Benmelstobart plus anlotinib versus pembrolizumab as first-line treatment for PD-L1-positive, advanced non-small-cell lung cancer (CAMPASS): a blinded, randomised, controlled, phase 3 trial.

We aimed to compare benmelstobart plus anlotinib with pembrolizumab in patients with previously untreated, driver gene-negative, PD-L1-positive, advanced NSCLC.

我们的目标是比较benmelstobart联合anlotinib与pembrolizumab在之前未接受治疗、驱动基因阴性、PD-L1阳性、晚期NSCLC患者中的效果。

Methods

The blinded, randomised, controlled, phase 3 CAMPASS trial was conducted in 79 centres across China.

在中国的79个中心进行了盲法、随机、对照的CAMPASS III期试验。

Patients aged 18-75 years with stage IIIB-IV squamous or non-squamous NSCLC, no previous systemic treatment for advanced, recurrent or metastatic diseases, a PD-L1 tumour proportion score of 1% or greater, a life expectancy of 3 months or longer, at least one measurable lesion, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (2:1) to receive intravenous benmelstobart (1200 mg once on day 1) plus oral anlotinib (12 mg daily on days 1-14) or intravenous pembrolizumab (200 mg once on day 1) plus placebo every 3 weeks.

年龄在18-75岁之间，患有IIIB-IV期鳞状或非鳞状非小细胞肺癌（NSCLC），之前未接受过针对晚期、复发或转移性疾病的全身治疗，PD-L1肿瘤比例分数为1%或以上，预期寿命为3个月或更长，至少有一个可测量的病灶，以及东部肿瘤协作组（Eastern Cooperative Oncology Group）表现状态为0或1的患者，按照2:1的比例随机分配接受静脉注射benmelstobart（第1天1200毫克一次）加上口服anlotinib（第1-14天每天12毫克）或静脉注射pembrolizumab（第1天200毫克一次）加上安慰剂，每3周一次。

Randomisation was done centrally and stratified by tumour histology, PD-L1 tumour proportion score, and brain metastases.

随机化是通过中心进行的，并根据肿瘤组织学、PD-L1肿瘤比例评分和脑转移进行分层。

Treatment allocation was open label for investigators and masked to patients and statisticians.

治疗分配对研究者是开放标签的，对患者和统计学家是盲法的。

The primary endpoint was progression-free survivalas assessed by a blinded independent review committee per Response Evalutation Criteria in Solid Tumours version 1.1 in the intention-to-treatpopulation (all randomly assigned patients).

主要终点是根据实体瘤疗效评价标准第1.1版，由盲态独立评审委员会评估的无进展生存期，在意向治疗人群中（所有随机分配的患者）进行评估。

Safety was assessed in all randomly assigned patients who received at least dose of study drug.

在所有至少接受了一次研究药物剂量的随机分配患者中评估安全性。

Results reported here are from a preplanned final analysis for progression-free survival. This ongoing study is closed to recruitment and is registered with ClinicalTrials.gov, NCT04964479.

这里报告的结果是基于预先计划的无进展生存期的最终分析。这项正在进行的研究已经停止招募，并已在ClinicalTrials.gov上注册，注册号为NCT04964479。

Results

Between Aug 6, 2021, and Dec 14, 2022, 531 patients were randomly assigned (354 to the benmelstobart plus anlotinib group and 177 to the pembrolizumab plus placebo group). 449 (85%) patients were male, 82 (15%) were female, and 493 (93%) were of Han ethnicity.

从2021年8月6日到2022年12月14日，共有531名患者被随机分配（354名患者分配至苯美司他加阿诺替尼组，177名患者分配至帕博利珠单抗加安慰剂组）。其中449名（85%）患者为男性，82名（15%）为女性，493名（93%）为汉族。

Two patients in the benmelstobart plus anlotinib group and one patients in the pembrolizumab plus placebo group were untreated and therefore excluded from the safety population.

在benmelstobart联合anlotinib组中有两名患者和在pembrolizumab联合安慰剂组中有一名患者未接受治疗，因此被排除在安全性人群之外。

After a median follow-up of 11·4 months (95% CI 9·4-13·1) for the benmelstobart plus anlotinib group and 10·6 months (9·0-13·0) for the pembrolizumab plus placebo group, median progression-free survivalwas 11·0 months (9·2-12·6) and 7·1 months (5·8-9·5), respectively (hazard ratio[HR] 0·70 [95% CI 0·54-0·90]; log-rank p=0·0057).

在benmelstobart联合anlotinib组中位随访时间为11.4个月（95%置信区间9.4-13.1），在pembrolizumab联合安慰剂组中位随访时间为10.6个月（95%置信区间9.0-13.0），中位无进展生存期分别为11.0个月（95%置信区间9.2-12.6）和7.1个月（95%置信区间5.8-9.5）（风险比[HR] 0.70 [95%置信区间0.54-0.90]；对数秩检验p=0.0057）。

Grade 3 or worse treatment-related adverse events occurred in 206 (59%) of 352 patients in the benmelstobart plus anlotinib group and 51 (29%) of 176 patients in the pembrolizumab plus placebo group, and the most frequent one was hypertension (90 [26%] vs five [3%]).

在接受贝美替尼加阿诺替尼治疗的352名患者中，有206名（59%）出现了3级或更严重的治疗相关不良事件，而在接受帕博利珠单抗加安慰剂治疗的176名患者中，有51名（29%）出现了3级或更严重的治疗相关不良事件，其中最常见的是高血压（90名[26%]对比五名[3%]）。

Serious treatment-related adverse events occurred in 89 (25%) patients in the benmelstobart plus anlotinib group and 37 (21%) patients in the pembrolizumab plus placebo group, the most common of which were haemoptysis (nine [3%] vs none) and immune-mediated pulmonary diseases (eight [2%] vs five [3%]).

在贝美替尼加阿诺替尼组中有89名（25%）患者出现了严重的治疗相关不良事件，在帕博利珠单抗加安慰剂组中有37名（21%）患者出现了严重的治疗相关不良事件，其中最常见的分别是咯血（九名[3%]对比无）和免疫介导的肺部疾病（八名[2%]对比五名[3%]）。

Five (1%) treatment-related deaths occurred in the benmelstobart plus anlotinib group (two due to haemoptysis and one each due to immune-mediated pulmonary disease, disease progression, and infection pneumonia) and four (2%) occurred in the pembrolizumab plus placebo group (one each due to respiratory failure, pulmonary inflammation, disease progression, and myocardial injury).

在benmelstobart联合anlotinib组中发生了五例（1%）与治疗相关的死亡（两例由于咯血，一例由于免疫介导的肺部疾病，疾病进展和感染性肺炎），而在pembrolizumab联合安慰剂组中发生了四例（2%）（各一例由于呼吸衰竭，肺部炎症，疾病进展和心肌损伤）。

interpretation

Benmelstobart plus anlotinib showed longer progression-free survivalthan pembrolizumab plus placebo and no unexpected safety signals were reported, suggesting benmelstobart plus anlotinib as a potential first-line option in driver gene-negative, PD-L1-positive, advanced NSCLC.

Benmelstobart联合anlotinib显示出比pembrolizumab联合安慰剂更长的无进展生存期，并且没有报告出意外的安全信号，这表明benmelstobart联合anlotinib可能是驱动基因阴性、PD-L1阳性、晚期非小细胞肺癌的一线治疗选择。

Longer term follow-up is needed to establish effects on overall survival.

需要更长期的随访来确定对总生存的影响。

funding

Chia Tai Tianqing Pharmaceutical Group.

正大天晴药业集团。