Randomized, double-blind, phase III LEAP-003 study of first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab for unresectable or metastatic melanoma.

Here, we report results from LEAP-003 (NCT03820986) which evaluated first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in unresectable advanced melanoma.

在这里，我们报告了LEAP-003研究（NCT03820986）的结果，该研究评估了仑伐替尼联合帕博利珠单抗与安慰剂联合帕博利珠单抗作为一线治疗在不可切除的晚期黑色素瘤中的效果。

participants_and_methods

Participants with unresectable stage III or IV melanoma, previously untreated with PD-(L)1 inhibitors were randomly assigned 1 : 1 to pembrolizumab 200 mg intravenously every 3 weeks plus either lenvatinib 20 mg or placebo orally once daily.

先前未接受PD-(L)1抑制剂治疗的不可切除的III期或IV期黑色素瘤患者，按1:1的比例随机分配，每3周静脉注射200毫克的帕博利珠单抗，同时每天口服20毫克的仑伐替尼或安慰剂。

Dual primary endpoints were progression-free survival(PFS) per RECIST v1.1 by blinded independent central review and overall survival(OS).

主要终点是根据RECIST v1.1标准，由盲法独立中央审查评估的无进展生存期（PFS）和总生存期（OS）。

PFS was formally tested at the first interim analysis; OS at the final analysis.

无进展生存期（PFS）在第一次中期分析时进行了正式测试；总生存期（OS）在最终分析时进行了评估。

An external data monitoring committee regularly reviewed safety and efficacy.

一个外部数据监测委员会定期审查安全性和有效性。

Three interim analyses and a final analysis were planned.

计划进行三次中期分析和一次最终分析。

Results

Overall, 674 participants were assigned to lenvatinib plus pembrolizumab (n = 334) or placebo plus pembrolizumab (n = 340).

总体而言，674名参与者被分配接受仑伐替尼加派姆单抗(n=334)或安慰剂加派姆单抗(n=340)。

Median PFS at first interim analysis was 8.4 months for lenvatinib plus pembrolizumab versus 4.0 months for placebo plus pembrolizumab [hazard ratio(HR) 0.72, 95% confidence interval(CI) 0.59-0.88, P = 0.0008].

首次中期分析显示，仑伐替尼联合派姆单抗的中位无进展生存期为8.4个月，而安慰剂联合派姆单抗为4.0个月[风险比（HR）0.72，95%置信区间（CI）0.59-0.88，P = 0.0008]。

This benefit was not maintained at final analysis (HR 0.83, 95% CI 0.69-1.00).

在最终分析中，这一获益并未得到维持（HR 0.83，95% CI 0.69-1.00）。

Median OS at final analysis was 25.8 months for lenvatinib plus pembrolizumab versus 39.5 months for placebo plus pembrolizumab (HR 1.20, 95% CI 0.97-1.48, P = 0.9521).

在最终分析中，仑伐替尼联合帕博利珠单抗的中位总生存期为25.8个月，而安慰剂联合帕博利珠单抗的中位总生存期为39.5个月（HR 1.20, 95% 置信区间 0.97-1.48, P = 0.9521）。

Grade 3-5 treatment-related adverse events occurred in 58.7% of participants receiving lenvatinib plus pembrolizumab versus 29.0% receiving placebo plus pembrolizumab.

接受仑伐替尼联合帕博利珠单抗治疗的参与者中，3-5级治疗相关不良事件的发生率为58.7%，而接受安慰剂联合帕博利珠单抗治疗的参与者中为29.0%。

Conclusions

Lenvatinib plus pembrolizumab did not provide additional benefit versus placebo plus pembrolizumab in participants with unresectable advanced melanoma.

在不可切除的晚期黑色素瘤患者中，仑伐替尼联合派姆单抗并未比安慰剂联合派姆单抗提供额外的益处。

Thus, the trial was terminated early, and the third interim analysis became the final analysis.

因此，该试验被提前终止，第三次中期分析成为了最终分析。

Immunotherapy remains the standard of care for advanced melanoma.

免疫治疗仍然是晚期黑色素瘤的标准治疗方法。