Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.
Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.
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DOI：
10.1200/jco.2014.59.0703
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发表时间：
2015-05-01
期刊：
影响因子：
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通讯作者：
Hammers HJ
中科院分区：
文献类型：
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作者：
Motzer RJ;Rini BI;McDermott DF;Redman BG;Kuzel TM;Harrison MR;Vaishampayan UN;Drabkin HA;George S;Logan TF;Margolin KA;Plimack ER;Lambert AM;Waxman IM;Hammers HJ
Nivolumab是一种完全人类免疫球蛋白G4程序性死亡-1免疫检查点抑制抗体，可恢复T细胞免疫活性。这项II期试验评估了nivolumab在转移性肾细胞癌(MRCC)患者中的抗肿瘤活性、剂量反应关系和安全性。以前接受过针对血管内皮生长因子途径的药物治疗的透明细胞肾癌患者被随机分配(盲法比率为1：1：1)，每3周静脉注射一次尼伏卢单抗0.3、2或10 mg/kg。主要目的是通过无进展生存期(PFS)来评估剂量-反应关系；次要终点包括客观反应率(ORR)、总生存期(OS)和安全性。共有168名患者被随机分配到nivolumab 0.3-(n=60)、2-(n=54)和10-mg/kg(n=54)队列中。118名患者(70%)之前接受过一种以上的全身治疗方案。中位PFS分别为2.7个月、4.0个月和4.2个月(P=0.9)。OR值分别为20%、22%和20%。中位OS分别为18.2个月(80%CI，16.2~24.0个月)、25.5个月(80%CI，19.8~28.8个月)和24.7个月(80%CI，15.3~26.0个月)。最常见的治疗相关不良事件(AE)是疲劳(分别为24%、22%和35%)。19名患者(11%)经历了3-4级与治疗相关的AEs。在mRCC研究的三种剂量中，nivolumab显示出抗肿瘤活性，安全性可控。PFS检测未发现剂量-反应关系。这些有效性和安全性导致了第三阶段环境下的mRCC支持研究。
Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting.