Vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB-IV melanoma (KEYVIBE-010): a randomised, double-blind, phase 3 study.

We aimed to evaluate the efficacy and safety of vibostolimab coformulated with pembrolizumab as adjuvant therapy for high-risk resected melanoma.

我们的目标是评估vibostolimab与pembrolizumab联合制剂作为高危切除黑色素瘤辅助治疗的疗效和安全性。

Methods

This randomised, double-blind, phase 3 study was done at 205 global sites (hospitals and cancer centres).

这是一项随机、双盲、第三阶段的研究，在全球205个地点（医院和癌症中心）进行。

Participants aged 12 years or older with surgically resected, stage IIB-IV cutaneous melanoma per the American Joint Committee on Cancer Cancer Staging Manual 2017 (8th edition), with no evidence of metastatic disease after resection, were randomly assigned (1:1) to receive vibostolimab 200 mg coformulated with pembrolizumab 200 mg or pembrolizumab 200 mg alone intravenously every 3 weeks.

年龄在12岁或以上的参与者，根据美国癌症联合委员会癌症分期手册2017年版（第8版），患有IIB-IV期皮肤黑色素瘤，且在切除后没有转移性疾病的证据，被随机分配（1:1）接受每3周静脉注射200毫克的vibostolimab与200毫克的pembrolizumab共配制剂，或单独接受200毫克的pembrolizumab。

Randomisation was done using an interactive response technology system and was stratified by risk-based staging and geographical region.

使用交互式响应技术系统进行随机分组，并根据基于风险的分期和地理区域进行分层。

Participants, investigators, and site staff were masked to group assignment.

参与者、研究者和现场工作人员对组别分配情况进行了盲法处理。

The primary endpoint was recurrence-free survival assessed in the intention-to-treatpopulation.

主要终点是在意向治疗人群中评估的无复发生存期。

Safety was assessed in all participants who received at least one dose of the study treatment.

安全性评估是在所有至少接受一次研究治疗的参与者中进行的。

The protocol-prespecified first interim analysis was an event-driven nonbinding futility analysis of recurrence-free survival that was planned for when 111 events had occurred (futility bar of observed HR 0·95).

预先设定的首次中期分析是一项基于事件驱动的非约束性无效果分析，计划在发生111起事件时进行（无效果界限观察到的HR为0·95）。

This study is registered with ClinicalTrials.gov (NCT05665595), and is closed to recruitment.

这项研究已在ClinicalTrials.gov注册（NCT05665595），目前招募已关闭。

Results

Between Jan 19, 2023, and March 6, 2024, 1402 participants were randomly assigned to receive coformulated vibostolimab-pembrolizumab (n=701) or pembrolizumab (n=701).

在2023年1月19日至2024年3月6日期间，共有1402名参与者被随机分配接受复方制剂vibostolimab-pembrolizumab（n=701）或pembrolizumab（n=701）。

At the first interim analysis, median study follow-up, defined as time from randomisation to data cutoff, was 4·2 months (IQR 1·9-6·7).

在首次中期分析中，研究的中位随访时间，定义为从随机分组到数据截止的时间，为4.2个月（四分位数间距1.9-6.7）。

The median age was 61·0 years (IQR 51·0-70·0), 829 (59%) of 1402 participants were male and 573 (41%) were female. 1107 (79%) of participants were White, 273 (19%) were Asian, and 22 (2%) were of other race or race was missing.

中位年龄为61.0岁（四分位数间距51.0-70.0），1402名参与者中有829名（59%）为男性，573名（41%）为女性。1107名（79%）参与者为白人，273名（19%）为亚洲人，22名（2%）为其他种族或种族信息缺失。

At the time of the first interim analysis, a total of 119 (8%) of 1402 participants had had a recurrence-free survival event, including 67 (10%) of 701 in the vibostolimab-pembrolizumab group and 52 (7%) of 701 in the pembrolizumab alone group.

在第一次中期分析时，1402名参与者中共有119名（8%）发生了无复发生存事件，其中vibostolimab-pembrolizumab组的701名参与者中有67名（10%）发生事件，而仅接受pembrolizumab治疗的701名参与者中有52名（7%）发生事件。

The median recurrence-free survival was not reached in either group; the hazard ratiofor recurrence-free survival in the vibostolimab-pembrolizumab group versus pembrolizumab alone group was 1·25 (95% CI 0·9-1·8).

两组的中位无复发生存期均未达到；vibostolimab联合pembrolizumab组与单独使用pembrolizumab组的无复发生存风险比为1.25（95%置信区间0.9-1.8）。

The most common (occurred in more than five participants) grade 3 or higher treatment-related adverse events were adrenal insufficiency in 13 (2%) participants, hepatitis in 11 (2%) participants, rash in 9 (1%) participants, maculopapular rash in 7 (1%) participants, and pruritus in 6 (1%) participants in the vibostolimab-pembrolizumab group and increased alanine aminotransferase in 7 (1%) participants in the pembrolizumab alone group.

最常见的（发生在超过五名参与者中）3级或更高级别的治疗相关不良事件，在vibostolimab-pembrolizumab组中，肾上腺功能不全发生在13名（2%）参与者中，肝炎发生在11名（2%）参与者中，皮疹发生在9名（1%）参与者中，斑丘疹发生在7名（1%）参与者中，瘙痒发生在6名（1%）参与者中；而在单独使用pembrolizumab组中，丙氨酸氨基转移酶升高发生在7名（1%）参与者中。

Treatment-related serious adverse events occurred in 74 (11%) participants and 30 (4%) participants, respectively.

治疗相关的严重不良事件分别发生在74名（11%）和30名（4%）参与者中。

Treatment-related adverse events led to death in two (<1%) participants in the vibostolimab-pembrolizumab group (myasthenia gravis and myocarditis) and one participant (<1%) in the pembrolizumab group (myositis).

治疗相关的不良事件导致 vibostolimab-pembrolizumab 组中2名（<1%）参与者死亡（肌无力和心肌炎），以及 pembrolizumab 组中1名（<1%）参与者死亡（肌炎）。

The external data monitoring committee decided to discontinue the study according to prespecified futility criteria.

外部数据监测委员会根据预先设定的无效性标准决定终止研究。

interpretation

Vibostolimab coformulated with pembrolizumab did not provide additional clinical benefit versus pembrolizumab as adjuvant therapy in participants with resected stage IIB-IV melanoma.

Vibostolimab与帕博利珠单抗联合制剂作为辅助治疗，并未在II B-IV期切除性黑色素瘤患者中提供额外的临床益处，与单独使用帕博利珠单抗相比。

Pembrolizumab monotherapy remains a standard of care for resected high-risk melanoma.

Pembrolizumab单药治疗仍然是切除高风险黑色素瘤的标准治疗。

funding

Merck Sharp & Dohme, a subsidiary of Merck & Co.

默克夏普与多姆公司是默克公司的子公司。