دورية أكاديمية
Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial.
العنوان: | Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial. |
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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.) |
References: | Trends Immunol. 2016 Mar;37(3):193-207. (PMID: 26839260) Tumori. 2021 Aug;107(4):276-281. (PMID: 33877022) Cancer Discov. 2021 Jun;11(6):1353-1367. (PMID: 33712487) Eur J Cancer. 2021 Jun;150:53-62. (PMID: 33892407) Clin Cancer Res. 2014 Oct 15;20(20):5290-301. (PMID: 24691018) Amino Acids. 2010 Jul;39(2):565-78. (PMID: 20140689) Proc Natl Acad Sci U S A. 2018 Mar 27;115(13):3249-3254. (PMID: 29531094) Oncotarget. 2016 Apr 19;7(16):22928-38. (PMID: 27008709) Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):1541-8. (PMID: 22245198) Acta Neuropathol. 2017 Nov;134(5):705-714. (PMID: 28733933) Clin Pharmacol Ther. 2020 Dec;108(6):1274-1288. (PMID: 32564368) Radiother Oncol. 2015 Aug;116(2):301-8. (PMID: 26243681) Cancer. 2007 Oct 1;110(7):1542-50. (PMID: 17705175) Lancet Oncol. 2020 Jun;21(6):e317-e329. (PMID: 32502458) J Immunother Cancer. 2021 Jun;9(6):. (PMID: 34117113) Immunity. 2021 Oct 12;54(10):2354-2371.e8. (PMID: 34614413) Lancet Oncol. 2021 Oct;22(10):e456-e465. (PMID: 34592195) Nature. 2021 Aug;596(7870):126-132. (PMID: 34290408) Cancer. 2014 Dec 1;120(23):3731-7. (PMID: 25080363) Pediatr Blood Cancer. 2014 Apr;61(4):636-42. (PMID: 24123865) J Immunother Cancer. 2014 Jul 07;2:21. (PMID: 25054064) Sci Adv. 2019 Nov 27;5(11):eaav9879. (PMID: 31807694) Neuro Oncol. 2014 May;16(5):748-53. (PMID: 24482446) FEBS J. 2022 Oct;289(20):6099-6118. (PMID: 34145969) Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3909-14. (PMID: 22355111) Front Oncol. 2021 Jun 08;11:660892. (PMID: 34168987) Pediatr Blood Cancer. 2021 Feb;68(2):e28756. (PMID: 33025730) Lancet Oncol. 2019 Aug;20(8):1083-1097. (PMID: 31221619) J Immunol. 2004 Apr 1;172(7):4100-10. (PMID: 15034022) Lancet Oncol. 2020 Jun;21(6):e330-e336. (PMID: 32502459) Cancer Res. 2007 Jan 15;67(2):792-801. (PMID: 17234791) Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20828-33. (PMID: 19088199) Cell. 2019 Jun 13;177(7):1888-1902.e21. (PMID: 31178118) J Neurooncol. 2018 Mar;137(1):83-92. (PMID: 29236237) Nat Med. 2022 Jan;28(1):125-135. (PMID: 34992263) Nature. 2020 Mar;579(7798):274-278. (PMID: 32103181) N Engl J Med. 2022 Jun 2;386(22):2112-2119. (PMID: 35648703) Orphanet J Rare Dis. 2020 Mar 12;15(1):69. (PMID: 32164754) Future Oncol. 2020 Jan;16(2):4359-4368. (PMID: 31823654) |
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 |
تدمد: | 1523-5866 |
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DOI: | 10.1093/neuonc/noad174 |