Early trial finds promise for avelumab and radiation in treating leptomeningeal disease

Researchers at Moffitt Cancer Center have reported encouraging results from a phase 1B clinical trial showing that the immunotherapy drug avelumab, when combined with whole brain radiotherapy, may provide a safe and effective treatment option for patients with leptomeningeal disease, one of the most aggressive and difficult-to-treat complications of advanced cancer. The findings were published in Neuro-Oncology. 

Leptomeningeal disease occurs when cancer cells spread to the membranes surrounding the brain and spinal cord. Patients typically survive only a few weeks to months after diagnosis. Few prospective clinical trials have been conducted in this setting and treatment options remain limited. 

The study enrolled 15 patients with leptomeningeal disease from breast, lung, ovarian, pancreatic and other solid tumors. Patients received avelumab before, during and after whole brain radiotherapy. 

Key findings include: 

• Survival benefit: 67% of patients were alive three months after treatment, with some surviving more than a year. 

• Safety: Side effects were manageable. No treatment-related deaths occurred. 

• Immune activity: Analysis of cerebrospinal fluid showed that treatment stimulated an adaptive immune response, reducing levels of regulatory T cells and altering immune checkpoint activity in CD8+ T cells and macrophages. 

Patients with leptomeningeal disease face some of the poorest outcomes in oncology. Our trial shows that combining immunotherapy with radiation is safe and has signs of clinical benefit. These results set the stage for larger studies that could ultimately change the treatment landscape for this patient population." 

Yolanda Piña, M.D., neuro-oncologist at Moffitt and the study's lead author

Peter Forsyth, M.D., chair of Moffitt's Neuro-Oncology Department and senior author of the study, emphasized the importance of the translational findings. 

"By analyzing cerebrospinal fluid before and after treatment, we gained valuable insight into how the immune system responds," Forsyth said. "This work points to new therapeutic strategies, including targeting immune checkpoints like LAG3, to overcome resistance." 

The researchers note that while the study was small and designed primarily to assess safety, the survival outcomes and immune findings support moving forward with a phase 2 trial. 

This study was supported by Pfizer and was previously conducted under an alliance between the health care business of Merck KGaA and Pfizer. It was also supported by the National Cancer Institute (R21CA256289, P30-CA076292) and the Florida Department of Health Bankhead-Coley Program (24B04).