Department of Medicine, Duke University, Durham, North Carolina, USA
Division of Pneumo-Oncology, Hôpital Sainte Musse, Toulon, Provence-Alpes-Côte d'Azur, France.
J Immunother Cancer. 2023 Feb;11(2). doi: 10.1136/jitc-2022-006127.
CheckMate 817, a phase 3B study, evaluated flat-dose nivolumab plus weight-based ipilimumab in patients with metastatic non-small cell lung cancer (NSCLC). Here, in this research, we report on first-line treatment in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (cohort A) and special populations (cohort A1: ECOG PS 2; or ECOG PS 0-1 with untreated brain metastases, renal impairment, hepatic impairment, or controlled HIV infection).
Cohorts A and A1 received nivolumab 240 mg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary endpoint was the incidence of grade 3-4 and grade 5 immune-mediated adverse events (IMAEs; adverse events (AEs) deemed potentially immune-related, occurring <100 days of last dose, and treated with immune-modulating medication (except endocrine events)) and treatment-related select AEs (treatment-related AEs with potential immunological etiology requiring frequent monitoring/intervention, reported between first dose and 30 days after the last dose) in cohort A; efficacy endpoints were secondary/exploratory. In cohort A1, safety/efficacy assessment was exploratory.
The most common grade 3-4 IMAEs were pneumonitis (5.1%), diarrhea/colitis (4.9%), and hepatitis (4.6%) in cohort A (N=391) and diarrhea/colitis (3.5%), hepatitis (3.5%), and rash (3.0%) in cohort A1 (N=198). The most common grade 3-4 treatment-related select AEs were hepatic (5.9%), gastrointestinal (4.9%), and pulmonary (4.6%) events in cohort A and gastrointestinal (4.0%), skin (3.5%), and endocrine (3.0%) events in cohort A1. No grade 5 IMAEs or treatment-related select AEs occurred. Treatment-related deaths occurred in 4 (1.0%) and 3 (1.5%) patients in cohorts A and A1, respectively. Three-year overall survival (OS) rates were 33.7% and 20.5%, respectively.
Flat-dose nivolumab plus weight-based ipilimumab was associated with manageable safety and durable efficacy in cohort A, consistent with data from phase 3 metastatic NSCLC studies. Special populations of cohort A1 including patients with ECOG PS 2 or ECOG PS 0-1 with untreated brain metastases had manageable treatment-related toxicity and clinically meaningful 3-year OS rate.
NCT02869789.
CheckMate 817 是一项 3B 期研究，评估了固定剂量纳武利尤单抗联合基于体重的伊匹单抗在转移性非小细胞肺癌（NSCLC）患者中的疗效。在此，我们报告了体能状态（PS）0-1 （队列 A）和特殊人群（队列 A1：PS 2；或 PS 0-1 且未经治疗的脑转移、肾功能不全、肝功能不全或控制良好的 HIV 感染）患者的一线治疗结果。
队列 A 和 A1 患者接受纳武利尤单抗 240mg 每 2 周，伊匹单抗 1mg/kg 每 6 周。主要终点是 3-4 级和 5 级免疫介导的不良事件（IMAE；被认为具有潜在免疫相关性的不良事件，发生在末次用药后 100 天内，并用免疫调节药物治疗（内分泌事件除外））和治疗相关的选择不良事件（具有潜在免疫病因学的治疗相关不良事件，需要频繁监测/干预，报告时间为首次用药至末次用药后 30 天）在队列 A 中；疗效终点为次要/探索性终点。在队列 A1 中，安全性/疗效评估为探索性的。
最常见的 3-4 级 IMAE 是肺炎（5.1%）、腹泻/结肠炎（4.9%）和肝炎（4.6%）在队列 A（n=391）和腹泻/结肠炎（3.5%）、肝炎（3.5%）和皮疹（3.0%）在队列 A1（n=198）。最常见的 3-4 级治疗相关的选择不良事件是肝脏（5.9%）、胃肠道（4.9%）和肺部（4.6%）事件在队列 A 中，胃肠道（4.0%）、皮肤（3.5%）和内分泌（3.0%）事件在队列 A1 中。没有发生 5 级 IMAE 或治疗相关的选择不良事件。在队列 A 和 A1 中，分别有 4 例（1.0%）和 3 例（1.5%）患者发生治疗相关死亡。3 年总生存率（OS）分别为 33.7%和 20.5%。
固定剂量纳武利尤单抗联合基于体重的伊匹单抗在队列 A 中具有可管理的安全性和持久的疗效，与转移性 NSCLC 研究的 3 期数据一致。队列 A1 中的特殊人群包括 PS 2 或 PS 0-1 且未经治疗的脑转移患者，具有可管理的治疗相关毒性和有临床意义的 3 年 OS 率。
NCT02869789。
