Louise Evans, Rick Walker, Jennifer MacDiarmid, Himanshu Brahmbhatt, Antoinette Anazodo, Geoffrey McCowage, Andrew J Gifford, Maria Kavallaris, Toby Trahair, David S Ziegler
{"title":"表达表皮生长因子受体的实体瘤或中枢神经系统肿瘤患儿静脉注射表皮生长因子受体-ErbituxEDVsMIT 的 1 期研究。","authors":"Louise Evans, Rick Walker, Jennifer MacDiarmid, Himanshu Brahmbhatt, Antoinette Anazodo, Geoffrey McCowage, Andrew J Gifford, Maria Kavallaris, Toby Trahair, David S Ziegler","doi":"10.1007/s11523-024-01051-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To assess the safety and tolerability of EGFR-Erbitux receptor EnGeneIC Dream Vector with mitoxantrone (<sup>E</sup>EDVs<sub>Mit</sub>) in children with recurrent / refractory solid or CNS tumours expressing EGFR.</p><p><strong>Patients and methods: </strong>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 <sup>E</sup>EDVs<sub>Mit</sub>. Thirty-seven patients' tumours were screened for EGFR expression. <sup>E</sup>EDVs<sub>Mit</sub> 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 × 10<sup>8 E</sup>EDVs<sub>Mit</sub> per dose and escalated to 5 × 10<sup>9 E</sup>EDVs<sub>Mit</sub> per dose.</p><p><strong>Results: </strong>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, <sup>E</sup>EDVs<sub>Mit</sub> 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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT02687386.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"333-342"},"PeriodicalIF":4.4000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111512/pdf/","citationCount":"0","resultStr":"{\"title\":\"A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT in Children with Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor.\",\"authors\":\"Louise Evans, Rick Walker, Jennifer MacDiarmid, Himanshu Brahmbhatt, Antoinette Anazodo, Geoffrey McCowage, Andrew J Gifford, Maria Kavallaris, Toby Trahair, David S Ziegler\",\"doi\":\"10.1007/s11523-024-01051-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To assess the safety and tolerability of EGFR-Erbitux receptor EnGeneIC Dream Vector with mitoxantrone (<sup>E</sup>EDVs<sub>Mit</sub>) in children with recurrent / refractory solid or CNS tumours expressing EGFR.</p><p><strong>Patients and methods: </strong>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 <sup>E</sup>EDVs<sub>Mit</sub>. Thirty-seven patients' tumours were screened for EGFR expression. <sup>E</sup>EDVs<sub>Mit</sub> 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 × 10<sup>8 E</sup>EDVs<sub>Mit</sub> per dose and escalated to 5 × 10<sup>9 E</sup>EDVs<sub>Mit</sub> per dose.</p><p><strong>Results: </strong>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, <sup>E</sup>EDVs<sub>Mit</sub> 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.</p><p><strong>Conclusions: </strong>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. 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A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT in Children with Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor.
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.
期刊介绍：
Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes:
Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches.
Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways.
Current Opinion articles that place interesting areas in perspective.
Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations.
Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement.
Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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