Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma.

The hypoxia-inducible factor 2α inhibitor belzutifan has activity in advanced disease.

低氧诱导因子2α抑制剂Belzutifan在晚期疾病中具有活性。

Adjuvant pembrolizumab with belzutifan may further improve outcomes in patients with clear-cell renal-cell carcinoma at increased risk for recurrence.

辅助性帕博利珠单抗联合贝尔祖替芬可能进一步改善高复发风险的透明细胞肾细胞癌患者的预后。

Methods

In this phase 3, double-blindtrial, we randomly assigned participants in a 1:1 ratio to receive intravenous pembrolizumab at a dose of 400 mg every 6 weeks (≤9 doses) and either daily oral belzutifan at a dose of 120 mg (pembrolizumab-belzutifan) or placebo (pembrolizumab-placebo) for up to 1 year.

在这项III期、双盲试验中，我们以1:1的比例随机分配参与者，接受静脉注射帕博利珠单抗，剂量为每6周400毫克（最多9剂），并同时每天口服贝尔祖替芬120毫克（帕博利珠单抗-贝尔祖替芬组）或安慰剂（帕博利珠单抗-安慰剂组），持续时间最多为1年。

The primary end point was disease-free survival as assessed by the investigator; secondary end points included overall survivaland safety.

主要终点是研究者评估的无病生存期；次要终点包括总生存和安全性。

Results

A total of 921 participants were assigned to receive pembrolizumab-belzutifan and 920 were assigned to receive pembrolizumab-placebo.

共有921名参与者被分配接受派姆单抗-贝佐替凡治疗，920名被分配接受派姆单抗-安慰剂治疗。

The median time from randomization to the data-cutoff date (August 23, 2025) was 28.4 months (range, 15.0 to 40.1).

从随机化到数据截止日期（2025年8月23日）的中位时间是28.4个月（范围，15.0至40.1个月）。

Disease-free survival was significantly higher with pembrolizumab-belzutifan than with pembrolizumab-placebo (hazard ratiofor disease recurrence or death, 0.72; 95% confidence interval[CI], 0.59 to 0.87; two-sided P<0.001); the estimated 24-month disease-free survival was 80.7% and 73.7%, respectively.

与帕博利珠单抗安慰剂相比，帕博利珠单抗-贝祖替凡的无病生存率显著更高（疾病复发或死亡的风险比为0.72；95%置信区间[CI]，0.59至0.87；双侧P<0.001）；估计的24个月无病生存率分别为80.7%和73.7%。

At this interim analysis with 29% of the final-analysis events observed, overall survivaldid not differ significantly between the groups (hazard ratiofor death, 0.78; 95% CI, 0.51 to 1.19; two-sided P = 0.24); the estimated 24-month overall survivalwas 96.2% with pembrolizumab-belzutifan and 95.7% with pembrolizumab-placebo.

在这次中期分析中，观察到最终分析事件的29%，两组之间的总生存没有显著差异（死亡风险比为0.78；95%置信区间，0.51至1.19；双侧P=0.24）；预计24个月的总生存率在pembrolizumab-belzutifan组为96.2%，在pembrolizumab-placebo组为95.7%。

Adverse events of grade 3 or higher occurred in 52.1% of the participants who received pembrolizumab-belzutifan and in 30.2% of those who received pembrolizumab-placebo.

在接受pembrolizumab-belzutifan治疗的参与者中，有52.1%出现了3级或更高级别的不良事件，在接受pembrolizumab-placebo治疗的参与者中，这一比例为30.2%。

Conclusions

Treatment with pembrolizumab-belzutifan led to significantly higher disease-free survival, with a greater risk of grade 3 or higher toxic effects, than treatment with pembrolizumab monotherapy after nephrectomy in participants with clear-cell renal-cell carcinoma at increased risk for recurrence.

与单纯使用帕博利珠单抗治疗相比，接受帕博利珠单抗-贝佐替凡治疗的患者在肾切除术后，对于复发风险增加的透明细胞肾细胞癌患者，无病生存期显著更长，但3级或更高级别的不良反应风险也更大。

(Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; LITESPARK-022 ClinicalTrials.gov number, NCT05239728.).

(该研究由默克夏普和多姆公司资助，为默克公司[新泽西州拉霍伊]的子公司；LITESPARK-022临床试验注册号，NCT05239728。)