Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma.
Abstract | BACKGROUND: METHODS: In this multicenter phase I study, patients received 0.5-3.2 mg/kg ABT-414 every 2 weeks by intravenous infusion. EGFR alterations, O6-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation, and isocitrate dehydrogenase (IDH1) gene mutations were assessed in patient tumors. Distinct prognostic classes were assigned to patients based on a Molecular Classification Predictor model. RESULTS: As of January 7, 2016, forty-five patients were enrolled to receive ABT-414 plus radiation and temozolomide. The most common treatment emergent adverse events were ocular: blurred vision, dry eye, keratitis, photophobia, and eye pain. Ocular toxicity at any grade occurred in 40 patients and at grades 3/4 in 12 patients. RPTD and MTD were set at 2 mg/kg and 2.4 mg/kg, respectively. Among 38 patients with pretreatment tumor tested centrally, 39% harbored EGFR amplification, of which 73% had EGFRvIII mutation. Among patients with available tumor tissue ( n = 30), 30% showed MGMT promoter methylation and none had IDH1 mutations. ABT-414 demonstrated an approximately dose proportional pharmacokinetic profile. The median duration of progression-free survival was 6.1 months; median overall survival has not been reached. CONCLUSION:
ABT-414 plus chemoradiation demonstrated an acceptable safety and pharmacokinetic profile in newly diagnosed glioblastoma. Randomized studies are ongoing to determine efficacy in newly diagnosed (NCT02573324) and recurrent glioblastoma (NCT02343406).
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Authors | David A Reardon, Andrew B Lassman, Martin van den Bent, Priya Kumthekar, Ryan Merrell, Andrew M Scott, Lisa Fichtel, Erik P Sulman, Erica Gomez, JuDee Fischer, Ho-Jin Lee, Wijith Munasinghe, Hao Xiong, Helen Mandich, Lisa Roberts-Rapp, Peter Ansell, Kyle D Holen, Hui K Gan |
Journal | Neuro-oncology
(Neuro Oncol)
Vol. 19
Issue 7
Pg. 965-975
(Jul 01 2017)
ISSN: 1523-5866 [Electronic] England |
PMID | 28039367
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
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Copyright | © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected] |
Chemical References |
- ABT-414
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Biomarkers, Tumor
- Immunoconjugates
- Dacarbazine
- Temozolomide
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal, Humanized
(pharmacology, therapeutic use)
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Biomarkers, Tumor
(metabolism)
- Brain Neoplasms
(drug therapy, radiotherapy)
- Dacarbazine
(analogs & derivatives, pharmacology, therapeutic use)
- Disease-Free Survival
- Drug Therapy, Combination
- Female
- Glioblastoma
(drug therapy, radiotherapy)
- Humans
- Immunoconjugates
(pharmacology, therapeutic use)
- Male
- Maximum Tolerated Dose
- Middle Aged
- Temozolomide
- Treatment Outcome
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