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 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.
  
  
  CONCLUSIONS
  This trial was not designed to rigorously assess efficacy.
  
  
  CONCLUSIONS
  Single-agent PF-3512676 was well tolerated and demonstrated antitumor activity in patients with refractory CTCL.
authors.affiliation: Department of Dermatology, Multidisciplinary Cutaneous Lymphoma Program, Stanford Cancer Center, Stanford, California 94305, USA. younkim@stanford.edu
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.forename: Michael
authors.initials: M
authors.lastname: Girardi
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Timothy
authors.initials: T
authors.lastname: Kuzel
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Lauren
authors.initials: L
authors.lastname: Pinter-Brown
authors.forename: Alain H
authors.initials: AH
authors.lastname: Rook
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000009:adverse effects*; D012878:Skin Neoplasms / Q000188:drug therapy*; D051217:Toll-Like Receptor 9 / Q000819:agonists*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D009838:Oligodeoxyribonucleotides; C483020:ProMune; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9