PO.CT01.04 · 临床试验
PDR001治疗携带KRAS/NRAS突变或无可靶向遗传学异常的不可切除非小细胞肺癌（NSCLC）患者：II期、多中心、单臂研究
PDR001 in patients with unresectable non-small cell lung cancer (NSCLC) harboring KRAS/NRAS mutation or without actionable genetic abnormalities: Phase II, multicenter, single arm study
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：PDR001（spartalizumab）是一种人源化PD-1阻断抗体，Fc介导的细胞毒性降低。它在多种肿瘤类型中显示出抗肿瘤活性和可控的安全性。本文介绍PDR001治疗无可靶向驱动突变的非小细胞肺癌（NSCLC）患者的结果。
方法：这是一项多中心、开放标签、单臂II期研究。2018年10月5日至2020年12月17日期间，共入组70例无可靶向驱动突变的不可切除NSCLC患者。患者接受PDR001（Spartalizumab）300 mg每3周一次治疗，直至疾病进展或不可耐受的毒性。
结果：中位随访72.0个月（95%置信区间[CI]，72-不可评估）时，中位总生存期为14.0个月（95% CI，10.5-24.1），全部患者的中位PFS为2.8个月（95% CI，1.8-5.9）。疾病控制率和总缓解率分别为61.4%和24.3%。共43例患者可进行PD-L1 TPS分析（采用22C3 IHC），显示PD-L1 TPS≥50%的患者中位OS为16.1个月（95% CI，8.9-46.2），较PD-L1 TPS<50%的患者呈现出更好预后的趋势。TPS≥50%患者的中位PFS较TPS<50%患者显示出显著更好的结果（4.9个月对2.8个月，P=0.038）。共41例患者（58.6%）发生治疗相关不良事件，多数严重程度为1-2级。5例患者发生3级毒性，包括皮疹（n=1）、丙氨酸氨基转移酶升高（n=1）、肺炎（n=1）和高血糖（n=2）。2例患者因不良事件停止治疗：1例因3级皮疹，另1例因3级肺炎。这些AE大多在停药和随后的类固醇治疗后缓解。
结论：PDR001在无可靶向驱动突变的不可切除NSCLC患者中表现出有前景的临床疗效，安全性可耐受。有必要开展未来的随机临床试验以验证我们的发现。
查看英文原文 English abstract
Background: PDR001 (spartalizumab) is a humanized PD-1-blocking antibody with reduced Fc-mediated cytotoxicity. It has shown antitumor activity and manageable safety across multiple tumor types, Herein, we present the results of PDR001 for patients with non-small cell lung cancer (NSCLC) without actionable driver mutations
Methods: This was a multi-center, open-label, single-arm phase II study. A total of 70 patients with unresectable NSCLC without actionable driver mutations were enrolled between October 5, 2018 and December 17, 2020. Patients were treated with PDR001 (Spartalizumab) 300 mg every 3 weeks until disease progression or intolerable toxicity.
Results: At a median follow up of 72.0 months (95% confidence interval [CI], 72 - not evaluable), median overall survival was 14.0 months (95% CI, 10.5 - 24.1), and the median PFS of total patients was 2.8 months (95% CI, 1.8 - 5.9). The disease control rate, and overall response rate was 61.4%, 24.3%, respectively. A total of 43 patients were available for PD-L1 TPS analysis (IHC by 22C3), and patients who showed PD-L1 TPS ≥ 50%, the median OS was 16.1 months (95% CI, 8.9-46.2), which showed trend toward better outcomes compared to patients with PD-L1 TPS < 50%. and median PFS with patients with TPS ≥ 50% showed significantly better outcomes compared to TPS <50% (4.9 months vs. 2.8 months, P = 0.038). A total of 41 patients (58.6%) experienced treatment-related adverse events, the majority of which were grade 1-2 in severity. Grade 3 toxicities occurred in five patients, including rash (n=1), increased alanine aminotransferase (n=1), pneumonitis (n=1), and hyperglycemia (n=2). Two patients discontinued treatment due to adverse events: one because of grade 3 rash and another because of grade 3 pneumonitis. The majority of these AEs resolved upon discontinuation and subsequent steroid treatment.
Conclusions: PDR001 exhibited promising clinical efficacy in patients with unresectable NSCLC without actionable driver mutations, exhibited tolerable safety. Future randomized clinical trials are warranted to validate our findings.
利益披露 Disclosure
Y. Bang, None..
S. Kim, None..
S. Yoon, None..
D. Lee, None..
B. Keam, None..
D. Kim, None..
S. Kim, None.