Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial.

We report the interim results for the phase 3 RATIONALE-315 study, which aimed to investigate perioperative tislelizumab for the treatment of resectable NSCLC.

我们报告了第三阶段RATIONALE-315研究的中期结果，该研究旨在研究围手术期使用替雷利珠单抗治疗可切除NSCLC。

Methods

RATIONALE-315 is a randomised, double-blind, placebo-controlledphase 3 trial conducted at 50 sites (hospitals or academic research centres) in China.

RATIONALE-315 是一项在中国的 50 个地点（医院或学术研究中心）进行的随机、双盲、安慰剂对照的 III 期试验。

Patients (aged ≥18 years) with untreated stage II-IIIA squamous or non-squamous NSCLC were randomly assigned (1:1) to neoadjuvant tislelizumab 200 mg or placebo intravenously every 3 weeks, plus platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab 400 mg or placebo every 6 weeks.

年龄 ≥18 岁的未接受治疗的 II-IIIA 期鳞状或非鳞状非小细胞肺癌（NSCLC）患者被随机分配（1:1），接受每 3 周一次的静脉注射 200 mg 的替雷利珠单抗或安慰剂，加上基于铂的双药化疗，随后进行手术，并在术后每 6 周接受一次 400 mg 的替雷利珠单抗或安慰剂作为辅助治疗。

Dual primary endpoints were major pathological response rate and event-free survival, analysed by intention to treat.

主要次要终点是主要病理反应率和无事件生存率，通过意向治疗分析。

Safety was also assessed in all patients who received at least one dose of study treatment.

所有接受至少一剂研究治疗的患者的安全性也得到了评估。

RATIONALE-315 is registered with ClinicalTrials.gov, NCT04379635, and is active but not recruiting.

RATIONALE-315已在美国临床试验注册处注册，编号为NCT04379635，目前正在进行中，但不再招募新患者。

Results

Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227).

在2020年6月8日至2022年8月31日期间，共有453名患者被分配至替雷利珠单抗(n=226)或安慰剂(n=227)治疗组。

The median age of patients was 62·0 years (IQR 56·0-67·0). 410 (91%) of 453 patients were male and 43 (9%) were female.

患者的中位年龄为62.0岁（四分位数间距56.0-67.0）。在453名患者中，410名（91%）为男性，43名（9%）为女性。

As of Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 22·0 months (IQR 15·5-28·0).

截至2023年8月21日（无事件生存中期分析的数据截止日期），随访的中位时间为22.0个月（四分位数间距15.5-28.0）。

Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio0·56 [95% CI 0·40-0·79]; one-sided p=0·0003).

Tislelizumab 显著改善了与安慰剂相比的无事件生存期（分层风险比 0·56 [95% 置信区间 0·40-0·79]；单侧 p=0·0003）。

The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50-63]) than in the placebo group (15% [11-20]; difference 41% [33-49]; one-sided p<0·0001).

Tislelizumab 组的主要病理反应率显著高于安慰剂组（56% [95% 置信区间 50-63] 对比 15% [11-20]；差异 41% [33-49]；单侧 p<0·0001）。

Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group.

在 tislelizumab 组的 226 名患者中，有 163 名（72%）发生了 3 级或更严重的不良事件，35 名（15%）发生了严重的治疗相关不良事件；而在安慰剂组中，分别有 150 名（66%）和 18 名（8%）患者发生了这些不良事件。

The most common grade 3 or worse treatment-related adverse eventwas decreased neutrophil count (138 [61%] of 226 in the tislelizumab group vs 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study.

最常见的 3 级或更严重的治疗相关不良事件是中性粒细胞减少症（tislelizumab 组 226 名患者中有 138 名（61%），安慰剂组 226 名患者中有 134 名（59%））。在研究期间，tislelizumab 组有 226 名患者中的 31 名（14%）和安慰剂组有 227 名患者中的 45 名（20%）死亡。

interpretation

Perioperative tislelizumab plus neoadjuvant chemotherapy showed a clinically meaningful and statistically significant improvement in efficacy and a manageable safety profile compared with neoadjuvant chemotherapy in patients with resectable stage II-IIIA NSCLC.

围手术期使用替雷利珠单抗联合新辅助化疗在可切除的II-IIIA期非小细胞肺癌患者中，与单纯新辅助化疗相比，显示出具有临床意义的疗效改善和可管理的安全性特征。

funding

BeiGene.

百济神州。