Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a N2M2 umbrella trial.

Here we report the results of the phase 1/2 umbrella trial NCT Neuro Master Match (N2M2), which evaluated targeted treatments in 228 patients with newly diagnosed glioblastoma without O6-methylguanine DNA-methyltransferase promoter hypermethylation.

我们报告了NCT Neuro Master Match (N2M2) 1/2期伞式试验的结果，该试验评估了228名新诊断的、没有O6-甲基鸟嘌呤DNA甲基转移酶启动子高甲基化的胶质母细胞瘤患者的靶向治疗。

Stratification for treatment was conducted by a trial-specific molecular tumor board across five subtrials, each evaluating a targeted therapy-alectinib, idasanutlin, palbociclib, vismodegib or temsirolimus-selected according to the best-matching molecular alteration.

治疗分层是通过特定于试验的分子肿瘤委员会进行的，该委员会评估了五项子试验，每项试验评估一种靶向治疗——阿来替尼、伊达沙替尼、帕博西利、维莫德吉布或特西莫司他，根据最佳匹配的分子改变进行选择。

Patients without matching alterations were randomized between subtrials without strong biomarkers using atezolizumab and asunercept, and the standard of care (SOC), temozolomide.

没有匹配改变的患者在没有强烈生物标志物的子试验之间随机分配使用阿替利珠单抗和阿苏纳塞普特，以及标准治疗（SOC），替莫唑胺。

All received radiotherapy.

所有患者均接受了放射治疗。

The primary endpoints were dose-limiting toxicities (phase 1) and progression-free survivalat 6 months (PFS-6; phase 2).

主要终点是剂量限制性毒性（第1阶段）和6个月无进展生存期（PFS-6；第2阶段）。

Secondary endpoints included safety and tolerability, as well as overall survival(OS).

次要终点包括安全性、耐受性以及总生存（OS）。

The subtrials for alectinib and vismodegib did not open as they did not have matching patients.

由于缺乏匹配的患者，阿来替尼和维莫德吉布的子试验未能启动。

The idasanutlin subtrial (n = 9) was terminated early at the discretion of the manufacturing company.

idasanutlin亚组试验(n=9)根据制造公司的决定提前终止。

The temsirolimus subtrial (n = 46) demonstrated a PFS-6 of 39.1% and median OS of 15.4 months in patients with activated mammalian target of rapamycin (mTOR) signaling compared to a PFS-6 at 18.5% in the SOC group (n = 54), meeting the primary endpoint.

temsirolimus亚组试验(n=46)显示，在mTOR信号通路激活的患者中，6个月无进展生存(PFS-6)为39.1%，中位总生存(OS)为15.4个月，与标准治疗组(n=54)的PFS-6为18.5%相比，达到了主要终点。

The atezolizumab (n = 42), asunercept (n = 26) and palbociclib (n = 41) subtrials did not meet the primary endpoint for efficacy.

Atezolizumab（n = 42），asunercept（n = 26）和palbociclib（n = 41）的子试验没有达到主要的疗效终点。

The safety signals of N2M2 match prior experiences with the drugs in quality and quantity; no relevant negative interaction with the parallel radiotherapy was noted.

N2M2的安全信号在质量和数量上与以往的药物经验相符；未发现与并行放疗有相关负面相互作用。

The results of the N2M2 trial support further investigation of temsirolimus in addition to radiotherapy in patients with newly diagnosed glioblastoma with activated mTOR signaling.

N2M2试验的结果支持在新诊断的mTOR信号通路激活的胶质母细胞瘤患者中，除了放疗外，进一步研究temsirolimus的作用。

ClinicalTrials.gov registration: NCT03158389 .

ClinicalTrials.gov注册信息：NCT03158389。