CAN008 prolongs overall survival in patients with newly diagnosed GBM characterized by high tumor mutational burden

Ian Yi-Feng Chang, Hong-Chieh Tsai, Chia-Hua Chen, Hsiu-Chi Chen, Chia-Wen Huang, Gerald F Cox, Fang-Min Huang, You-Yu Lin, Ko-Ting Chen, Ya-Jui Lin, Kuo-Chen Wei

Research output: Contribution to journalJournal Article peer-review

Abstract

BACKGROUND: A previous phase 1 dose-escalation study in Taiwan indicated CAN008 (asunercept) with standard concurrent chemoradiotherapy (CCRT) improved progression-free survival (PFS) in newly diagnosed glioblastoma (GBM) patients. This study evaluates the efficacy of CAN008 in promoting overall survival (OS) and identifies genetic alterations associated with treatment responses.

METHODS: We compared OS of 5-year follow-ups from 9 evaluable CAN008 cohort patients (6 received high-dose and 3 received low-dose) to a historical Taiwanese GBM cohort with 164 newly diagnosed patients. CAN008 treatment response-associated genetic alterations were identified by whole-exome sequencing and comparing variant differences between response groups. Associations among patient survival, tumor mutational burden (TMB), and genetic alterations were analyzed using CAN008 cohort and TCGA-GBM dataset.

RESULTS: OS for high-dose CAN008 patients at 2 and 5 years was 83% and 67%, respectively, and 40.1% and 8.8% for the historical GBM cohort, respectively. Better OS was observed in the high-dose CAN008 cohort (without reaching the median survival) than the historical GBM cohort (median OS: 20 months; p=0.0103). Five high-dose CAN008 patients were divided into good and poor response groups based on their PFS. A higher variant count and TMB were observed in good response patients, whereas no significant association was observed between TMB and patient survival in the newly diagnosed TCGA-GBM dataset, suggesting TMB may modulate patient CAN008 response.

CONCLUSION: CAN008 combined with standard CCRT treatment prolonged the PFS and OS of newly diagnosed GBM patients compared to standard therapy alone. Higher treatment efficacy was associated with higher TMB.

Original languageEnglish
Pages (from-to)100660
JournalBiomedical Journal
DOIs
StateE-pub ahead of print - 21 09 2023

Bibliographical note

Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

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