CPG 7909（PF-3512676）治疗难治性皮肤 T 细胞淋巴瘤患者的 I 期临床试验

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

机构信息

Department of Dermatology, Multidisciplinary Cutaneous Lymphoma Program, Stanford Cancer Center, Stanford, California 94305, USA.

出版信息

J Am Acad Dermatol. 2010 Dec;63(6):975-83. doi: 10.1016/j.jaad.2009.12.052.

DOI:10.1016/j.jaad.2009.12.052

PMID:20888065

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.

摘要

背景

蕈样真菌病和赛扎里综合征是一类皮肤游走 T 细胞淋巴瘤，是最常见的皮肤 T 细胞淋巴瘤（CTCL）。蕈样真菌病和赛扎里综合征是慢性的、经常无法治愈的疾病，治疗选择有限。PF-3512676（前身为 CPG 7909）是一种 Toll 样受体 9 激动剂，正在研究用于治疗晚期癌症患者。

目的

本研究旨在确定单药 PF-3512676 治疗 CTCL 患者的安全性和耐受性。

方法

在这项 I 期剂量递增研究中，纳入了 28 名治疗抵抗、IB 期至 IVA 期 CTCL 的患者，他们被分为 6 个连续队列，接受 PF-3512676（0.08、0.16、0.24、0.28、0.32 或 0.36mg/kg）治疗，每周皮下注射 24 次。主要终点为安全性和耐受性。

结果

常见不良事件（疲劳、寒战、注射部位反应、肌痛、淋巴细胞减少、白细胞减少、中性粒细胞减少和发热）多为 1 级或 2 级，无患者出现自身免疫疾病相关的特定症状。PF-3512676 的临床反应率，根据综合评估指数病变严重程度和医生整体评估，为 32%（3 例完全临床缓解，6 例部分缓解）；在研究结束时，大多数反应（7/9；78%）仍在持续。