未甲基化新诊断胶质母细胞瘤的双重免疫检查点阻断：NRG肿瘤学BN007，一项随机II/III期临床试验。
Dual Immune Check Point Blockade in -Unmethylated Newly Diagnosed Glioblastoma: NRG Oncology BN007, a Randomized Phase II/III Clinical Trial.
作者信息
Lassman Andrew B, Polley Mei-Yin C, Iwamoto Fabio M, Sloan Andrew E, Wang Tony J C, Aldape Kenneth D, Wefel Jeffrey S, Gondi Vinai, Gutierrez Alonso N, Manasawala Mohammed H, Gilbert Mark R, Sulman Erik P, Wolchok Jedd D, Green Richard M, Neil Elizabeth C, Lukas Rimas V, Goldlust Samuel A, Snuderl Matija, Galbraith Kristyn, Dignam James J, Won Minhee, Mehta Minesh P
机构信息
Division of Neuro-Oncology, Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY.
Herbert Irving Comprehensive Cancer Center, New York, NY.
出版信息
J Clin Oncol. 2025 Aug 8:JCO2500618. doi: 10.1200/JCO-25-00618.
PURPOSE
New therapies for glioblastoma are needed, especially -unmethylated (u) disease. NRG Oncology BN002 (phase I) demonstrated safety and suggested efficacy of ipilimumab (ipi) with nivolumab (nivo) in newly diagnosed glioblastoma, leading to this phase II/III trial.
METHODS
Adults with newly diagnosed u glioblastoma and Karnofsky performance status (KPS) ≥70 were randomly assigned to radiotherapy with either immunotherapy (ipi and nivo) or temozolomide (TMZ), stratified by recursive partitioning analysis (RPA) class and intention to use tumor treating fields. With 95% power to detect a hazard ratio (HR) ≤0.58 for progression-free survival (PFS) at a one-sided significance level () of .15, superior PFS with immunotherapy in phase II would lead to phase III overall survival (OS) testing. Corticosteroids were disallowed when starting immunotherapy. Diagnosis, biomarkers, and PFS were centrally assessed.
RESULTS
One hundred fifty-nine participants were randomly assigned (79 immunotherapy and 80 TMZ). Arms were well balanced for age (median 60 years, range, 28-79), sex (male n = 105, 66%), KPS (90-100 n = 97, 61%), resection extent (gross total, n = 103, 65%), and RPA class (III, n = 16, 10%; IV, n = 116, 73%; V, n = 27, 17%). A preplanned analysis of phase II data conducted after 100 centrally determined PFS events showed no significant PFS improvement for ipi and nivo versus TMZ (median 7.7 months 8.5 months, HR, 1.47 [70% CI, 1.19 to 1.83]; one-sided = .96 [95% CI, 0.98 to 2.2]). OS is immature (>50% alive) but with no observed difference between arms (median approximately 13 months each, HR, 0.95 [95% CI, 0.61 to 1.49]; = .36).
CONCLUSION
Ipi and nivo did not improve PFS among patients with newly diagnosed u glioblastoma versus TMZ. Accrual closed permanently; the trial will not proceed to phase III. No new safety signals were identified. Molecular correlative analyses and survival follow-up are ongoing.
目的
需要针对胶质母细胞瘤开发新的治疗方法，尤其是未甲基化（u）疾病。NRG肿瘤学BN002（I期）试验证明了伊匹单抗（ipi）联合纳武单抗（nivo）在新诊断的胶质母细胞瘤中的安全性，并显示出一定疗效，从而开展了这项II/III期试验。
方法
将新诊断为u型胶质母细胞瘤且卡诺夫斯基性能状态（KPS）≥70的成年人随机分配接受免疫疗法（ipi和nivo）或替莫唑胺（TMZ）联合放射治疗，根据递归分区分析（RPA）类别和是否打算使用肿瘤治疗电场进行分层。在单侧显著性水平为0.15的情况下，若有95%的把握度检测到无进展生存期（PFS）的风险比（HR）≤0.58，则II期免疫疗法组PFS的优越性将导致进行III期总生存期（OS）测试。开始免疫治疗时不允许使用皮质类固醇。对诊断、生物标志物和PFS进行集中评估。
结果
159名参与者被随机分配（79名接受免疫疗法，80名接受TMZ）。两组在年龄（中位数60岁，范围28 - 79岁）、性别（男性n = 105，66%）、KPS（90 - 100分的n = 97，61%）、切除范围（全切，n = 103，‘65%）和RPA类别（III类，n = 16，10%；IV类，n = 116，73%；V类，n = 27，17%）方面平衡良好。在100例由中心确定的PFS事件后对II期数据进行的预先计划分析显示，ipi和nivo组与TMZ组相比，PFS无显著改善（中位数分别为7.7个月和8.5个月，HR为1.47 [70% CI，1.19至1.83]；单侧P = 0.96 [95% CI，0.98至2.2]）。OS数据不成熟（超过50%存活），但两组之间未观察到差异（中位数均约为13个月，HR为0.95 [95% CI，0.61至1.49]；P = 0.36）。
结论
对于新诊断的u型胶质母细胞瘤患者，ipi和nivo与TMZ相比并未改善PFS。入组已永久结束；该试验不会进入III期。未发现新的安全信号。分子相关性分析和生存随访正在进行中。
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