The objective of this study is to determine response rates (partial and complete responses) to nivolumab of recurrent or progressive IDH mutant (grades 2, 3 or 4) gliomas with prior exposure to alkylating agents.
Gliomas are the most common malignant primary brain tumor in adults. Their clinical presentation is heterogeneous and prognosis is dependent on both the grade of the tumor and the molecular subtype. Somatic mutations in Isocitrate dehydrogenase 1 (IDH1) or, less commonly, Isocitrate dehydrogenase 2 (IDH2) genes have emerged as an important prognostic factor in gliomas and are associated with longer survival. Regardless of initial grade, recurrence and transformation into higher grade tumors is almost universal. There is high unmet medical need in treating recurrent gliomas as there is currently no established standard of care therapy. Recent trials of IDH inhibitors in IDH mutant gliomas and programmed cell death protein 1 (PD-1) and PD-L1 inhibitors in recurrent gliomas have been disappointing. Multiple studies in other cancers have demonstrated that hypermutated tumors are associated with response to immunotherapeutic agents, including anti-CTLA4 agents in melanoma, anti-PD1 therapy in bladder cancer, and anti-programmed-cell-death protein 1 (anti-PD1) therapy in lung, and colorectal cancer. There is evidence to suggest that gliomas with somatic IDH mutations are more prone to develop hypermutation after exposure to alkylating agents than IDH wildtype tumors, providing strong scientific rationale for establishing nivolumab as a treatment option in this subgroup of patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Nivolumab (Opdivo®) is a human monoclonal antibody (HuMAb; immunoglobulin G4 (IgG4)- S228P) that targets the PD-1 cluster of differentiation 279 (CD279) cell surface membrane receptor.
Miami Cancer Center
Miami, Florida, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Columbia University Medical Center
New York, New York, United States
Weill Cornell Medical College
New York, New York, United States
Overall Response Rate
The overall response rate is defined as the percentage of patients with a reduction in tumor size while on treatment.
Time frame: Throughout treatment duration or until progressive disease, unacceptable toxicity, or withdrawal of consent, up to 2 years
Duration of Response
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time frame: Until the first date that progressive disease is objectively documented or until study completion (36 months)
Progression-Free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Participants discontinuing study treatment will remain on study for documentation of progression and death.
Time frame: Until death or study completion (36 months)
Overall Survival (OS)
OS is defined as the time from the first dose of nivolumab to death due to any cause. All other participants will be censored at the last date known to be alive.
Time frame: Until death or study completion (36 months)
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