The purpose of this study is to assess the safety/tolerability/feasibility of pembrolizumab and radiation therapy before surgical resection in patients with recurrent glioblastoma as defined by treatment-related AEs and the number of patients who do not necessitate a delay in surgical resection, and to assess overall survival. The secondary objectives are to assess progression free survival, and to assess the T cell clonality, CD8 T cell activation and Tumor Infiltrating Lymphocyte (TIL) score after treatment
Age 18 years or older
Confirmed histologic diagnosis of WHO Grade IV, Glioblastoma Multiforme
GBM recurrence or progression with planned standard of care surgical resection and repeat radiation
Tumor size less than 6 cm
Contraindication to additional radiation
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
Immunodeficiency diagnosis or receiving chronic systemic steroid therapy (exceeding 10 mg daily of prednisone) or any other form of immunosuppressive therapy
Severe hypersensitivity to pembrolizumab
Single group
Pembrolizumab
DrugPembrolizumab 400mg administered intravenously on Day 1, and then beginning 6 weeks post-surgery, subjects will receive 400 mg pembrolizumab every 6 weeks
Stereotactic Radiation Therapy
RadiationStandard of care stereotactic radiation of 24 grays over 3 days, administered beginning on Day 7
Surgical Resection
Procedure/SurgeryStandard of care surgical resection of tumor on Day 10-28
Safety and tolerability measured by the incidence of adverse events, serious adverse events and grade 3 or above treatment related adverse events.
Safety and tolerability measured by the incidence of adverse events, serious adverse events and grade 3 or above treatment related adverse events as assessed per CTCAE, Version 5.0.
Overall survival
From start of study treatment until death, loss to follow-up, or withdrawal of consent. Subjects who are lost to survival follow-up will not be replaced, and public records may be accessed to assess Overall Survival.
Progression free survival
From start of study treatment until confirmation of disease progression (per iRANO Criteria), intolerable toxicities, withdrawal of consent, or up to 2 years or 18 cycles of pembrolizumab, whichever comes first.
Immune action
To assess the T cell clonality, CD8 T cell activation and Tumor Infiltrating Lymphocyte (TIL) score after treatment. Blood draws for research purposes performed after obtaining consent but prior to neoadjuvant pembrolizumab administration, and at the time of initiation of SRT and at the time of surgery
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Chirag G. Patil
Lead sponsor
Cedars-Sinai Medical Center
Sponsor institution
Merck Sharp & Dohme LLC
Collaborator
National Cancer Institute (NCI)
Collaborator
