Avelumab in newly diagnosed glioblastoma

Francois H Jacques; Garth Nicholas; Ian A J Lorimer; Victorine Sikati Foko; Jasmine Prevost; Nathalie Dumais; Katy Milne; Brad H Nelson; John Woulfe; Gerard Jansen; B Erik Apedaile

doi:10.1093/noajnl/vdab118

Avelumab in newly diagnosed glioblastoma

Neurooncol Adv. 2021 Aug 25;3(1):vdab118. doi: 10.1093/noajnl/vdab118. eCollection 2021 Jan-Dec.

Authors

Francois H Jacques¹, Garth Nicholas^{2

3}, Ian A J Lorimer^{2

4

3}, Victorine Sikati Foko¹, Jasmine Prevost¹, Nathalie Dumais¹, Katy Milne⁵, Brad H Nelson^{5

6

7}, John Woulfe⁸, Gerard Jansen⁸, B Erik Apedaile¹

Affiliations

¹ Clinique Neuro-Outaouais, Gatineau, Quebec, Canada.
² Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
³ Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁴ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
⁵ Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.
⁶ Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
⁷ Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia,Canada.
⁸ Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Abstract

Background: Glioblastoma (GBM) is known to use both local and systemic immunosuppressive strategies. One such strategy is the expression of the immune checkpoint protein programmed cell death ligand-1 (PD-L1) by both tumor cells and tumor-associated immune cells. Recent phase III trials using IgG4 antibodies targeting PD-1, the ligand for PD-L1, failed to show any benefit. Avelumab is an IgG1 monoclonal antibody targeting PD-L1. In contrast to the previously tested immune checkpoint inhibitors, it can directly bind tumor cells and immune cells expressing PD-L1 and can induce antibody-dependent cellular cytotoxicity.

Methods: We conducted a single center, open label, phase II study where avelumab 10 mg/kg IV Q2W was added concurrently to the first monthly temozolomide cycle in patients with newly diagnosed GBM. Immunohistochemical analyses were performed on surgery samples. The primary objective was safety. Secondary objectives were efficacy outcomes according to the immunotherapy Response Assessment in Neuro Oncology criteria, progression free survival (PFS), and overall survival (OS). Exploratory objectives aimed at determining prognostic biomarkers.

Results: Thirty patients were started on therapy and two were lost to follow-up. Median follow-up time (reverse Kaplan-Meier) was 41.7 months (IQR: 28.3-43.4). Three (10.0%) patients had a related or possibly related treatment emergent adverse event that lead to transient or permanent discontinuation of avelumab. Eight (26.7%) patients had one or more immune-related adverse events, and 8 (26.7%) patients had an infusion-related reaction. The overall response rate was 23.3%, median PFS was 9.7 months, and the median OS was 15.3 months. No pretreatment biomarkers showed any predictive value.

Conclusions: The addition of avelumab to standard therapy in patients with GBM was not associated with any new safety signal. There was no apparent improvement in OS.

Trial registration: NCT03047473 Registered February 9, 2017.

Keywords: PD-L1; avelumab; glioblastoma; immune checkpoint inhibitor; phase II.

Associated data

ClinicalTrials.gov/NCT03047473