Phase i trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma

Youn H. Kim; Michael Girardi; Madeleine Duvic; Timothy Kuzel; Brian K. Link; Lauren Pinter-Brown; Alain H. Rook

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

Youn H. Kim, Michael Girardi, Madeleine Duvic, Timothy Kuzel, Brian K. Link, Lauren Pinter-Brown, Alain H. Rook

Dermatology

Research output: Contribution to journal › Article › peer-review

89 Scopus citations

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.

Original language	English (US)
Pages (from-to)	975-983
Number of pages	9
Journal	Journal of the American Academy of Dermatology
Volume	63
Issue number	6
DOIs	https://doi.org/10.1016/j.jaad.2009.12.052
State	Published - Dec 2010

Funding

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.

Keywords

CPG oligodeoxynucleotides
Cancer immunotherapy
Cutaneous T-cell lymphoma
Immunotherapy
PF-3512676
Toll-like receptor 9

ASJC Scopus subject areas

Dermatology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaad.2009.12.052

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@article{571344b1a9f647b8aae41fe5b996c2ce,

title = "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 S{\'e}zary 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 S{\'e}zary 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.",

keywords = "CPG oligodeoxynucleotides, Cancer immunotherapy, Cutaneous T-cell lymphoma, Immunotherapy, PF-3512676, Toll-like receptor 9",

author = "Kim, {Youn H.} and Michael Girardi and Madeleine Duvic and Timothy Kuzel and Link, {Brian K.} and Lauren Pinter-Brown and Rook, {Alain H.}",

note = "Funding Information: 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. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.",

year = "2010",

month = dec,

doi = "10.1016/j.jaad.2009.12.052",

language = "English (US)",

volume = "63",

pages = "975--983",

journal = "Journal of the American Academy of Dermatology",

issn = "0190-9622",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - Phase i trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma

AU - Kim, Youn H.

AU - Girardi, Michael

AU - Duvic, Madeleine

AU - Kuzel, Timothy

AU - Link, Brian K.

AU - Pinter-Brown, Lauren

AU - Rook, Alain H.

N1 - Funding Information: 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. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.

PY - 2010/12

Y1 - 2010/12

N2 - 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.

AB - 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.

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KW - Cancer immunotherapy

KW - Cutaneous T-cell lymphoma

KW - Immunotherapy

KW - PF-3512676

KW - Toll-like receptor 9

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JO - Journal of the American Academy of Dermatology

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Phase i trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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