PDF(Pubmed)
Abstract：
UNASSIGNED: The open-label, phase II RATIONALE-209 study evaluated tislelizumab (anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) tumors.
UNASSIGNED: Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate (ORR; primary endpoint), duration of response (DoR), and progression-free survival (PFS) were assessed by independent review committee (Response Evaluation Criteria in Solid Tumors v1.1).
UNASSIGNED: Eighty patients were enrolled and treated; 75 (93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease (n=79; 98.8%). At primary analysis (data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval (95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal (n=46): 39.1% (95% CI, 25.1-54.6); gastric/gastroesophageal junction (n=9): 55.6% (95% CI, 21.2-86.3); others (n=20): 60.0% (95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five (6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up (data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.
UNASSIGNED: Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
UNASSIGNED: Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate (ORR; primary endpoint), duration of response (DoR), and progression-free survival (PFS) were assessed by independent review committee (Response Evaluation Criteria in Solid Tumors v1.1).
UNASSIGNED: Eighty patients were enrolled and treated; 75 (93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease (n=79; 98.8%). At primary analysis (data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval (95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal (n=46): 39.1% (95% CI, 25.1-54.6); gastric/gastroesophageal junction (n=9): 55.6% (95% CI, 21.2-86.3); others (n=20): 60.0% (95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five (6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up (data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.
UNASSIGNED: Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
摘要：
■开放标签，II期RATIONALE-209研究评估了tislelizumab(抗程序性细胞死亡蛋白1抗体)作为微卫星不稳定性高(MSI-H)/错配修复缺陷(dMMR)肿瘤的组织不可知单药治疗.
■曾接受过治疗的成年人，纳入局部晚期不可切除或转移性MSI-H/dMMR实体瘤.患者每3周静脉注射tislelizumab200mg。客观缓解率（ORR；主要终点），响应持续时间(DoR)，和无进展生存期(PFS)由独立审查委员会进行评估(实体瘤反应评估标准1.1版).
■80例患者被纳入并接受治疗；75例（93.8%）患者在基线时具有可测量的疾病。大多数患有转移性疾病，并接受了至少一种晚期/转移性疾病的先前治疗（n=79;98.8%）。在初步分析(数据截止时间2021年7月8日；中位随访15.2个月)，总体ORR[46.7%；95%置信区间（95%CI），35.1-58.6；单侧P<0.0001]，肿瘤特异性亚组的ORR[结直肠（n=46）：39.1％（95％CI，25.1-54.6）；胃/胃食管交界处（n=9）：55.6％（95％CI，21.2-86.3）；其他（n=20）：60.0％（95％CI，36.1-80.9）]预设的历史对照ORR为10%;5例(6.7%)患者完全缓解.中位数DoR,PFS,长期随访未达到总生存期(数据截止时间2022年12月5日;中位随访28.9个月).Tislelizumab耐受性良好，没有意外的安全信号。53.8%的患者发生≥3级的治疗相关不良事件（TRAEs）；7.5%的患者因TRAEs而停止治疗。
■Tislelizumab在以前接受过治疗的患者中显示出显着的ORR改善，局部晚期不可切除或转移性MSI-H/dMMR肿瘤，通常耐受性良好。
■曾接受过治疗的成年人，纳入局部晚期不可切除或转移性MSI-H/dMMR实体瘤.患者每3周静脉注射tislelizumab200mg。客观缓解率（ORR；主要终点），响应持续时间(DoR)，和无进展生存期(PFS)由独立审查委员会进行评估(实体瘤反应评估标准1.1版).
■80例患者被纳入并接受治疗；75例（93.8%）患者在基线时具有可测量的疾病。大多数患有转移性疾病，并接受了至少一种晚期/转移性疾病的先前治疗（n=79;98.8%）。在初步分析(数据截止时间2021年7月8日；中位随访15.2个月)，总体ORR[46.7%；95%置信区间（95%CI），35.1-58.6；单侧P<0.0001]，肿瘤特异性亚组的ORR[结直肠（n=46）：39.1％（95％CI，25.1-54.6）；胃/胃食管交界处（n=9）：55.6％（95％CI，21.2-86.3）；其他（n=20）：60.0％（95％CI，36.1-80.9）]预设的历史对照ORR为10%;5例(6.7%)患者完全缓解.中位数DoR,PFS,长期随访未达到总生存期(数据截止时间2022年12月5日;中位随访28.9个月).Tislelizumab耐受性良好，没有意外的安全信号。53.8%的患者发生≥3级的治疗相关不良事件（TRAEs）；7.5%的患者因TRAEs而停止治疗。
■Tislelizumab在以前接受过治疗的患者中显示出显着的ORR改善，局部晚期不可切除或转移性MSI-H/dMMR肿瘤，通常耐受性良好。
