biostudies-literatureUnknown7(1)Whittle JR<h4>Background</h4>This first-in-human study evaluated EGFRvIII × CD3 TCB, a novel T cell bispecific antibody, in patients with newly diagnosed EGFRvIII-positive glioblastoma.<h4>Methods</h4>Patients with newly diagnosed glioblastoma received escalating doses of EGFRvIII × CD3 TCB following chemoradiation. The primary objectives were to evaluate safety/tolerability and define the maximum tolerated dose (MTD); secondary objectives included pharmacokinetics (PK), immunogenicity, pharmacodynamics, and clinical activity.<h4>Results</h4>Thirty-six patients were enrolled, 32 with unmethylated and 4 with methylated MGMT promoter. EGFRvIII × CD3 TCB doses ranged from 0.004 to 10 mg Q3W, administered either on a flat or step-up dose schedule. One DLT occurred (grade 3 seizure). The MTD was not reacNeuro-oncology advancesvdaf160https://www.ebi.ac.uk/biostudies/studies/S-EPMC12365897biostudies-literatureFirst-in-human study of an EGFRvIII x CD3 T cell bispecific antibody in the treatment of newly diagnosed glioblastoma.PMC12365897Heichinger CRomagnoli BPrince FMellinghoff IKDey SFlinn NRoller AWick AMason WHenkel NRosenthal MWaldhauer IWolowski VGou JPCloughesy TSchneider MSmith LSchiff CReardon DAChong RAWhittle JRVieito MRodriguez-Ruiz MERohrberg KCastanon EVan Linde MHeil FDerks MfalseFirst-in-human study of an EGFRvIII x CD3 T cell bispecific antibody in the treatment of newly diagnosed glioblastoma.<h4>Background</h4>This first-in-human study evaluated EGFRvIII × CD3 TCB, a novel T cell bispecific antibody, in patients with newly diagnosed EGFRvIII-positive glioblastoma.<h4>Methods</h4>Patients with newly diagnosed glioblastoma received escalating doses of EGFRvIII × CD3 TCB following chemoradiation. The primary objectives were to evaluate safety/tolerability and define the maximum tolerated dose (MTD); secondary objectives included pharmacokinetics (PK), immunogenicity, pharmacodynamics, and clinical activity.<h4>Results</h4>Thirty-six patients were enrolled, 32 with unmethylated and 4 with methylated MGMT promoter. EGFRvIII × CD3 TCB doses ranged from 0.004 to 10 mg Q3W, administered either on a flat or step-up dose schedule. One DLT occurred (grade 3 seizure). The MTD was not reac2025-01-01T00:00:00Z2025 Jan-Dec2026-05-29T17:07:47.803Z2026-04-08T05:27:23.902ZS-EPMC123658974084264010.1093/noajnl/vdaf160