背景：在 3 期随机 CheckMate 9LA 试验（NCT03215706）中，一线 NIVO + IPI 联合2 周期化疗与单药化疗 4 周期相比，显著改延长了总生存期 （OS）， 无进展生存期 （PFS）和客观应答率 （ORR）。无论 PD-L1 表达水平和组织学分型如何，我们都观察到临床疗效。我们将在此汇报至少 2 年的跟踪随访数据。

Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study.

方法：我们将 IV 期或复发 NSCLC、ECOG 评分≤1 分 和已知无明确 EGFR/ALK 突变的成人患者（pts）按 PD-L1（< 1% 与 ≥1%），性别，和组织学表型 （鳞癌 VS 非鳞癌）分层，并被 1：1 随机分组到 NIVO 360 mg Q3W + IPI 1 mg / kg Q6W + 化疗 （2 周期; n = 361） 或单药化疗 （4 周期; n = 358）。在化疗组中非鳞 NSCLC 的 pts 可以接受培美曲塞维持。主要终点是 OS。次要终点包括通过独立中心盲审的 PFS 和 ORR，以及 PD-L1 不同等级的疗效。此研究的安全性是得以保证的。

Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory.

结果：OS 至少随访 24.4 个月（数据库于 2021 年 2 月 18 日锁定），经 NIVO + IPI + chemo 治疗的 pts 与单药化疗相比得到了 OS 获益，中位 OS 分别为 15.8 个月与 11.0 个月（HR， 0.72 [95% CI， 0.61–0.86]）;2 年 OS 率分别为 38%和 26%。经 NIVO + IPI + chemo 治疗与单药化疗的中位 PFS 分别为 6.7 个月与 5.3 个月 （HR，0.67 [95% CI，0.56-0.79]）；分别有 8%和 37%的有疾病进展的患者接受了后续免疫治疗。NIVO+IPI+chemo ORR 38% VS 单药化疗 ORR 25%。在所有随机分组的 pts 和大多数子分组都观察到了类似于 NIVO+ IPI + chemo VS 单药化疗的临床获益，包括不同的 PD-L1 表达水平或组织学分型。与治疗相关的任何等级和 3-4 级不良事件在 NIVO + IPI + chemo 组分别为 92% 和 48% VS 化疗组为 88% 和 38%。

Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively.

结论：在晚期 Nsclc 的 pts 治疗中，至少２年的随访、一线 NIVO + IPI + chemo 方案具有持久生存和临床获益；未发现新的安全信号。

Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified.