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ATIM-15. A PHASE I TRIAL OF HYPOFRACTIONATED STEREOTACTIC IRRADIATION (HFSRT) WITH PEMBROLIZUMAB AND BEVACIZUMAB IN patients with recurrent high grade gliomas

2016; Oxford University Press; Volume: 18; Issue: suppl_6 Linguagem: Inglês

10.1093/neuonc/now212.080

1523-5866

Solmaz Sahebjam, Peter A.S. Johnstone, Peter Forsyth, John A. Arrington, Michael Jaglal, Nam Tran, Frank D. Vrionis, Arnold B. Etame, Melissa Wicklund, A Elie, Tyra Gatewood, Robert J.B. Macaulay, Prakash Chinnaiyan, Michael Yu,

Radiomics and Machine Learning in Medical Imaging

High grade gliomas carry a grim prognosis despite current therapies. Expression of PD-1 and PD-L1 is found in the microenvironment of most high grade gliomas. There is strong pre-clinical evidence for the combination of anti PD-1/PD-L1 blockade with radiotherapy and anti-angiogenic agents. This study evaluates the combination of pembrolizumab, an anti-PD-1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab. This phase I study (3+3 design) explores the safety, tolerability, recommended phase II dose (RP2D), and antitumor activity of pembrolizumab administered concurrently with HFSRT and bevacizumab (NCT02313272). Adult patients with recurrent glioblastoma (GBM) or anaplastic astrocytoma (maximum diameter of target lesion ≤ 3.5 cm) are eligible. Eligible patients receive HFSRT to the recurrent tumor (30 Gy delivered in 5 fractions) combined with bevacizumab (10 mg/kg, intravenously Q2W) and pembrolizumab (100 mg or 200 mg intravenously based on dose level, Q3W). Two dose levels of pembrolizumab (100 mg and 200 mg Q3W) are explored. After determination of RP2D, an additional 20 patients will be enrolled in an expansion cohort. Response is assessed every 6W per RANO criteria. Effect of treatment on quality of life measures are evaluated. As of June 2016, dose escalation cohort has been completed and accrual to dose expansion cohort is ongoing. Combination of HFSRT (30 Gy in 5 fractions) with pembrolizumab (200 mg every 3 weeks) and bevacizumab (10 mg/kg every 2 weeks) is well tolerated. No dose limiting toxicity or treatment-related neurologic adverse event has been observed. Six out of nine patients have achieved objective response (complete response + partial response). Preliminary data demonstrate an acceptable toxicity profile and encouraging anti-tumor activity. Updated safety and efficacy data will be presented.