دورية أكاديمية
ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma.
| العنوان: | ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma. |
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| المؤلفون: | Arrillaga-Romany I; Massachusetts General Hospital, Boston, MA., Gardner SL; New York University, Grossman School of Medicine, New York, NY., Odia Y; Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL., Aguilera D; Children's Healthcare of Atlanta, Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA., Allen JE; Chimerix, Inc, Durham, NC., Batchelor T; Dana-Farber/Brigham and Women's Cancer Center, Boston, MA., Butowski N; University of California, San Francisco, CA., Chen C; University of Minnesota Medical Center, Minneapolis, MN., Cloughesy T; University of California, Los Angeles, CA., Cluster A; Washington University of St Louis, St Louis, MO., de Groot J; University of California, San Francisco, CA., Dixit KS; Northwestern Medical Lou and Jean Malnati Brain Tumor Institute, Chicago, IL., Graber JJ; University of Washington Medical Center, Seattle, WA., Haggiagi AM; Columbia University Irving Medical Center, New York, NY., Harrison RA; BC Cancer, The University of British Columbia, Vancouver, BC, Canada., Kheradpour A; Loma Linda University, Loma Linda, CA., Kilburn LB; Children's National Hospital, Washington, DC., Kurz SC; University Hospital Tuebingen, Tuebingen, Germany., Lu G; Oncoceutics Inc, Philadelphia, PA., MacDonald TJ; Children's Healthcare of Atlanta, Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA., Mehta M; Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL., Melemed AS; Chimerix, Inc, Durham, NC., Nghiemphu PL; University of California, Los Angeles, CA., Ramage SC; Chimerix, Inc, Durham, NC., Shonka N; University of Nebraska Medical Center, Omaha, NE., Sumrall A; Levine Cancer Institute, Charlotte, NC., Tarapore RS; Chimerix, Inc, Durham, NC., Taylor L; University of Washington Medical Center, Seattle, WA., Umemura Y; University of Michigan, Ann Arbor, MI., Wen PY; Dana-Farber/Brigham and Women's Cancer Center, Boston, MA. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 May 01; Vol. 42 (13), pp. 1542-1552. Date of Electronic Publication: 2024 Feb 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Glioma*/genetics , Glioma*/drug therapy , Glioma*/pathology , Brain Neoplasms*/genetics , Brain Neoplasms*/drug therapy , Brain Neoplasms*/pathology , Mutation* , Histones*/genetics, Humans ; Adult ; Female ; Male ; Adolescent ; Middle Aged ; Young Adult ; Child ; Aged ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/drug therapy ; Child, Preschool ; Pyrimidines/therapeutic use ; Pyrimidines/adverse effects ; Pyridones/therapeutic use |
| مستخلص: | Purpose: Histone 3 (H3) K27M-mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. This integrated analysis evaluated single-agent ONC201 (dordaviprone), a first-in-class imipridone, in recurrent H3 K27M-mutant DMG. Methods: Fifty patients (pediatric, n = 4; adult, n = 46) with recurrent H3 K27M-mutant DMG who received oral ONC201 monotherapy in four clinical trials or one expanded access protocol were included. Eligible patients had measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma (HGG) criteria and performance score (PS) ≥60 and were ≥90 days from radiation; pontine and spinal tumors were ineligible. The primary end point was overall response rate (ORR) by RANO-HGG criteria. Secondary end points included duration of response (DOR), time to response (TTR), corticosteroid response, PS response, and ORR by RANO low-grade glioma (LGG) criteria. Radiographic end points were assessed by dual-reader, blinded independent central review. Results: The ORR (RANO-HGG) was 20.0% (95% CI, 10.0 to 33.7). The median TTR was 8.3 months (range, 1.9-15.9); the median DOR was 11.2 months (95% CI, 3.8 to not reached). The ORR by combined RANO-HGG/LGG criteria was 30.0% (95% CI, 17.9 to 44.6). A ≥50% corticosteroid dose reduction occurred in 7 of 15 evaluable patients (46.7% [95% CI, 21.3 to 73.4]); PS improvement occurred in 6 of 34 evaluable patients (20.6% [95% CI, 8.7 to 37.9]). Grade 3 treatment-related treatment-emergent adverse events (TR-TEAEs) occurred in 20.0% of patients; the most common was fatigue (n = 5; 10%); no grade 4 TR-TEAEs, deaths, or discontinuations occurred. Conclusion: ONC201 monotherapy was well tolerated and exhibited durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG. |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT03416530; NCT03295396; NCT05392374; NCT03134131; NCT02525692 |
| المشرفين على المادة: | 0 (Histones) 0 (Pyrimidines) 0 (Pyridones) |
| تواريخ الأحداث: | Date Created: 20240209 Date Completed: 20240426 Latest Revision: 20240517 |
| رمز التحديث: | 20240517 |
| مُعرف محوري في PubMed: | PMC11095894 |
| DOI: | 10.1200/JCO.23.01134 |
| PMID: | 38335473 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
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| DOI: | 10.1200/JCO.23.01134 |