期刊
CLINICAL CANCER RESEARCH
卷 28, 期 23, 页码 5079-5087出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-21-4486
关键词
-
类别
资金
- Jacquelyn A. Brady Fund
- NIH [RP1100584]
- Cancer Prevention and Research Institute of Texas [1U01 CA180964]
- Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy [t UL1 TR000371]
- NCATS [P30 CA016672]
- MD Anderson Cancer Center Support Grant [P30CA016056]
- Roswell Comprehensive Cancer Center
- NCI [1R50CA211108]
- Idera Pharmaceuticals
- [R01CA242845]
This study investigated the safety, dose, efficacy, and immune effects of the investigational synthetic Toll-like receptor 9 (TLR9) agonist Tilsotolimod in multiple solid tumors. The results showed that Tilsotolimod monotherapy was generally well tolerated and induced rapid, significant alterations in the tumor microenvironment.
Purpose: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratu-moral (it) tilsotolimod monotherapy in multiple solid tumors.Patients and Methods: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the safety, establishing the dose, efficacy, and immunologic assessment. Blood samples and tumor biopsies of injected and noninjected lesions were obtained at baseline and 24 hours after treatment for immune analyses.Results: Thirty-eight and 16 patients were enrolled into the dose escalation and melanoma expansion cohorts, respectively. Deep visceral injections were conducted in 91% of patients. No dose-limiting toxicities (DLT) or grade 4 treatment-related adverse events were observed. Biopsies 24 hours after treatment demonstrated an increased IFN pathway signature and dendritic cell maturation. Immunologic profiling revealed upregulation of IFN-signaling genes and modulation of genes for checkpoint proteins. In the dose escalation cohort, 12 (34%) of 35 evaluable patients achieved a best overall response rate (ORR) of stable disease (SD), whereas 3 (19%) of 16 evaluable patients in the melanoma cohort achieved stable disease.Conclusions: Overall, tilsotolimod monotherapy was generally well tolerated and induced rapid, robust alterations in the tumor microenvironment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据