Abstract 2P
Background
CAN008 (Asunercept) is a recombinant glycosylated CD95-Fc fusion protein that disrupts the CD95/CD95L signaling pathway that promotes the growth and metastasis of tumor cells in glioblastoma multiforme (GBM). In 2016, a phase I/II open-label, dose-escalation trial of CAN008 as an add-on treatment to standard temozolomide/radiotherapy (TMZ/RT) treatment in newly-diagnosed GBM patients indicated that it was well-tolerated and showed promising efficacy. We now report long-term follow-up results from this study at our center.
Methods
Adults with newly diagnosed GBM were administered CAN008 (200 mg or 400 mg IV weekly) plus TMZ/RT for 6 weeks after tumor excision, followed by maintenance CAN008 plus TMZ until confirmed tumor recurrence or 24 months after surgery. Tumor samples were analyzed using next-generation whole exome sequencing.
Results
Between August 2016 and September 2017, 10 newly diagnosed GBM patients were enrolled and underwent surgical resection followed by standard TMZ/RT treatment. Of the 9 patients treated at Chang-Gung Memorial Hospital, 3 received low-dose (200 mg/week), and 6 received high-dose (400 mg/week) CAN008 treatment. 4 (high-dose group) of these 9 patients were alive at 5-year follow-up. The overall survival rate of the high-dose CAN008 group was 83% (95% CI 58.3-100) at 2 years, and it remained at 67% (37.9-100) at 3, 4, and 5 years, compared to an institutional database (N=218) that showed a declining rate of 34.3% (27.4-42.9), 19.5% (13.5-28.3), 16.1% (10.5-24.8), and 8.2% (3.9-17.1), respectively, at the same time points, and median progression-free survival was 17.95 months (3.7-NA), PFS was defined as the time from the date of the first diagnosis of GBM to the date of the first radiologically documented disease progression. DNA analysis revealed that a higher tumor mutation burden and a higher frequency of DNAH family gene mutations were associated with a favorable response to CAN008 treatment.
Conclusions
CAN008 400 mg IV weekly administered in conjunction with standard TMZ/RT treatment significantly improved the long-term outcomes of patients with newly-diagnosed GBM. Higher tumor mutation burden and a higher frequency of DNAH family gene mutations may be predictors of a favorable response to CAN008 treatment.
Clinical trial identification
NCT02853565.
Editorial acknowledgement
Legal entity responsible for the study
Hong-Chieh Tsai, Department of Neurosurgery, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan.
Funding
CANbridge Pharmaceuticals Inc., Shanghai, China.
Disclosure
G.F. Cox, F-M. Huang: Financial Interests, Personal, Full or part-time Employment: CANbridge Pharmaceuticals Inc. All other authors have declared no conflicts of interest.