| Autor: |
Anne Rogiers, Pieter Theuns, Hendrik Everaert, Bart Neyns, Johnny Duerinck, Anne Van Binst, Stephanie Du Four, Jennifer De Cremer, Lailia Ben Salama |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Popis: |
Recurrent glioblastoma is a devastating disease for which no treatment has demonstrated to improve overall survival in a randomized clinical trial. Anti-tumor Cytolytic T-cell (CTL) activity is suppressed by the CTLA4 and PD-1 immune-checkpoint receptors. Nivolumab(NIVO) is an IgG-4 mAb that blocks PD-1, and ipilimumab(IPI) an IgG-1 mAb that blocks CTLA-4. In a clinical trial for recurrent glioblastoma (BMS CheckMate143), combination of NIVO and IPI administered IV caused unacceptable toxicity. Animal models showed that intratumoral administration of CTLA-4-blocking mAb at a ratio of [1:100] compared to IV-dosing had equivalent anti-tumor effect and was associated with improved tolerability. An ongoing phase I clinical trial for patients with recurrent glioblastoma (rGB) has currently recruited 5 patients: 2M, 3F, median age 60 (range 38-72). Study treatment consists of surgical resection of rGB with injection of IPI (10mg:2ml) (cohort 1 = first 3 patients) or IPI (5mg:1ml) plus NIVO (10mg:1ml) (cohort 2 = 2 patients at present) in the walls of the resection cavity, concomitant with biweekly IV-administration of 10 mg of NIVO x6. Grade 3 AE consisted of epileptic seizures (1pt in cohort 2) and hemiplegia due to accumulation of serosanguinous fluid in the resection cavity (1pt in cohort 2). Additionally, 4/5 patients developed transient grade 1 pyrexia during the postoperative period. Lymphopenia gr 3 was seen in 4/5 patients. All patients have persisting rim-contrast enhancement on MRI. After median follow-up of 22weeks, two patients have progression of disease (after respectively 13 and 19 weeks). All patients are alive. We conclude from these early results that surgical resection of rGB combined with direct intracerebral injection of IPI alone/with NIVO followed by IV administration of NIVO at the doses administered in this trial is feasible and safe. Updated results of this ongoing clinical trial will be presented at the meeting. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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