Puma Biotechnology, Inc. announced that investigators presented results from the neratinib arm of the Phase II Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT Trial) at the 2021 Society for Neuro-Oncology Annual Meeting. The INSIGhT trial is a multisite investigator-initiated Phase II screening adaptive platform trial where patients with newly diagnosed unmethylated glioblastoma who are IDH R132H mutation negative and with genomic data available for biomarker grouping are eligible. All patients receive radiation therapy and temozolomide and then patients are randomized to receive either adjuvant temozolomide or adjuvant treatment with an experimental agent (neratinib). At the initiation of INSIGhT, three experimental arms, each with a proposed genomic biomarker, are tested simultaneously. Initial randomization is equal across arms. As the trial progresses, randomization probabilities adapt on the basis of accumulating results using Bayesian estimation of the biomarker-specific probability of treatment impact on progression-free survival. Treatment arms were allowed to drop because of low probability of treatment impact on overall survival. The primary endpoint of INSIGhT is overall survival (OS). Progression-free survival (PFS) analysis is used to influence randomization. For the neratinib arm of the trial, patients received 240 mg of neratinib daily as a single agent with mandatory loperamide prophylaxis. For the neratinib arm of the trial, there were 149 patients in the intent-to-treat population, including 81 patients treated with neratinib and 68 patients in the control arm. For the intent-to-treat population, PFS was not significantly longer (HR 0.75; p=0.12, log rank test) with neratinib (median 6.0 months) versus the control arm (median 4.7 months) and there was no significant improvement in OS (HR 1.01; p=0.75) between neratinib (median 13.8 months) vs. the control arm (median 14.7 months). For patients with activation of the EGFR pathway, defined as patients with either EGFR amplification or mutation, PFS was significantly longer (HR 0.58; p=0.04, log rank test) with neratinib (median 6.3 months) vs. the control arm (median 4.6 months); however, there was no significant improvement in overall survival (HR 0.97; p= 0.94) between neratinib (median 14.4 months) vs. the control arm (median 15.3 months). Neratinib was generally well tolerated in the trial and toxicities for neratinib were similar to that previously described. For the 81 patients treated with neratinib, there were 6 cases (7.4%) of grade 3 diarrhea and no cases of grade 4 diarrhea. No new toxicity signals were identified in the trial.