Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): 4-year outcomes from a double-blind, randomised, phase 3 trial.

We report the 4-year outcomes from this study.

我们报告了这项研究的 4 年结果。

Methods

This randomised, double-blind, phase 3 trial was conducted across 35 hospitals and academic research centres in China.

这项随机、双盲、III期临床试验在中国的35家医院和学术研究中心进行。

Eligible patients were aged 18-75 years; had treatment-naive, histologically or cytologically confirmed stage IV NSCLC, irrespective of PD-L1 expression levels; and had an Eastern Cooperative Oncology Group performance status of 0 or 1.

符合条件的患者年龄在18至75岁之间；为治疗前的患者，经组织学或细胞学证实为IV期非小细胞肺癌（NSCLC），无论PD-L1表达水平如何；并且东部肿瘤协作组（ECOG）的体能状态评分为0或1。

Patients were randomised (2:1) by investigators using an interactive web response or voice response system via permuted blocks (block sizes of three or six, randomised within each stratum).

患者通过交互式网络响应或语音响应系统，使用随机区组法（每个层内随机，区组大小为三或六）进行随机分组（2:1）。

Patients received histology-specific platinum-based chemotherapy combined with either sugemalimab (1200 mg; sugemalimab group) or placebo (placebo group) for up to four cycles, followed by for up to 35 cycles of maintenance therapy with sugemalimab alone for patients with squamous NSCLC and sugemalimab plus pemetrexed for patients with non-squamous NSCLC in the sugemalimab group, or placebo for patients with squamous NSCLC and placebo plus pemetrexed for patients with non-squamous NSCLC in the placebo group, administered intravenously.

患者接受组织学特异性铂类化疗，联合sugemalimab（1200 mg；sugemalimab组）或安慰剂（安慰剂组），最多进行四个周期的治疗，随后对于鳞状非小细胞肺癌（NSCLC）患者，sugemalimab组患者继续接受最多35个周期的sugemalimab单药维持治疗，对于非鳞状NSCLC患者，sugemalimab组患者接受sugemalimab联合培美曲塞维持治疗，而安慰剂组患者则接受安慰剂或安慰剂联合培美曲塞维持治疗，均通过静脉给药。

Treatment beyond 35 cycles was permitted at the investigator's discretion.

研究者可自行决定是否允许超过35个周期的治疗继续进行。

The primary endpoint was investigator-assessed progression-free survivalin the intention-to-treatpopulation.

主要终点是意向治疗人群中研究者评估的无进展生存期。

Here, we report post-hoc 4-year efficacy and safety outcomes from GEMSTONE-302.

在这里，我们报告了GEMSTONE-302研究的4年疗效和安全性事后分析结果。

This study is registered with ClinicalTrials.gov (NCT03789604) and concluded on May 15, 2023, with all patients discontinued.

该研究已在ClinicalTrials.gov上注册（NCT03789604），并已于2023年5月15日结束，所有患者均已停止参与。

Results

Between December 13, 2018, and May 15, 2020, 846 patients were assessed for eligibility. 479 patients were randomly assigned into the sugemalimab group (n=320) and placebo group (n=159). 254 (79%) patients were men and 66 (21%) were women in the sugemalimab group and 129 (81%) were men and 30 (19%) were women in the placebo group.

在2018年12月13日至2020年5月15日期间，共有846名患者被评估是否符合入组资格。其中479名患者被随机分配到sugemalimab组（n=320）和安慰剂组（n=159）。在sugemalimab组中，254名（79%）为男性，66名（21%）为女性；在安慰剂组中，129名（81%）为男性，30名（19%）为女性。

All patients were Asian.

所有患者均为亚洲人。

As of the data cutoff on May 15, 2023, median follow-up durations were 43·5 months (IQR 41·2-46·9) in the sugemalimab group and 43·0 months (40·7-44·8) in the placebo group; median treatment durations were 7·2 months (4·2-18·8) with sugemalimab and 4·6 months (2·8-6·9) with placebo.

截至2023年5月15日数据截止时，sugemalimab组的中位随访时间为43.5个月（四分位数间距41.2-46.9），安慰剂组为43.0个月（四分位数间距40.7-44.8）；sugemalimab的中位治疗时间为7.2个月（四分位数间距4.2-18.8），安慰剂为4.6个月（四分位数间距2.8-6.9）。

Median progression-free survivalwas 9·0 months (95% CI 7·4-10·9) in the sugemalimab group versus 4·9 months (4·8-5·2) in the placebo group (hazard ratio[HR] 0·49 [95% CI 0·39-0·60]).

sugemalimab组的中位无进展生存期为9.0个月（95%置信区间7.4-10.9），而安慰剂组为4.9个月（95%置信区间4.8-5.2）（风险比[HR] 0.49 [95%置信区间0.39-0.60]）。

Median overall survivalwas 25·2 months (20·1-30·2) in the sugemalimab group versus 16·9 months (12·8-20·7) in the placebo group (HR 0·68 [0·54-0·85]).

在sugemalimab组中，中位总生存期为25.2个月（20.1-30.2），而在安慰剂组中为16.9个月（12.8-20.7）（HR 0.68 [0.54-0.85]）。

The 4-year overall survivalrates were 32·1% (95% CI 26·7-37·6) in the sugemalimab group versus 17·3% (11·1-24·7) in the placebo group.

在sugemalimab组中，4年总生存率为32.1%（95%置信区间26.7-37.6），而在安慰剂组中为17.3%（11.1-24.7）。

The most common grade 3-4 treatment related adverse events were decreased neutrophil count (105 [33%] with sugemalimab vs 52 [33%] with placebo), decreased white blood cell count (48 [15%] vs 27 [17%]), anaemia (44 [14%] vs 18 [11%]), and decreased platelet count (35 [11%] vs 15 [9%]).

最常见的3-4级治疗相关不良事件是中性粒细胞减少症（sugemalimab组105例[33%]，安慰剂组52例[33%]），白细胞减少症（48例[15%]对27例[17%]），贫血（44例[14%]对18例[11%]）和血小板减少症（35例[11%]对15例[9%]）。

Treatment-related serious adverse events occurred in 82 (26%) patients with sugemalimab and 31 (20%) with placebo.

与治疗相关的严重不良事件发生在82例（26%）接受sugemalimab治疗的患者和31例（20%）接受安慰剂治疗的患者中。

No additional treatment-related deaths occurred since the previous overall survivalinterim analysis.

自上次总生存期中期分析以来，未发生额外的与治疗相关的死亡事件。

No new safety signals were identified.

未发现新的安全信号。

interpretation

Sugemalimab with chemotherapy showed a superior long-term overall survivalbenefit compared with placebo with chemotherapy, as a first-line treatment for patients with NSCLC with no known sensitising EGFR, ALK, ROS1, or RET genomic alterations.

Sugemalimab联合化疗作为一线治疗方案，对于无已知敏感性EGFR、ALK、ROS1或RET基因组改变的非小细胞肺癌患者，显示出比安慰剂联合化疗更优越的长期总生存益处。

These results underscore the efficacy of sugemalimab plus platinum-based chemotherapy as a standard first-line treatment option for both squamous and non-squamous metastatic NSCLC while maintaining a manageable safety profile.

这些结果强调了sugemalimab联合基于铂类的化疗作为鳞状和非鳞状转移性非小细胞肺癌标准一线治疗选项的有效性，同时保持了可控的安全性特征。

funding

CStone Pharmaceuticals.

基石药业。

translation

For the Chinese translation of the abstract see Supplementary Materials section.

摘要的中文翻译请参见补充材料部分。