TY  - JOUR
AU  - Wick, Wolfgang
AU  - Lanz, Lisa-Marie
AU  - Wick, Antje
AU  - Harting, Inga
AU  - Dettmer, Susan
AU  - Suwala, Abigail K
AU  - Ketter, Ralf
AU  - Tabatabai, Ghazaleh
AU  - Seliger, Corinna
AU  - Glas, Martin
AU  - Burger, Michael C
AU  - Timmer, Marco
AU  - Ringel, Florian A
AU  - Mildenberger, Iris
AU  - Schulz-Schaeffer, Walter J
AU  - Winkler, Frank
AU  - König, Laila
AU  - Herold-Mende, Christel
AU  - Eisenmenger, Andreas
AU  - Pfister, Stefan
AU  - Renovanz, Mirjam
AU  - Bendszus, Martin
AU  - Sahm, Felix
AU  - Platten, Michael
AU  - Kessler, Tobias
TI  - Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a N2M2 umbrella trial.
JO  - Nature medicine
VL  - nn
SN  - 1078-8956
CY  - [New York, NY]
PB  - Springer Nature
M1  - DKFZ-2025-01857
SP  - nn
PY  - 2025
N1  - #EA:B320#LA:B320# / epub
AB  - Advances in molecular understanding and diagnostic precision of glioblastoma enable the identification of key genetic alterations in a timely manner and, in principle, allow treatments with targeted compounds based on molecular markers. 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. 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. Patients without matching alterations were randomized between subtrials without strong biomarkers using atezolizumab and asunercept, and the standard of care (SOC), temozolomide. All received radiotherapy. The primary endpoints were dose-limiting toxicities (phase 1) and progression-free survival at 6 months (PFS-6; phase 2). Secondary endpoints included safety and tolerability, as well as overall survival (OS). The subtrials for alectinib and vismodegib did not open as they did not have matching patients. The idasanutlin subtrial (n = 9) was terminated early at the discretion of the manufacturing company. The temsirolimus subtrial (n = 46) demonstrated a PFS-6 of 39.1
LB  - PUB:(DE-HGF)16
C6  - pmid:40913172
DO  - DOI:10.1038/s41591-025-03928-9
UR  - https://inrepo02.dkfz.de/record/304464
ER  -