PHASE IB STUDY OF AVELUMAB WITH RADIOTHERAPY IN PATIENTS WITH LEPTOMENINGEAL DISEASE

A phase IB, single-arm, non-randomized study to establish the safety of the PDL-1 inhibitor Avelumab with radiotherapy in patients with leptomeningeal disease (LMDz) from metastatic melanoma, lung cancer, and breast cancer. We hypothesize 1) systemic Avelumab will activate peripheral T cells and, with whole-brain radiotherapy (to induce blood-brain-barrier breakdown and stimulate antigen expression), significantly increase the number and activation status of T cells that migrate into the cerebrospinal fluid (CSF), with an Inflammatory CSF cytokine profile, in patients with LMDz; 2) this treatment regime is safe and tolerated without significant toxicities and will improve overall survival compared to historical controls; and 3) point estimates (with confidence intervals) can be derived using CSF measurements, toxicities, and clinical benefit to estimate sample sizes/schedules for an expanded Recommended Phase II Study. Overall design: A maximum of 15 individuals with any cancer that is not hematologic and leptomeningeal disease, being treated at Moffitt Cancer Center, Tampa, Florida. This is a Phase 1b study with safety evaluated continuously. I = initial sample. E = endpoint sample.