Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial.

التفاصيل البيبلوغرافية
العنوان:	Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial.
المؤلفون:	Johnson TS; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.; Department of Pediatrics, Augusta University, Augusta, Georgia, USA., MacDonald TJ; Aflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA., Pacholczyk R; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA., Aguilera D; Aflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA., Al-Basheer A; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.; Department of Radiation Oncology, Augusta University, Augusta, Georgia, USA., Bajaj M; Department of Radiology, Augusta University, Augusta, Georgia, USA., Bandopadhayay P, Berrong Z; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA., Bouffet E; Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada., Castellino RC; Aflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA., Dorris K; Department of Pediatrics, Children's Hospital Colorado, Aurora, Colorado, USA., Eaton BR; Department of Radiation Oncology and Winship Cancer Institute of Emory University, Atlanta, Georgia, USA., Esiashvili N; Department of Radiation Oncology and Winship Cancer Institute of Emory University, Atlanta, Georgia, USA., Fangusaro JR; Aflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA., Foreman N; Department of Pediatrics, Children's Hospital Colorado, Aurora, Colorado, USA., Fridlyand D; Department of Pediatrics, Augusta University, Augusta, Georgia, USA., Giller C; Department of Neurosurgery, Augusta University, Augusta, Georgia, USA., Heger IM; Department of Neurosurgery, Augusta University, Augusta, Georgia, USA., Huang C; Department of Pediatrics, Emory University, Atlanta, Georgia, USA.; Department of Biomedical Informatics, Emory University, Atlanta, Georgia, USA., Kadom N; Department of Radiology and Winship Cancer Institute of Emory University, Atlanta, Georgia, USA., Kennedy EP; Lumos Pharma, Inc. (formerly NewLink Genetics Corporation), Austin, Texas, USA., Manoharan N; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA., Martin W; Department of Radiation Oncology, Augusta University, Augusta, Georgia, USA., McDonough C; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.; Department of Pediatrics, Augusta University, Augusta, Georgia, USA., Parker RS; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.; Department of Pediatrics, Augusta University, Augusta, Georgia, USA., Ramaswamy V; Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada., Ring E; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.; Department of Pediatrics, Augusta University, Augusta, Georgia, USA., Rojiani A; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.; Department of Pathology, Augusta University, Augusta, Georgia, USA., Sadek RF; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.; Department of Population Health Sciences, Augusta University, Augusta, Georgia, USA., Satpathy S; Department of Pediatrics, Emory University, Atlanta, Georgia, USA.; Department of Biomedical Informatics, Emory University, Atlanta, Georgia, USA., Schniederjan M; Children's Healthcare of Atlanta and Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA., Smith A; Department of Pediatrics, Arnold Palmer Hospital for Children, Orlando, Florida, USA., Smith C; Lumos Pharma, Inc. (formerly NewLink Genetics Corporation), Austin, Texas, USA., Thomas BE; Department of Pediatrics, Emory University, Atlanta, Georgia, USA., Vaizer R; Department of Pediatrics, Augusta University, Augusta, Georgia, USA., Yeo KK; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA., Bhasin MK; Aflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA.; Department of Pediatrics, Emory University, Atlanta, Georgia, USA.; Department of Biomedical Informatics, Emory University, Atlanta, Georgia, USA., Munn DH; Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.; Department of Pediatrics, Augusta University, Augusta, Georgia, USA.
المصدر:	Neuro-oncology [Neuro Oncol] 2024 Feb 02; Vol. 26 (2), pp. 348-361.
نوع المنشور:	Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE
أسماء مطبوعة:	Publication: 2010- : Oxford : Oxford University Press Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub.,
مواضيع طبية MeSH:	Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain Stem Neoplasms*/pathology, Humans ; Child ; Temozolomide ; Tryptophan ; Immunologic Factors ; Immunotherapy
مستخلص:	Background: Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy. Methods: We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing. Results: Eighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39-77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2-62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7-29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4-61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2-62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype. Conclusions: Indoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
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معلومات مُعتمدة:	Lumos Pharma, Inc.; Alex's Lemonade Stand Foundation; Cannonball Kids' cancer Foundation; Eli's Block Party Childhood Cancer Foundation; Hyundai Hope on Wheels Foundation; Miriam Lloyd Halsey Foundation; Northern Nevada Children's Cancer Foundation; Trial Blazers for Kids Foundation; Press On Foundation
فهرسة مساهمة:	Keywords: IDO; brain cancer; immunotherapy; indoximod; pediatric
سلسلة جزيئية:	ClinicalTrials.gov NCT02502708
المشرفين على المادة:	XD0FY1J13B (1-methyltryptophan) YF1K15M17Y (Temozolomide) 8DUH1N11BX (Tryptophan) 0 (Immunologic Factors)
تواريخ الأحداث:	Date Created: 20230916 Date Completed: 20240205 Latest Revision: 20240229
رمز التحديث:	20240229
مُعرف محوري في PubMed:	PMC10836763
DOI:	10.1093/neuonc/noad174
PMID:	37715730
قاعدة البيانات:	MEDLINE

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تدمد:	1523-5866
DOI:	10.1093/neuonc/noad174