PDF(Pubmed)
Abstract：
UNASSIGNED: The impact of stroma-targeting therapy on tumor immune suppression is largely unexplored. An RNA oligonucleotide, STNM01, has been shown to repress carbohydrate sulfotransferase 15 (CHST15) responsible for tumor proteoglycan synthesis and matrix remodeling. This phase I/IIa study aimed to evaluate the safety and efficacy of STNM01 in patients with unresectable pancreatic ductal adenocarcinoma (PDAC).
UNASSIGNED: This was an open-label, dose-escalation study of STNM01 as second-line therapy in gemcitabine plus nab-paclitaxel-refractory PDAC. A cycle comprised three 2-weekly endoscopic ultrasound-guided locoregional injections of STNM01 at doses of 250, 1,000, 2,500, or 10,000 nM in combination with S-1 (80-120 mg twice a day for 14 days every 3 weeks). The primary outcome was the incidence of dose-liming toxicity (DLT). The secondary outcomes included overall survival (OS), tumor response, changes in tumor microenvironment on immunohistopathology, and safety (jRCT2031190055).
UNASSIGNED: A total of 22 patients were enrolled, and 3 cycles were repeated at maximum; no DLT was observed. The median OS was 7.8 months. The disease control rate was 77.3%; 1 patient showed complete disappearance of visible lesions in the pancreas and tumor-draining lymph nodes. Higher tumoral CHST15 expression was associated with poor CD3+ and CD8+ T cell infiltration at baseline. STNM01 led to a significant reduction in CHST15, and increased tumor-infiltrating CD3+ and CD8+ T cells in combination with S-1 at the end of cycle 1. Higher fold increase in CD3+ T cells correlated with longer OS. There were 8 grade 3 adverse events.
UNASSIGNED: Locoregional injection of STNM01 was well tolerated in patients with unresectable PDAC as combined second-line therapy. It prolonged survival by enhancing T cell infiltration in tumor microenvironment.
UNASSIGNED: The present study was supported by the Japan Agency for Medical Research and Development (AMED).
UNASSIGNED: This was an open-label, dose-escalation study of STNM01 as second-line therapy in gemcitabine plus nab-paclitaxel-refractory PDAC. A cycle comprised three 2-weekly endoscopic ultrasound-guided locoregional injections of STNM01 at doses of 250, 1,000, 2,500, or 10,000 nM in combination with S-1 (80-120 mg twice a day for 14 days every 3 weeks). The primary outcome was the incidence of dose-liming toxicity (DLT). The secondary outcomes included overall survival (OS), tumor response, changes in tumor microenvironment on immunohistopathology, and safety (jRCT2031190055).
UNASSIGNED: A total of 22 patients were enrolled, and 3 cycles were repeated at maximum; no DLT was observed. The median OS was 7.8 months. The disease control rate was 77.3%; 1 patient showed complete disappearance of visible lesions in the pancreas and tumor-draining lymph nodes. Higher tumoral CHST15 expression was associated with poor CD3+ and CD8+ T cell infiltration at baseline. STNM01 led to a significant reduction in CHST15, and increased tumor-infiltrating CD3+ and CD8+ T cells in combination with S-1 at the end of cycle 1. Higher fold increase in CD3+ T cells correlated with longer OS. There were 8 grade 3 adverse events.
UNASSIGNED: Locoregional injection of STNM01 was well tolerated in patients with unresectable PDAC as combined second-line therapy. It prolonged survival by enhancing T cell infiltration in tumor microenvironment.
UNASSIGNED: The present study was supported by the Japan Agency for Medical Research and Development (AMED).
摘要：
未经证实：基质靶向治疗对肿瘤免疫抑制的影响在很大程度上尚未被研究。RNA寡核苷酸，STNM01已显示抑制负责肿瘤蛋白聚糖合成和基质重塑的碳水化合物磺基转移酶15(CHST15)。这项I/IIa期研究旨在评估STNM01在不可切除的胰腺导管腺癌（PDAC）患者中的安全性和有效性。
未经批准：这是一个开放标签，STNM01作为吉西他滨联合nab-紫杉醇难治性PDAC二线治疗的剂量递增研究.一个周期包括三次2周内窥镜超声引导的局部注射STNM01，剂量为250、1,000、2,500或10,000nM，与S-1组合（每天两次80-120mg，每3周14天）。主要结果是剂量-剂量毒性（DLT）的发生率。次要结局包括总生存期（OS），肿瘤反应，肿瘤微环境的变化对免疫组织病理学的影响，和安全性（jRCT2031190055）。
未经批准：共纳入22例患者，最多重复3个循环;未观察到DLT。中位OS为7.8个月。疾病控制率为77.3％；1例患者显示胰腺和肿瘤引流淋巴结可见病变完全消失。较高的肿瘤CHST15表达与基线时较差的CD3+和CD8+T细胞浸润相关。STNM01导致CHST15的显着减少，并在第1周期结束时与S-1组合的肿瘤浸润性CD3和CD8T细胞增加。CD3+T细胞中更高的倍数增加与更长的OS相关。有8个3级不良事件。
UNASSIGNED：局部注射STNM01作为联合二线治疗的不可切除PDAC患者的耐受性良好。它通过增强肿瘤微环境中的T细胞浸润来延长存活。
UNASSIGNED：本研究得到了日本医学研究与发展机构（AMED）的支持。
未经批准：这是一个开放标签，STNM01作为吉西他滨联合nab-紫杉醇难治性PDAC二线治疗的剂量递增研究.一个周期包括三次2周内窥镜超声引导的局部注射STNM01，剂量为250、1,000、2,500或10,000nM，与S-1组合（每天两次80-120mg，每3周14天）。主要结果是剂量-剂量毒性（DLT）的发生率。次要结局包括总生存期（OS），肿瘤反应，肿瘤微环境的变化对免疫组织病理学的影响，和安全性（jRCT2031190055）。
未经批准：共纳入22例患者，最多重复3个循环;未观察到DLT。中位OS为7.8个月。疾病控制率为77.3％；1例患者显示胰腺和肿瘤引流淋巴结可见病变完全消失。较高的肿瘤CHST15表达与基线时较差的CD3+和CD8+T细胞浸润相关。STNM01导致CHST15的显着减少，并在第1周期结束时与S-1组合的肿瘤浸润性CD3和CD8T细胞增加。CD3+T细胞中更高的倍数增加与更长的OS相关。有8个3级不良事件。
UNASSIGNED：局部注射STNM01作为联合二线治疗的不可切除PDAC患者的耐受性良好。它通过增强肿瘤微环境中的T细胞浸润来延长存活。
UNASSIGNED：本研究得到了日本医学研究与发展机构（AMED）的支持。
