Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas
Priscilla K. Brastianos, Albert E. Kim, Anita Giobbie‐Hurder, Eudocia Q. Lee, Nancy Wang, April F. Eichler, Ugonma Chukwueke, Deborah Forst, Isabel Arrillaga‐Romany, Jörg Dietrich, Zachary Corbin, Jennifer Moliterno, Joachim M. Baehring, Michael G. White, Kevin Lou, Juliana M. Larson, Magali de Sauvage, Kathryn Evancic, Joana L. Mora, Naema Nayyar, Jay S. Loeffler, Kevin Oh, Helen A. Shih, William T. Curry, Daniel P. Cahill, Fred G. Barker, Elizabeth R. Gerstner, Sandro Santagata
Abstract
High-grade meningiomas are associated with neuro-cognitive morbidity and have limited treatments. High-grade meningiomas harbor an immunosuppressive tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression may contribute to their aggressive phenotype. Here, we present the results of a single-arm, open-label phase 2 trial (NCT03279692) evaluating the efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 25 evaluable patients with recurrent and progressive grade 2 and 3 meningiomas. The primary endpoint is the proportion of patients alive and progression-free at 6 months (PFS-6). Secondary endpoints include progression-free and overall survival, best intracranial response, and toxicity. Our study has met its primary endpoint and achieved a PFS-6 rate of 0.48 (90% exact CI: 0.31-0.66) and a median PFS of 7.6 months (90% CI: 3.4-12.9 months). Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that pembrolizumab exerts promising efficacy on a subset of these tumors. Further studies are needed to identify the biological facets within the meningioma TME that may drive response to immune-based therapies.