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A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT in Children with Solid or CNS Tumours Expressing Epidermal Growth
Louise Evans1, Rick Walker2,3, Jennifer MacDiarmid4
1Michael Rice Centre for Haematology and Oncology, Women's and Children's Hospital, North Adelaide, SA, 5006, Australia.
Background:
Recurrent or refractory solid and central nervous system (CNS) tumours in paediatric patients have limited treatment options and carry a poor prognosis. The EnGeneIC Dream Vector (EDV) is a novel nanocell designed to deliver cytotoxic medication directly to the tumour. The epidermal growth factor receptor is expressed in several CNS and solid tumours and is the target for bispecific antibodies attached to the EDV.
Objective:
To assess the safety and tolerability of EGFR-Erbitux receptor EnGeneIC Dream Vector with mitoxantrone (EEDVsMit) in children with recurrent / refractory solid or CNS tumours expressing EGFR.
Patients And Methods:
Patients aged 2-21 years with relapsed or refractory CNS and solid tumours, or radiologically diagnosed diffuse intrinsic pontine glioma (DIPG), were treated in this phase I open-label study of single agent EEDVsMit. Thirty-seven patients' tumours were screened for EGFR expression. EEDVsMit was administered twice weekly in the first cycle and weekly thereafter. Standard dose escalation with a rolling 6 design was employed. Dosing commenced at 5 × 108 EEDVsMit per dose and escalated to 5 × 109 EEDVsMit per dose.
Results:
EGFR expression was detected in 12 (32%) of the paediatric tumours tested. Nine patients were enrolled and treated on the trial, including three patients with diffuse midline glioma. Overall, EEDVsMit was well tolerated, with no dose-limiting toxicities observed. The most common drug-related adverse events were grade 1-2 fever, nausea and vomiting, rash, lymphopaenia, and mildly deranged liver function tests. All patients had disease progression, including one patient who achieved a mixed response as the best response.
Conclusions:
EGFR-Erbitux receptor targeted EnGeneIC Dream Vector with mitoxantrone can be safely delivered in paediatric patients aged 2-21 years with solid or CNS tumours harbouring EGFR expression. The discovery of EGFR expression in a high proportion of paediatric gliomas means that EGFR may be useful as a target for other treatment strategies. Targeted therapeutic-loaded EDVs may be worth exploring further for their role in stimulating an anti-tumour immune response.
Gov Identifier:
NCT02687386.
Insights
This study found that EGFR-Erbitux receptor EnGeneIC Dream Vector with mitoxantrone (EDVsMit) is safe for children with recurrent solid or CNS tumors. While not curative, this targeted therapy shows promise for future pediatric cancer treatments.
Area of Science:
- Oncology
- Nanomedicine
- Pediatric Cancer Research
Background:
- Recurrent/refractory pediatric solid and CNS tumors have limited therapeutic options.
- EnGeneIC Dream Vector (EDV) is a nanocell designed for targeted cytotoxic drug delivery.
- Epidermal Growth Factor Receptor (EGFR) is a targetable protein on various tumors.
Purpose of the Study:
- To evaluate the safety and tolerability of EGFR-Erbitux receptor EnGeneIC Dream Vector with mitoxantrone (EDVsMit).
- To assess EDVsMit in pediatric patients (2-21 years) with recurrent/refractory solid or CNS tumors expressing EGFR.
Main Methods:
- Phase I, open-label study of single-agent EDVsMit in pediatric patients.
- Tumor EGFR expression screening in 37 patients; 9 patients enrolled and treated.
- Dose escalation from 5x10^8 to 5x10^9 EDVsMit, administered weekly after initial twice-weekly dosing.
Main Results:
- EGFR expression was found in 32% of tested pediatric tumors.
- EDVsMit was well-tolerated with no dose-limiting toxicities observed.
- Common adverse events included grade 1-2 fever, nausea, vomiting, rash, lymphopenia, and mild liver function abnormalities.
Conclusions:
- EGFR-targeted EDVsMit can be safely delivered to pediatric patients with EGFR-expressing solid or CNS tumors.
- EGFR is a potential therapeutic target in a significant proportion of pediatric gliomas.
- Further exploration of targeted EDVs for anti-tumor immune response stimulation is warranted.
