Phase I study of PD-L1 inhibition with avelumab and laser interstitial thermal therapy in patients with recurrent glioblastoma.

Abstract

TPS2074 Background: Glioblastoma (GBM) the most frequent malignant brain tumor in the adult has a dismal prognosis and limited treatment options. Current advances have highlighted how tumors and specifically GBM evade the immune system by exploiting the mechanisms of tolerance and inducing local and systemic immunosuppression. Another hurdle in the treatment of GBM is the blood-brain barrier (BBB). Recent work suggests that MRI-guided laser interstitial thermal therapy (LITT) can increase the permeability of the BBB and may have an abscopal effect. Therefore, utilizing MRI-guided LITT, a potential immunogenic cell death-inducing procedure that disrupts the BBB and makes Avelumab a PD-L1 monoclonal antibody being more accessible to GBM tumors, seem a valid approach for immunomodulation and successful implementation of a combined regimen to treat brain cancer. Methods: This is a prospective non-randomized open label to characterize the tolerability and safety profile of Avelumab in combination with LITT in patients with recurrent glioblastoma who were treated with radiation therapy with concurrent Temozolomide chemotherapy at diagnosis, and whose tumor at recurrence measures less then 3 cm3. Avelumab is administered within a week after real-time MRI-guided LITT therapy and every 2 weeks thereafter. On part A patients are treated with intravenous Avelumab alone and on part B patients receive Avelumab in combination with MRI-guided LITT. Part A completed enrollment without DLT. Enrollment on part B began in October 2018. A Simon minimax two-stage design is being used for efficacy. Toxicity will be scored using the NCI-CTCAE 4.03 criteria. Blood samples and tumor tissue will be collected for correlative studies. Quantification of the changes in inflammatory and immunosuppressive profiles across time points for patients receiving treatment with Avelumab will be obtained. This information will instruct future immunotherapy approaches to treat GBM and the rational for those combinations. Clinical trial information: NCT03341806.