Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial
| العنوان: | Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial |
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| المؤلفون: | Elizabeth A. Maher, Benjamin M. Ellingson, Sung Choe, Saewon Chun, Marta Penas-Prado, Hua Liu, Lori Steelman, Patrick Y. Wen, Jennifer Clarke, Ingo K. Mellinghoff, Katherine B. Peters, Robert J. Young, Shuchi Sumant Pandya, Min Lu, Timothy F. Cloughesy, Howard A. Burris, Macarena I. de la Fuente, Filip Janku, Kha Le, Gregory M. Cote, Islam Hassan |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research, vol 27, iss 16 Clin Cancer Res |
| بيانات النشر: | American Association for Cancer Research (AACR), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, IDH1, Adolescent, Pyridines, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, Diamines, IDH2, Article, Young Adult, Rare Diseases, Clinical Research, Glioma, Internal medicine, Humans, Medicine, Oncology & Carcinogenesis, Aged, Cancer, Brain Neoplasms, business.industry, Neurosciences, Middle Aged, medicine.disease, Isocitrate Dehydrogenase, Confidence interval, Brain Disorders, Brain Cancer, Orphan Drug, Isocitrate dehydrogenase, 6.1 Pharmaceuticals, Mutation, Toxicity, Cohort, Disease Progression, Elevated transaminases, Female, Neoplasm Recurrence, Local, business |
| الوصف: | Purpose: Lower grade gliomas (LGGs) are malignant brain tumors. Current therapy is associated with short- and long-term toxicity. Progression to higher tumor grade is associated with contrast enhancement on MRI. The majority of LGGs harbor mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1/IDH2). Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes. Patients and Methods: We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy. Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment is complete; this trial is registered with ClinicalTrials.gov, NCT02481154. Results: Vorasidenib showed a favorable safety profile in the glioma cohort. Dose-limiting toxicities of elevated transaminases occurred at doses ≥100 mg and were reversible. The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG in patients with nonenhancing glioma was 18% (one partial response, three minor responses). The median progression-free survival was 36.8 months [95% confidence interval (CI), 11.2–40.8] for patients with nonenhancing glioma and 3.6 months (95% CI, 1.8–6.5) for patients with enhancing glioma. Exploratory evaluation of tumor volumes in patients with nonenhancing glioma showed sustained tumor shrinkage in multiple patients. Conclusions: Vorasidenib was well tolerated and showed preliminary antitumor activity in patients with recurrent or progressive nonenhancing mIDH LGG. |
| وصف الملف: | application/pdf |
| تدمد: | 1557-3265 1078-0432 0248-1154 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ac86539fe4e5156e90351b80f2f304fTest https://doi.org/10.1158/1078-0432.ccr-21-0611Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2ac86539fe4e5156e90351b80f2f304f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 02481154 |
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