期刊
CANCER DISCOVERY
卷 8, 期 10, 页码 1250-1257出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-18-0280
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资金
- Dynavax Technologies Corporation
- Parker Institute for Cancer Immunotherapy
- NIH [R35 CA197633]
PD-1 inhibitors are approved for treating advanced melanoma, but resistance has been observed. This phase lb trial evaluated intratumoral SD-101, a synthetic CpG oligonucleotide that stimulates Toll-like receptor 9 (TLR9), in combination with pembrolizumab in patients with unresectable or metastatic malignant melanoma. The most common adverse events related to SD-101 were injection-site reactions and transient, mild-to-moderate flu-like symptoms. Among the 9 patients naive to anti-PD-1 therapy, the overall response rate (ORR) was 78%. The estimated 12-month progression-free survival rate was 88%, and the overall survival rate was 89%. Among 13 patients having prior anti-PD-1 therapy, the ORR was 15%. RNA profiling of tumor biopsies demonstrated increased CD8(+) T cells, natural killer cells, cytotoxic cells, dendritic cells, and B cells. The combination of intratumoral SD-101 and pembrolizumab was well tolerated and induced broad immune activation in the tumor microenvironment with durable tumor responses in both peripheral and visceral lesions. SIGNIFICANCE: These early data demonstrate that the combination of pembrolizumab with intratumoral SD-101 is well tolerated and can induce immune activation at the tumor site. Combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade can potentially increase clinical efficacy with minimal additional toxicity relative to PD-1 blockade alone. (C) 2018 AACR.
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