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, multicenterphase 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 biomarkers 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 alectinibidasanutlinpalbociclibvismodegib, 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 2trials, 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 1).

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 2) 3) and GBM AGILE, 4) which target the later phase II and phase III areas of drug evaluation for both newly diagnosed and recurrent GBM 5).



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.

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

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.

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.

Eso Masterclass In Neuro-Oncology: Multidisciplinary Management Of Adult Brain Tumour

September 20 — September 22

Milan, Italy


The European School of Oncology was founded by Umberto Veronesi and Laudomia Del Drago in 1982, with the aim of contributing to the reduction of deaths from cancer due to late diagnosis and/or inadequate treatment. By improving the skills of all health professionals dealing with cancer patients, ESO helps shorten the time needed to transfer knowledge from research centres to daily practice, combining advanced technology with humanism in care.

ESO’s mission is reflected in its motto “Learning to Care”, which emphasises the importance of the learning process, and the goal of caring for the patient in a holistic sense, in contrast to focusing purely on treating the disease.

Due to its financial independence, ESO has the rare privilege of being able to set its own priorities. It therefore pays particular attention to developing the transfer of knowledge in areas that are least supported by industry, such as surgery and in rare pathologies (including childhood tumours), and in countries and regions with limited economic resources.

Fluorescence-Guided Neurosurgery: Neuro-oncology and Cerebrovascular Applications

The definitive textbook on state-of-the-art fluorescence-guided neurosurgery

Advances in fluorescence-guided surgery (FGS) have resulted in a paradigm shift in neurosurgical approaches to neuro-oncological and cerebrovascular pathologies. Edited by two of the foremost authorities on the topic, Fluorescence-Guided Neurosurgery: Neuro-oncology and Cerebrovascular Applications encompasses the depth and breadth of this groundbreaking, still nascent technology. The book reflects significant contributions made by world renowned neurosurgeons Constantinos Hadjipanayis, Walter Stummer, and esteemed contributors on the growing uses of 5-aminolevulinic acid (5-ALA) and other FGS agents.

The European Medicine Agency approved 5-ALA in 2007, heralding the birth of FGS globally. In 2017, the U.S. Food and Drug Administration approved 5-ALA (Gleolan) as an imaging agent to facilitate realtime detection and visualization of malignant tissue during glioma surgery. In the two decades since Dr. Stummer’s initial description of 5-ALA FGS in a human patient, major strides have been made in its practical applications, leading to improved resection outcomes. As FGS is increasingly incorporated into neurosurgical practice, it holds promise for future innovations. Generously-illustrated and enhanced with online videos, this textbook is the definitive resource on the subject.

Key Features

  • The improved efficacy of 5-ALA for resecting high- and low-grade gliomas, recurrences, meningiomas, brain metastases, spinal cord tumors, pediatric brain tumors, and other adult tumors
  • The future of fluorescence, including potentially powerful new fluorophores molecularly targeted specifically to tumors
  • The use of the fluorescent agent indocyanine green (ICG) for brain tumors, cerebral aneurysms, AVMs, and cerebral vascularization
  • Special topics such as fluorescein, illuminating tumor paint, confocal microscopy, Raman spectroscopy, and integrating FGS with intraoperative imaging and brain mapping

This single accessible reference presents the current state-of-the-art on this emerging, exciting surgical technology. As such, it is a must-have for neurosurgical residents, fellows, and practicing neurosurgeons.



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