Approximately 200,00 patients are diagnosed with brain metastasis in the United States annually, comprising about 10% of all cancer patients. Furthermore, approximately 100,000 patients die from brain metastasis each year, meaning that 20-50% of patients dying from cancer have brain metastases. The brain was once considered “immunologically privileged” meaning it could selectively block the entry of immune cells to limit inflammation in the brain. However, it has been demonstrated that brain tumors may increase the permeability of immune cells into the blood-brain barrier. Although, the anticancer potential of these immune cells is thwarted by the infiltration of immunosuppressive cells and adaptive mechanisms cancer cells use to evade immune cells. Pembrolizumab, an immune checkpoint inhibitor that targets PD-1, blocks these protective mechanisms, essentially unhiding cancer cells from immune cells, increasing the antitumor activity. Preclinical data has also shown that lenvatinib, a drug that targets VEGF, may promote an immune permissive environment by reversing VEGF-mediated immune suppression, thereby enhancing the activity of pembrolizumab. This phase II study will assess the overall response rate of pembrolizumab in combination with lenvatinib in patients with brain metastases.
Trial Registration: ClinicalTrials.gov Identifier: NCT05064280