Subcutaneous versus intravenous nivolumab for renal cell carcinoma.

patients_and_methods

CheckMate 67T (NCT04810078) was a phase III, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20 000 units) or intravenous nivolumab (3 mg/kg every 2 weeks).

CheckMate 67T (NCT04810078) 是一项III期、开放标签、多中心、非劣效试验，其中将晚期/转移性透明细胞肾细胞癌患者随机分为皮下注射纳武利尤单抗（每4周1200毫克；与重组人透明质酸酶PH20 20000单位共配制）或静脉注射纳武利尤单抗（每2周3毫克/公斤）。

The primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis [time-averaged serum concentration over the first 28 days (Cavgd28), and minimum steady-state serum concentration (Cminss); noninferiority threshold: lower boundary of 90% confidence interval(CI) of the geometric mean ratios (GMR) ≥0.8].

主要目标是通过群体药代动力学分析确定的共同主要终点来评估皮下注射与静脉注射纳武利尤单抗的非劣效性[前28天时间平均血清浓度(Cavgd28)和最小稳态血清浓度(Cminss); 非劣效性阈值: 几何平均比率(GMR)的90%置信区间下限≥0.8]。

Objective response rate(ORR) was a key secondary endpoint powered for noninferiority [noninferiority threshold: lower boundary of 95% CI of relative risk of ORR (subcutaneous versus intravenous nivolumab) ≥0.60].

客观缓解率(ORR)是一个关键的次要终点，用于非劣效性检验[非劣效性阈值: ORR相对风险的95%置信区间下限(皮下注射与静脉注射纳武利尤单抗)≥0.60]。

Results

Overall, 495 patients were randomized.

总体而言，共有495名患者被随机分配。

Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of Cavgd28 and Cminss was 2.098 (90% CI 2.001-2.200) and 1.774 (90% CI 1.633-1.927), respectively.

皮下给药组与静脉给药组的相对暴露量，通过Cavgd28和Cminss的几何平均比值（GMR）报告分别为2.098（90%置信区间2.001-2.200）和1.774（90%置信区间1.633-1.927）。

After 8 months of minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI 19.0%-30.0%) versus 18.2% with intravenous nivolumab [95% CI 13.6%-23.6%; relative risk: 1.33 (95% CI 0.94-1.87)].

在至少8个月的随访后，皮下注射纳武利尤单抗的客观缓解率(ORR)为24.2%（95%置信区间19.0%-30.0%），而静脉注射纳武利尤单抗的ORR为18.2%（95%置信区间13.6%-23.6%；相对风险为1.33（95%置信区间0.94-1.87））。

Coprimary endpoints and ORR met noninferiority thresholds.

共同主要终点和ORR均达到了非劣效性标准。

Additional efficacy and safety measures were similar.

其他疗效和安全性指标相似。

Conclusions

Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR.

基于药代动力学和客观缓解率（ORR），皮下注射的纳武利尤单抗在非劣效性上不逊于静脉注射的纳武利尤单抗。

No new safety signals were observed.

未观察到新的安全信号。