Mark M Souweidane, Evan D Bander, Pat Zanzonico, Anne S Reiner, Nicole Manino, Sofia Haque, Jorge A Carrasquillo, Serge K Lyashchenko, Sunitha B Thakur, Jason S Lewis, Maria Donzelli, Nai-Kong V Cheung, Steven M Larson, Kim Kramer, Neeta Pandit-Taskar, Ira J Dunkel
{"title":"使用对流增强递送（CED）放射免疫治疗124I-Omburtamab治疗弥漫性内在脑桥胶质瘤（DIPG）的一期剂量递增试验。","authors":"Mark M Souweidane, Evan D Bander, Pat Zanzonico, Anne S Reiner, Nicole Manino, Sofia Haque, Jorge A Carrasquillo, Serge K Lyashchenko, Sunitha B Thakur, Jason S Lewis, Maria Donzelli, Nai-Kong V Cheung, Steven M Larson, Kim Kramer, Neeta Pandit-Taskar, Ira J Dunkel","doi":"10.1093/neuonc/noaf039","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Median survival for patients with Diffuse Intrinsic Pontine Glioma (DIPG) is 8-12 months.</p><p><strong>Methods: </strong>A phase 1, open label, 3 + 3 dose-escalation trial delivered radiolabeled 124I-Omburtamab, targeting B7-H3, using MR-guided stereotactic convection-enhanced delivery (CED) into the brainstem of pediatric DIPG patients. CED was performed after completion of standard-of-care external-beam radiation therapy (EBRT). Fifty children were treated and evaluable. 124I-Omburtamab activity was escalated from 0.25 to 10.0 mCi (9.25-370 MBq) and volume escalated from 0.25 mL to 10.0 mL with serial PET/MRI post administration. Safety was the primary outcome. National Cancer Institute Common Terminology Criteria for Adverse Events were assessed for 30 days following CED of 124I-Omburtamab. Secondary outcomes included overall survival and lesion-to-whole-body absorbed dose ratio.</p><p><strong>Results: </strong>The maximum tolerated activity per study protocol was determined to be 6mCi (222 MBq). The overall mean (±SD) total absorbed dose in the lesion per unit injected activity was 35.2 ± 18 cGy/MBq with a high lesion-to-whole-body absorbed dose ratio averaging 816, across all activity levels. Eleven patients had treatment-related grade 3 CNS toxicities with no grade-4 or -5 CNS toxicities. Five dose-limiting toxicity events occurred. Median survival was 15.29 months from diagnosis (95% CI: 12.20-16.83 months). Survival rate estimates at 1, 2, and 3 years were 65.4% (CI 53.3-80.1%), 18.4% (CI: 10.2-33.2%), and 11.7% (CI: 5.3-25.7%), respectively.</p><p><strong>Conclusions: </strong>Administration of 124I-Omburtamab via CED is a safe treatment option for DIPG, with a maximum tolerated activity level identified. This study represents the first-in-human theranostic use of a 124I radiopharmaceutical, simultaneously, as an imaging and therapeutic agent.</p><p><strong>Trial registration: </strong>NCT01502917; https://clinicaltrials.gov/study/NCT01502917.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2117-2126"},"PeriodicalIF":13.4000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448826/pdf/","citationCount":"0","resultStr":"{\"title\":\"Phase 1 dose-escalation trial using convection-enhanced delivery of radio-immunotheranostic 124I-Omburtamab for diffuse intrinsic pontine glioma.\",\"authors\":\"Mark M Souweidane, Evan D Bander, Pat Zanzonico, Anne S Reiner, Nicole Manino, Sofia Haque, Jorge A Carrasquillo, Serge K Lyashchenko, Sunitha B Thakur, Jason S Lewis, Maria Donzelli, Nai-Kong V Cheung, Steven M Larson, Kim Kramer, Neeta Pandit-Taskar, Ira J Dunkel\",\"doi\":\"10.1093/neuonc/noaf039\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Median survival for patients with Diffuse Intrinsic Pontine Glioma (DIPG) is 8-12 months.</p><p><strong>Methods: </strong>A phase 1, open label, 3 + 3 dose-escalation trial delivered radiolabeled 124I-Omburtamab, targeting B7-H3, using MR-guided stereotactic convection-enhanced delivery (CED) into the brainstem of pediatric DIPG patients. CED was performed after completion of standard-of-care external-beam radiation therapy (EBRT). Fifty children were treated and evaluable. 