Pelareorep and granulocyte-macrophage colony-stimulating factor (GM-CSF) with standard chemoradiotherapy/adjuvant temozolomide for glioblastoma multiforme (GBM) patients: reoglio phase I trial results
Kendall, J. Chalmers, A. McBain, Catherine A Melcher, A. Samson, A. Phillip, R. Brown, S. Short, S.
Kendall, J.
Chalmers, A.
McBain, Catherine A
Melcher, A.
Samson, A.
Phillip, R.
Brown, S.
Short, S.
Citations
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Abstract
BACKGROUND: Oncolytic viruses represent a novel treatment approach
in GBM through oncolytic targeting as well as local immune activation.
We designed a phase Ib, open-label study of intravenous reovirus
(pelareorep) with GM-CSF alongside standard chemoradiotherapy to assess
safety and tolerability. METHODS: 15 patients with newly diagnosed GBM
were treated with GM-CSF 50mg subcutaneously (days 1–3) and pelareorep
(days 4–5) in weeks 1 and 4 of chemoradiotherapy, and week 1 of adjuvant
temozolomide course: 7 patients received 1x1010TCID50 (dose level 1); 8 received 3x1010TCID50 (dose level 2). The primary objective was to
determine the maximum tolerated dose of pelareorep and GM-CSF with
standard chemoradiotherapy. Secondary objectives were to gain preliminary
assessment of the activity of the combination and assess treatment compliance.
RESULTS: 1 dose limiting toxicity (DLT) and 20 SAEs were experienced
overall; median number of SAEs per patient was 2. Commonest SAEs
were nervous system disorders, predominantly seizures. SARs included fever/
flu-like episodes (n=5), fall (n=1) and headache (n=1). Two SUSARs occurred
in dose level 2, classed as vascular disorders manifesting as hypotension episodes
– one was a DLT. Suspected relationship of SARs: pelareorep (n=6);
temozolomide (n=1); radiotherapy (n=1); all study drugs (n=1). 87% of patients
(n=13) completed chemoradiotherapy without unplanned delays. Adjuvant
treatment was delayed in 21% of cycles overall, with the majority due
to inadequate haematology/biochemistry values (44% of delays). Pelareorep
was omitted in 4 instances in 4 patients during chemoradiotherapy and
omitted in 4 instances in 3 patients during adjuvant treatment. CONCLUSION:
We present the first clinical data using intravenous pelareorep with
GM-CSF alongside standard chemoradiotherapy in patients with GBM, suggesting
that the combination is tolerable. Further analysis is underway and
efficacy results will be ready for presentation at the conference.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Kendall J, Chalmers A, McBain C, Melcher A, Samson A, Phillip R, et al. Ctim-14. Pelareorep and Granulocyte-Macrophage Colony-Stimulating Factor (Gm-Csf) with Standard Chemoradiotherapy/Adjuvant Temozolomide for Glioblastoma Multiforme (Gbm) Patients: Reoglio Phase I Trial Results. Neuro-Oncology. 2020;22(Supplement_2):ii35-ii6.