link received grant funding from Coley as investigators. Drs Kim and Pinter-Brown have no conflicts of interest to declare. |
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| Clinical Trials Registration Number: NCT00091208. |
Vol 63 - N° 6
P. 975-983 - décembre 2010 Retour au numéro
Article précédent
- Change of Address
- A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis
- Alain H. Rook, Gary S. Wood, Madeleine Duvic, Eric C. Vonderheid, Alfonso Tobia, Bernard Cabana
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