====== NCT Neuro Master Match (N2M2) trial ======

The [[German National Center for Tumor Diseases]] (NCT) has developed a noncomparative screening [[trial]] called Neuro Master Match (N2M2) for first-line unmethylated [[glioblastoma classification]].

The NCT Neuro Master Match (N2M2) [[trial]] is an open-label, [[multicenter]], [[phase 1]]/IIa umbrella trial for patients with newly diagnosed [[Glioblastoma IDH wildtype]] without [[MGMT]] [[promoter]] [[hypermethylation]] to show safety, feasibility, and preliminary efficacy of [[treatment]] with targeted compounds in addition to standard [[radiotherapy]] based on [[molecular]] characterization. N2M2 is formally divided into a Discovery and a Treatment part. Discovery includes broad [[molecular]] neuropathological diagnostics to detect predefined [[biomarker]]s for targeted treatments. Molecular diagnostics and [[bioinformatics]] are performed within 4 weeks, allowing a timely initiation of postoperative treatment. Stratification for Treatment takes place in 5 subtrials, including [[alectinib]], [[idasanutlin]], [[palbociclib]], [[vismodegib]], and [[temsirolimus]] as targeted therapies, according to the best matching molecular alteration. Patients without matching alterations are randomized between subtrials without strong biomarkers using [[atezolizumab]] and [[asinercept]] (APG101) and the standard of care, TMZ. For the phase I parts, a [[Bayesian]] criterion is used for continuous monitoring of [[toxicity]]. In the [[phase 2]] trials, progression-free survival at 6 months is used as endpoint for [[efficacy]].

Molecular diagnostics and bioinformatic evaluation are performed within 4 weeks, allowing a timely initiation of postoperative treatment. Stratification for Treatment takes place in 5 subtrials, including alectinib, idasanutlin, palbociclib, vismodegib, and temsirolimus as targeted therapies, according to the best matching molecular alteration. Patients without matching alterations are randomized between subtrials without strong biomarkers using atezolizumab and asinercept (APG101) and the standard of care, TMZ. For the phase I parts, a Bayesian criterion is used for continuous monitoring of toxicity. In the phase II trials, progression-free survival at 6 months is used as endpoint for efficacy.

Molecularly informed trials may provide the basis for the development of predictive biomarkers and help to understand and select patient subgroups who will benefit
((Wick W, Dettmer S, Berberich A, Kessler T, Karapanagiotou-Schenkel I, Wick A, 
Winkler F, Pfaff E, Brors B, Debus J, Unterberg A, Bendszus M, Herold-Mende C,
Eisenmenger A, von Deimling A, Jones DTW, Pfister SM, Sahm F, Platten M. N2M2
(NOA-20) phase I/II trial of molecularly matched targeted therapies plus
radiotherapy in patients with newly diagnosed non-MGMT hypermethylated
glioblastoma. Neuro Oncol. 2019 Jan 1;21(1):95-105. doi: 10.1093/neuonc/noy161.
PubMed PMID: 30277538.
)).
----
The N2M2 study represents a significant advance in study design for evaluation of drugs in the early phase
II space for newly diagnosed GBM. It will be of great interest to the field to see how this design plays out in “real life,” and whether any of the substudies show evidence of efficacy in their target populations. Furthermore, the practical experience of using extensive multiplatform biomarker data in a large, prospective platform study will aid other platform efforts in the field, including adaptive
studies such as INSIGhT
((Tanguturi SK, Trippa L, Ramkissoon SH, et  al. Leveraging molecular
datasets for biomarker-based clinical trial design in glioblastoma. Neuro
Oncol. 2017;19(7):908–917.))
((Colman H. Toward more informative biomarker-based clinical trials in
glioblastoma. Neuro Oncol. 2017;19(7):880–881))
and GBM AGILE,
((Alexander BM, Ba S, Berger MS, et al; GBM AGILE Network. Adaptive
global innovative learning environment for glioblastoma: GBM AGILE.
Clin Cancer Res. 2018;24(4):737–743.))
which target the later phase II and phase III areas of drug evaluation for both newly diagnosed and recurrent GBM
((Colman H. A platform for efficient early evaluation of biomarker-associated
therapies in newly diagnosed IDH wild-type, MGMT unmethylated glioblastoma. Neuro
Oncol. 2019 Jan 1;21(1):6-7. doi: 10.1093/neuonc/noy190. PubMed PMID: 30590837.
)).

===== References =====