KEYNOTE-025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1-positive advanced non-small-cell lung cancer
KEYNOTE-025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1-positive advanced non-small-cell lung cancer
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DOI：
10.1111/cas.13932
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发表时间：
2019-03-01
期刊：
影响因子：
5.7
通讯作者：
Kato, Terufumi
中科院分区：
文献类型：
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作者：
Nishio, Makoto;Takahashi, Toshiaki;Kato, Terufumi
Pembrolizumab是一种针对程序性死亡1 （PD-1）的人源化单克隆抗体，已被证明可改善先前治疗过的程序性死亡配体1 （PD-L1）肿瘤比例评分(TPS) >= 1%的晚期非小细胞肺癌（NSCLC）患者的总生存期（OS）。我们报告1b期KEYNOTE-025研究的安全性和有效性结果，该研究评估了派姆单抗在日本既往治疗过的NSCLC患者中的应用。符合条件的患者经组织学/细胞学证实为晚期NSCLC， PD-L1 TPS >= 1%，并接受了>= 1铂双药化疗。患者接受pembrolizumab 10mg /kg治疗，每3周1次，持续2年或直到疾病进展/不可接受的毒性。主要目的是评估pembrolizumab在PD-L1 TPS >= 1%的患者中的安全性，以及PD-L1 TPS >= 50%的患者中根据RECIST 1.1版本的客观缓解率（ORR）。38例患者接受了>= 1剂量的派姆单抗治疗。中位（范围）年龄为66.0（41-78）岁，61%既往接受过>= 2的全身治疗。11例患者（29%）出现3-5级治疗相关不良事件（AE）；9名患者（24%）经历了免疫介导的AE和输液反应，其中肺炎（11%，任何级别）最常见。在可评估的PD-L1 TPS患者中，>= 50% (n = 11)， ORR为27% （95% CI, 6-61）。在可评估的PD-L1 TPS患者中，>= 1% (n = 37)， ORR为22% （95% CI, 10-38）。中位无进展生存期（95% CI）和OS分别为3.9（2.0-6.2）个月和19.2（8.0-26.7）个月。综上所述，pembrolizumab在日本既往治疗过的pd - l1表达的NSCLC患者中具有良好的耐受性，并显示出良好的抗肿瘤活性。结果与KEYNOTE-010期研究的结果一致。（试验注册号：ClinicalTrials.gov, NCT02007070.）
Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), has been shown to improve overall survival (OS) in patients with previously treated advanced non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) >= 1%. We report safety and efficacy results from the phase 1b KEYNOTE-025 study, which evaluated pembrolizumab in Japanese patients with previously treated NSCLC. Eligible patients had histologically/cytologically confirmed advanced NSCLC with PD-L1 TPS >= 1% and had received >= 1 platinum-doublet chemotherapy. Patients received pembrolizumab 10 mg/kg once every 3 weeks for 2 years or until disease progression/unacceptable toxicity. Primary objectives were to evaluate the safety of pembrolizumab in patients with PD-L1 TPS >= 1% and the objective response rate (ORR) per RECIST version 1.1 in patients with PD-L1 TPS >= 50%. Thirty-eight patients were enrolled and received >= 1 pembrolizumab dose. The median (range) age was 66.0 (41-78) years, and 61% had received >= 2 prior systemic therapies. Eleven patients (29%) experienced grade 3-5 treatment-related adverse events (AE); 9 patients (24%) experienced immune-mediated AE and infusion reactions, with pneumonitis (11%; any grade) being most common. Among evaluable patients with PD-L1 TPS >= 50% (n = 11), ORR was 27% (95% CI, 6-61). Among evaluable patients with PD-L1 TPS >= 1% (n = 37), ORR was 22% (95% CI, 10-38). Median (95% CI) progression-free survival and OS were 3.9 (2.0-6.2) months and 19.2 (8.0-26.7) months, respectively. In summary, pembrolizumab was generally well tolerated and showed promising antitumor activity in Japanese patients with previously treated PD-L1-expressing NSCLC. Outcomes were consistent with those from the phase 3 KEYNOTE-010 study. (Trial registration number: ClinicalTrials.gov, NCT02007070.)