易普利姆玛 (IPI) 与纳武单抗 (NIVO) 联合使用，是经批准的针对中危或低危晚期肾细胞癌 (aRCC) 患者的一线治疗选择。我们进行了一项随机 II 期试验，以评估每 12 周一次（修改）而不是每 3 周一次（标准）给药 IPI 与 NIVO 联用是否与良好的毒性特征相关。 aRCC 细胞按 2:1 随机分配，接受四剂改良或标准 IPI（1 mg/kg）与 NIVO（3 mg/kg）联合治疗。主要终点是接受至少一剂治疗的患者中出现 3-5 级治疗相关不良事件 (trAE) 的患者比例。关键的次要终点是改良组与历史舒尼替尼对照相比的 12 个月无进展生存期 (PFS)。该研究的目的并不是正式比较各组的疗效。2018 年 3 月至 2020 年 1 月期间，192 名患者（69.8% 中度/低风险）被随机分配并接受至少一剂研究药物。接受改良 IPI 的参与者与接受标准 IPI 的参与者相比，3-5 级 trAE 的发生率显着降低（32.8% vs 53.1%；比值比，0.43 [90% CI，0.25 至 0.72]；P = 0.0075）。使用改良 IPI 的 12 个月 PFS (90% CI) 为 46.1%（38.6 至 53.2）。中位随访 21 个月时，改良 IPI 组和标准 IPI 组的总体有效率分别为 45.3% 和 35.9%，中位 PFS 分别为 10.8 个月和 9.8 个月。 3-5 级 trAE 发生率显着降低接受改良 IPI 与标准 IPI 的患者。尽管与历史对照相比，12 个月 PFS 未达到预先设定的疗效阈值，但治疗组的非正式比较并未表明修改后的治疗方案的疗效有任何降低。

Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved frontline treatment option for patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to evaluate whether administering IPI once every 12 weeks (modified), instead of once every 3 weeks (standard), in combination with NIVO, is associated with a favorable toxicity profile.Treatment-naïve patients with clear-cell aRCC were randomly assigned 2:1 to receive four doses of modified or standard IPI, 1 mg/kg, in combination with NIVO (3 mg/kg). The primary end point was the proportion of patients with a grade 3-5 treatment-related adverse event (trAE) among those who received at least one dose of therapy. The key secondary end point was 12-month progression-free survival (PFS) in the modified arm compared with historical sunitinib control. The study was not designed to formally compare arms for efficacy.Between March 2018 and January 2020, 192 patients (69.8% intermediate/poor-risk) were randomly assigned and received at least one dose of study drug. The incidence of grade 3-5 trAEs was significantly lower among participants receiving modified versus standard IPI (32.8% v 53.1%; odds ratio, 0.43 [90% CI, 0.25 to 0.72]; P = .0075). The 12-month PFS (90% CI) using modified IPI was 46.1% (38.6 to 53.2). At a median follow-up of 21 months, the overall response rate was 45.3% versus 35.9% and the median PFS was 10.8 months versus 9.8 months in the modified and standard IPI groups, respectively.Rates of grade 3-5 trAEs were significantly lower in patients receiving modified versus standard IPI. Although 12-month PFS did not meet the prespecified efficacy threshold compared with historical control, informal comparison of treatment groups did not suggest any reduction in efficacy with the modified schedule.