Tiragolumab Plus Atezolizumab and Chemotherapy for Advanced Nonsquamous Non-Small Cell Lung Cancer: The Phase 3 SKYSCRAPER-06 Randomized Clinical Trial.

Background

To evaluate the efficacy and safety of tiragolumab plus atezolizumab plus chemotherapy vs placebo plus pembrolizumab plus chemotherapy in patients with advanced nonsquamous NSCLC.

评估tiragolumab联合atezolizumab及化疗与安慰剂联合pembrolizumab及化疗在晚期非鳞状NSCLC患者中的疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS: SKYSCRAPER-06 was a phase 3 randomized clinical trial that recruited patients with previously untreated, locally advanced unresectable or metastatic NSCLC at 129 sites in 21 countries between December 15, 2020, and September 14, 2023 (data cutoff, April 19, 2024).

设计、设置和参与者：SKYSCRAPER-06是一项III期随机临床试验，招募了2020年12月15日至2023年9月14日期间（数据截止日期为2024年4月19日），在21个国家的129个地点的先前未接受治疗的局部晚期不可切除或转移性非小细胞肺癌患者。

intervention

Patients were randomized 1:1 to receive either tiragolumab, 600 mg, plus atezolizumab, 1200 mg, plus chemotherapy (pemetrexed, 500 mg/m2, and carboplatin [area under the curve 5], or cisplatin, 75 mg/m2) or placebo plus pembrolizumab, 200 mg, plus chemotherapy via intravenous infusion on day 1 of each 21-day cycle until disease progression, loss of clinical benefit, unacceptable toxic effect, or withdrawal of consent.

患者按1:1的比例随机接受tiragolumab 600 mg加atezolizumab 1200 mg加化疗（培美曲塞500 mg/m2和卡铂[曲线下面积5]或顺铂75 mg/m2）或安慰剂加pembrolizumab 200 mg加化疗，每21天为一个周期，在第1天通过静脉输注，直至疾病进展、临床获益丧失、不可接受的毒性反应或撤回同意。

main_outcomes_and_measures

Primary end points were investigator-assessed progression-free survivaland overall survival. The safety and tolerability of the study drugs were also evaluated.

主要终点是研究者评估的无进展生存期和总生存期。同时评估了研究药物的安全性和耐受性。

Results

Of 542 patients in the full analysis set (mean [SD] age, 63.6 [9.3] years; 353 [65.1%] male), 269 were randomized to tiragolumab plus atezolizumab plus chemotherapy and 273 to placebo plus pembrolizumab plus chemotherapy.

在全分析集中的542名患者（平均年龄[标准差]为63.6[9.3]岁；353名[65.1%]为男性）中，有269名被随机分配至tiragolumab联合atezolizumab联合化疗组，273名被随机分配至安慰剂联合pembrolizumab联合化疗组。

Overall, baseline demographics were similar between treatment groups.

总体而言，治疗组之间的基线人口统计数据相似。

At data cutoff (median follow-up, 11.8 months), median investigator-assessed progression-free survivalwas 8.3 months (95% CI, 7.1-9.6 months) with tiragolumab plus atezolizumab plus chemotherapy vs 9.9 months (95% CI, 8.7-11.9 months) with placebo plus pembrolizumab plus chemotherapy (hazard ratio, 1.27; 95% CI, 1.02-1.57; P = .99); median overall survivalwas 18.9 months (95% CI, 15.2-23.8 months) vs 23.1 months (95% CI, 20.7-33.0 months) in each treatment group, respectively (hazard ratio, 1.33; 95% CI, 1.02-1.73; P = .98).

在数据截止时（中位随访时间为11.8个月），tiragolumab联合atezolizumab联合化疗的中位无进展生存期为8.3个月（95%置信区间，7.1-9.6个月），而安慰剂联合pembrolizumab联合化疗的中位无进展生存期为9.9个月（95%置信区间，8.7-11.9个月）（风险比，1.27；95%置信区间，1.02-1.57；P = .99）；每种治疗组的中位总生存期分别为18.9个月（95%置信区间，15.2-23.8个月）和23.1个月（95%置信区间，20.7-33.0个月）（风险比，1.33；95%置信区间，1.02-1.73；P = .98）。

Grade 3 to 4 adverse events occurred in 164 of 267 patients (61.4%) in the tiragolumab plus atezolizumab plus chemotherapy group and 165 of 272 patients (60.7%) in the placebo plus pembrolizumab plus chemotherapy group, with grade 5 AEs occurring in 27 of 267 patients (10.1%) and 16 of 272 patients (5.9%) in each group, respectively.

在 tiragolumab 加 atezolizumab 加化疗组的 267 名患者中，有 164 名（61.4%）发生了 3 到 4 级不良事件，在安慰剂加 pembrolizumab 加化疗组的 272 名患者中，有 165 名（60.7%）发生了 3 到 4 级不良事件，而每个组分别有 27 名（10.1%）和 16 名（5.9%）患者发生了 5 级不良事件。

conclusions_and_relevance

In the phase 3 SKYSCRAPER-06 randomized clinical trial, the primary end points were not met and the study has been terminated.

在第 3 期 SKYSCRAPER-06 随机临床试验中，主要终点未达到，研究已经终止。

trial_registration

ClinicalTrials.gov Identifier: NCT04619797.

临床试验注册号：NCT04619797。