Retifanlimab with Bevacizumab and Hypofractionated Radiotherapy for the Treatment of Recurrent Glioblastoma

Description

PRIMARY OBJECTIVE:

I. To investigate the overall survival at 9 months (OS-9) of the combination of retifanlimab, bevacizumab and hypofractionated radiation therapy (HFRT) vs. the control group treated with bevacizumab and HFRT.

SECONDARY OBJECTIVES:

I. To assess the overall survival (OS) in this patient population for each regimen.

II. To assess the progression free survival (PFS) in this patient population for each regimen.

III. To assess the objective response rate (ORR) in this patient population for each regimen.

IV. To assess the neurologic function by Neurologic Assessment in Neuro-Oncology (NANO) in this patient population for each regimen.

V. To assess the frequency and severity of adverse events in this patient population for each regimen.

CORRELATIVE OBJECTIVE:

I. To assess the anti-glioma immune response before and after retifanlimab including assessment of immune cells phenotyping, function and activation in the pre-/post-treatment blood, and changes in cytokine levels over time.

OUTLINE: Patients are randomized to 1 of 2 arms

ARM A: Patients receive retifanlimab intravenously (IV) over 30 minutes on day 1 and bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT once daily (QD), starting in cycle 1 on day 15 for 10 treatments. Patients undergo magnetic resonance imaging (MRI) or computed tomography (CT), as well as blood sample collection throughout the study.

ARM B: Patients receive bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days. Survival follow-up is every 2 months for the first year, and then every 6 months for up to 4 years from registration.