124I-Omburtamab activity was escalated from 0.25 to 10.0 mCi (9.25-370 MBq) and volume escalated from 0.25 mL to 10.0 mL with serial PET/MRI post administration. Safety was the primary outcome. National Cancer Institute Common Terminology Criteria for Adverse Events were assessed for 30 days following CED of 124I-Omburtamab. Secondary outcomes included overall survival and lesion-to-whole-body absorbed dose ratio.</p><p><strong>Results: </strong>The maximum tolerated activity per study protocol was determined to be 6mCi (222 MBq). The overall mean (±SD) total absorbed dose in the lesion per unit injected activity was 35.2 ± 18 cGy/MBq with a high lesion-to-whole-body absorbed dose ratio averaging 816, across all activity levels. Eleven patients had treatment-related grade 3 CNS toxicities with no grade-4 or -5 CNS toxicities. Five dose-limiting toxicity events occurred. Median survival was 15.29 months from diagnosis (95% CI: 12.20-16.83 months). Survival rate estimates at 1, 2, and 3 years were 65.4% (CI 53.3-80.1%), 18.4% (CI: 10.2-33.2%), and 11.7% (CI: 5.3-25.7%), respectively.</p><p><strong>Conclusions: </strong>Administration of 124I-Omburtamab via CED is a safe treatment option for DIPG, with a maximum tolerated activity level identified. This study represents the first-in-human theranostic use of a 124I radiopharmaceutical, simultaneously, as an imaging and therapeutic agent.</p><p><strong>Trial registration: </strong>NCT01502917; https://clinicaltrials.gov/study/NCT01502917.</p>\",\"PeriodicalId\":19377,\"journal\":{\"name\":\"Neuro-oncology\",\"volume\":\" \",\"pages\":\"2117-2126\"},\"PeriodicalIF\":13.4000,\"publicationDate\":\"2025-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448826/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuro-oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/neuonc/noaf039\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro-oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/neuonc/noaf039","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Phase 1 dose-escalation trial using convection-enhanced delivery of radio-immunotheranostic 124I-Omburtamab for diffuse intrinsic pontine glioma.
Background: Median survival for patients with Diffuse Intrinsic Pontine Glioma (DIPG) is 8-12 months.
Methods: A phase 1, open label, 3 + 3 dose-escalation trial delivered radiolabeled 124I-Omburtamab, targeting B7-H3, using MR-guided stereotactic convection-enhanced delivery (CED) into the brainstem of pediatric DIPG patients. CED was performed after completion of standard-of-care external-beam radiation therapy (EBRT). Fifty children were treated and evaluable. 124I-Omburtamab activity was escalated from 0.25 to 10.0 mCi (9.25-370 MBq) and volume escalated from 0.25 mL to 10.0 mL with serial PET/MRI post administration. Safety was the primary outcome. National Cancer Institute Common Terminology Criteria for Adverse Events were assessed for 30 days following CED of 124I-Omburtamab. Secondary outcomes included overall survival and lesion-to-whole-body absorbed dose ratio.
Results: The maximum tolerated activity per study protocol was determined to be 6mCi (222 MBq). The overall mean (±SD) total absorbed dose in the lesion per unit injected activity was 35.2 ± 18 cGy/MBq with a high lesion-to-whole-body absorbed dose ratio averaging 816, across all activity levels. Eleven patients had treatment-related grade 3 CNS toxicities with no grade-4 or -5 CNS toxicities. Five dose-limiting toxicity events occurred. Median survival was 15.29 months from diagnosis (95% CI: 12.20-16.83 months). Survival rate estimates at 1, 2, and 3 years were 65.4% (CI 53.3-80.1%), 18.4% (CI: 10.2-33.2%), and 11.7% (CI: 5.3-25.7%), respectively.
Conclusions: Administration of 124I-Omburtamab via CED is a safe treatment option for DIPG, with a maximum tolerated activity level identified. This study represents the first-in-human theranostic use of a 124I radiopharmaceutical, simultaneously, as an imaging and therapeutic agent.
期刊介绍：
Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field.
The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.
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