By Lynda Williams, medwireNews Reporter
medwireNews: Intracerebral recombinant polio–rhinovirus immunotherapy is feasible in children and young people with heavily pretreated, high-grade malignant glioma, suggest phase 1b trial findings published in The Lancet Child & Adolescent Health.
“Convection enhanced delivery of lerapolturev is safe enough in the treatment of recurrent paediatric high-grade glioma to proceed to the next phase of trial”, say David Ashley (Duke University, Durham, North Carolina, USA) and co-authors.
The team explains that CD155, the receptor targeted by the genetically engineered polio–rhinovirus chimera lerapolturev, is “ubiquitously expressed in malignant paediatric brain tumours” and lerapolturev has been shown in mice to induce inflammation in glioma leading to an anti-tumour CD8+ T-cell response. Furthermore, a phase 1 trial of the treatment in adults with recurrent glioblastoma resulted in 16% of patients surviving for at least 36 months.
The current study included five boys and three girls aged a median of 16.5 years (range 11.0–18.0 years). Six patients were White and two were Black or African American.
The patients were diagnosed a median of 21.07 months earlier with WHO grade 3 or 4 glioma, namely IDH-wild-type glioblastoma (n=4), H3G34-mutated diffuse hemispheric glioma (n=3) or IDH-mutant astrocytoma (n=1). They had received a median 3.5 chemotherapy regimens.
A single 3 mL lerapolturev infusate, containing a 5 x 107 median tissue culture infectious dose, was delivered over approximately 6.5 hours via a catheter tunnelled to at least 5 cm beneath the scalp of each child, the researchers say.
The primary endpoint of unacceptable toxicity in the following 14 days did not occur and none of the patients experienced grade 4 or more severe adverse events lasting over 2 weeks.
There were 26 treatment-related adverse events in six patients including two cases of grade 3 headache and one grade 3 seizure. Four patients were given low-dose bevacizumab for peritumoural inflammation or oedema diagnosed by magnetic resonance imaging.
All three deaths that occurred within 30 days of the initial study period were related to disease progression.
Ashley et al note that the median overall survival of 4.1 months is “considerably longer than shown in historical data” but emphasize that “it is unclear if this improvement was due to treatment on this trial or treatment before enrolment and after patients finished the initial study period.”
They say that one patient was alive after more than 22 months of follow-up but note that this participant had favourable disease characteristics, such as a “relatively small” grade 3 glioma with an IDH1 mutation, and had also received “multiple treatments” after the polio–rhinovirus immunotherapy.
The team concludes that “lerapolturev via convection enhanced delivery for the treatment of recurrent paediatric high-grade glioma met the predefined clinical endpoints, providing rationale to proceed with further clinical trials.”
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Lancet Child Adolesc Health 2023; doi:10.1016/S2352-4642(23)00031-7