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).
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。