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

doi:10.1016/j.bj.2023.100660

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

Biomed J. 2023 Sep 21:100660. doi: 10.1016/j.bj.2023.100660. Online ahead of print.

Authors

Affiliations

¹ Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
² School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
³ Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
⁴ School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Neurosurgery, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan.
⁵ CANbridge Pharmaceuticals, Burlington, MA, USA.
⁶ CANbridge Pharmaceuticals Inc., Shanghai, China.
⁷ Genome and Systems Biology Degree Program, Academia Sinica and National Taiwan University, Taipei.
⁸ School of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
⁹ School of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; Department of Neurosurgery, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan. Electronic address: kuochenwei@cgmh.org.tw.

PMID: 37741340
DOI: 10.1016/j.bj.2023.100660

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.

Keywords: Asunercept; CAN008; GBM; immunotherapy; tumor mutational burden.