IT-11A PHASE I/ II CLINICAL TRIAL OF CT-011 (PIDILIZUMAB) IN DIFFUSE INTRINSIC PONTINE GLIOMA AND RELAPSED HIGH GRADE GLIOMA: A PRELIMINARY REPORT

摘要

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) and relapsed high grade glioma (HGG) are incurable diseases with an event free survival of 6-8 months. Anti-Programmed Death 1 (anti-PD1) antibodies have recently emerged as a promising treatment modality in multiple cancer types. Clinical studies evaluating anti PD1 antibodies in the setting of primary brain tumors have not yet been reported. Pidilizumab (CureTech, Yavne, Israel) is an anti- PD1 humanized immunoglubulin G1 monoclonal antibody. This investigator-initiated clinical trial evaluates pidilizumab in malignant gliomas (). METHODS: Patients older than 3 years treated with not more than 2mg/M2 of dexamethasone per day are included. Patients with newly diagnosed DIPG are recruited for biweekly pidilizumab within the first month after completion of radiotherapy. Patients with HGG relapsed after standard treatment are recruited for biweekly pidilizumab as an add-on therapy to bevacizumab within 3 months of recurrence. The study was opened in February 2014. RESULTS: To date, 6 patients have been enrolled: three with newly diagnosed DIPG, two with HGG and one with relapsed DIPG (bevacizumab + pidilizumab). A total of 30 cycles of Pidilizumab (range 2- 14) have been administered. Treatment was well tolerated with transient fatigue as the main side effect. Administration of pidilizumab less than 10 days after bevacizumab resulted in a grade 3 blood pressure elevation in one patient. This did not recur when the interval between agents was increased. One patient withdrew because of parents' decision. One patient with HGG progressed and died within 2.5 months from enrollment. Two patients had a significant tumor shrinkage along with clinical improvement. Scheduled imaging evaluation is pending in the rest. CONCLUSION: The trial is ongoing. This report is confined to schedule and initial enrollment results.